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1
Parry, Christopher M., Nguyen Minh Duong, Jiaji Zhou, Nguyen Thi Hoang Mai, To Song Diep, Le Quoc Thinh, John Wain, et al. "Emergence in Vietnam of Streptococcus pneumoniae Resistant to Multiple Antimicrobial Agents as a Result of Dissemination of the Multiresistant Spain23F-1 Clone." Antimicrobial Agents and Chemotherapy 46, no. 11 (November 2002): 3512–17. http://dx.doi.org/10.1128/aac.46.11.3512-3517.2002.
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ABSTRACT Surveillance for Streptococcus pneumoniae resistant to penicillin and other antimicrobial agents is necessary to define the optimal empirical antibiotic therapy for meningitis in resource-poor countries such as Vietnam. The clinical and microbiological features of 100 patients admitted to the Centre for Tropical Diseases in Ho Chi Minh City, Vietnam, between 1993 and 2002 with invasive pneumococcal disease were studied. A penicillin-nonsusceptible pneumococcus (MIC, ≥0.1 μg/ml) was isolated from the blood or cerebrospinal fluid of 8% of patients (2 of 24) between 1993 and 1995 but 56% (20 of 36) during 1999 to 2002 (P < 0.0001). Pneumococcal isolates resistant to penicillin (MIC, ≥2.0 μg/ml) increased from 0% (0 of 24) to 28% (10 of 36) (P = 0.002). Only one isolate was ceftriaxone resistant (MIC, 2.0 μg/ml). Penicillin-nonsusceptible pneumococci were isolated from 78% of children younger than 15 years (28 of 36) compared with 25% of adults (16 of 64) (P = 0.0001). Isolation of a penicillin-nonsusceptible pneumococcus in adults with meningitis was independently associated with referral from another hospital (P = 0.005) and previous antibiotic therapy (P = 0.025). Multilocus sequence typing showed that 86% of the invasive penicillin-resistant pneumococcus isolates tested (12 of 14) were of the Spain23F-1 clone. The serotypes of >95% of the penicillin-nonsusceptible pneumococci were included in the currently available pneumococcal vaccines. Our findings point to the recent introduction and spread of the Spain23F-1 clone of penicillin-resistant pneumococci in Vietnam. Simple clinical predictors can be used to guide empirical antibiotic therapy of meningitis. Pneumococcal vaccination may help to control this problem.
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Wren, John T., Lance K. Blevins, Bing Pang, Lauren B. King, Antonia C. Perez, Kyle A. Murrah, Jennifer L. Reimche, Martha A. Alexander-Miller, and W. Edward Swords. "Influenza A Virus Alters Pneumococcal Nasal Colonization and Middle Ear Infection Independently of Phase Variation." Infection and Immunity 82, no. 11 (August 25, 2014): 4802–12. http://dx.doi.org/10.1128/iai.01856-14.
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ABSTRACTStreptococcus pneumoniae(pneumococcus) is both a widespread nasal colonizer and a leading cause of otitis media, one of the most common diseases of childhood. Pneumococcal phase variation influences both colonization and disease and thus has been linked to the bacteria's transition from colonizer to otopathogen. Further contributing to this transition, coinfection with influenza A virus has been strongly associated epidemiologically with the dissemination of pneumococci from the nasopharynx to the middle ear. Using a mouse infection model, we demonstrated that coinfection with influenza virus and pneumococci enhanced both colonization and inflammatory responses within the nasopharynx and middle ear chamber. Coinfection studies were also performed using pneumococcal populations enriched for opaque or transparent phase variants. As shown previously, opaque variants were less able to colonize the nasopharynx.In vitro, this phase also demonstrated diminished biofilm viability and epithelial adherence. However, coinfection with influenza virus ameliorated this colonization defectin vivo. Further, viral coinfection ultimately induced a similar magnitude of middle ear infection by both phase variants. These data indicate that despite inherent differences in colonization, the influenza A virus exacerbation of experimental middle ear infection is independent of the pneumococcal phase. These findings provide new insights into the synergistic link between pneumococcus and influenza virus in the context of otitis media.
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Hatcher, Brandon L., Joanetha Y. Hale, and David E. Briles. "Free Sialic Acid Acts as a Signal That Promotes Streptococcus pneumoniae Invasion of Nasal Tissue and Nonhematogenous Invasion of the Central Nervous System." Infection and Immunity 84, no. 9 (June 27, 2016): 2607–15. http://dx.doi.org/10.1128/iai.01514-15.
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Streptococcus pneumoniae(pneumococcus) is a leading cause of bacterial meningitis and neurological sequelae in children worldwide. Acute bacterial meningitis is widely considered to result from bacteremia that leads to blood-brain barrier breakdown and bacterial dissemination throughout the central nervous system (CNS). Previously, we showed that pneumococci can gain access to the CNS through a nonhematogenous route without peripheral blood infection. This access is thought to occur when the pneumococci in the upper sinus follow the olfactory nerves and enter the CNS through the olfactory bulbs. In this study, we determined whether the addition of exogenous sialic acid postcolonization promotes nonhematogenous invasion of the CNS. Previously, others showed that treatment with exogenous sialic acid post-pneumococcal infection increased the numbers of CFU recovered from an intranasal mouse model of infection. Using a pneumococcal colonization model, anin vivoimaging system, and a multiplex assay for cytokine expression, we demonstrated that sialic acid can increase the number of pneumococci recovered from the olfactory bulbs and brains of infected animals. We also show that pneumococci primarily localize to the olfactory bulb, leading to increased expression levels of proinflammatory cytokines and chemokines. These findings provide evidence that sialic acid can enhance the ability of pneumococci to disseminate into the CNS and provide details about the environment needed to establish nonhematogenous pneumococcal meningitis.
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Tabusi, Mahebali, Sigrun Thorsdottir, Maria Lysandrou, Ana Rita Narciso, Melania Minoia, Chinmaya Venugopal Srambickal, Jerker Widengren, Birgitta Henriques-Normark, and Federico Iovino. "Neuronal death in pneumococcal meningitis is triggered by pneumolysin and RrgA interactions with β-actin." PLOS Pathogens 17, no. 3 (March 24, 2021): e1009432. http://dx.doi.org/10.1371/journal.ppat.1009432.
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Neuronal damage is a major consequence of bacterial meningitis, but little is known about mechanisms of bacterial interaction with neurons leading to neuronal cell death.Streptococcus pneumoniae(pneumococcus) is a leading cause of bacterial meningitis and many survivors develop neurological sequelae after the acute infection has resolved, possibly due to neuronal damage. Here, we studied mechanisms for pneumococcal interactions with neurons. Using human primary neurons, pull-down experiments and mass spectrometry, we show that pneumococci interact with the cytoskeleton protein β-actin through the pilus-1 adhesin RrgA and the cytotoxin pneumolysin (Ply), thereby promoting adhesion and invasion of neurons, and neuronal death. Using our bacteremia-derived meningitis mouse model, we observe that RrgA- and Ply-expressing pneumococci co-localize with neuronal β-actin. Using purified proteins, we show that Ply, through its cholesterol-binding domain 4, interacts with the neuronal plasma membrane, thereby increasing the exposure on the outer surface of β-actin filaments, leading to more β-actin binding sites available for RrgA binding, and thus enhanced pneumococcal interactions with neurons. Pneumococcal infection promotes neuronal death possibly due to increased intracellular Ca2+levels depending on presence of Ply, as well as on actin cytoskeleton disassembly. STED super-resolution microscopy showed disruption of β-actin filaments in neurons infected with pneumococci expressing RrgA and Ply. Finally, neuronal death caused by pneumococcal infection could be inhibited using antibodies against β-actin. The generated data potentially helps explaining mechanisms for why pneumococci frequently cause neurological sequelae.
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Ullah, Ihsan, Neil D. Ritchie, and Tom J. Evans. "The interrelationship between phagocytosis, autophagy and formation of neutrophil extracellular traps following infection of human neutrophils by Streptococcus pneumoniae." Innate Immunity 23, no. 5 (April 11, 2017): 413–23. http://dx.doi.org/10.1177/1753425917704299.
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Neutrophils play an important role in the innate immune response to infection with Streptococcus pneumoniae, the pneumococcus. Pneumococci are phagocytosed by neutrophils and undergo killing after ingestion. Other cellular processes may also be induced, including autophagy and the formation of neutrophil extracellular traps (NETs), which may play a role in bacterial eradication. We set out to determine how these different processes interacted following pneumococcal infection of neutrophils, and the role of the major pneumococcal toxin pneumolysin in these various pathways. We found that pneumococci induced autophagy in neutrophils in a type III phosphatidylinositol-3 kinase dependent fashion that also required the autophagy gene Atg5. Pneumolysin did not affect this process. Phagocytosis was inhibited by pneumolysin but enhanced by autophagy, while killing was accelerated by pneumolysin but inhibited by autophagy. Pneumococci induced extensive NET formation in neutrophils that was not influenced by pneumolysin but was critically dependent on autophagy. While pneumolysin did not affect NET formation, it had a potent inhibitory effect on bacterial trapping within NETs. These findings show a complex interaction between phagocytosis, killing, autophagy and NET formation in neutrophils following pneumococcal infection that contribute to host defence against this pathogen.
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Prajsnar, Tomasz K., Bartosz J. Michno, Niedharsan Pooranachandran, Andrew K. Fenton, Tim J. Mitchell, David H. Dockrell, and Stephen A. Renshaw. "Phagosomal Acidification Is Required to Kill Streptococcus pneumoniae in a Zebrafish Model." Cellular Microbiology 2022 (June 9, 2022): 1–13. http://dx.doi.org/10.1155/2022/9429516.
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Streptococcus pneumoniae (the pneumococcus) is a major human pathogen causing invasive disease, including community-acquired bacteraemia, and remains a leading cause of global mortality. Understanding the role of phagocytes in killing bacteria is still limited, especially in vivo. In this study, we established a zebrafish model to study the interaction between intravenously administered pneumococci and professional phagocytes such as macrophages and neutrophils, to unravel bacterial killing mechanisms employed by these immune cells. Our model confirmed the key role of polysaccharide capsule in promoting pneumococcal virulence through inhibition of phagocytosis. Conversely, we show pneumococci lacking a capsule are rapidly internalised by macrophages. Low doses of encapsulated S. pneumoniae cause near 100% mortality within 48 hours postinfection (hpi), while 50 times higher doses of unencapsulated pneumococci are easily cleared. Time course analysis of in vivo bacterial numbers reveals that while encapsulated pneumococcus proliferates to levels exceeding 105 CFU at the time of host death, unencapsulated bacteria are unable to grow and are cleared within 20 hpi. Using genetically induced macrophage depletion, we confirmed an essential role for macrophages in bacterial clearance. Additionally, we show that upon phagocytosis by macrophages, phagosomes undergo rapid acidification. Genetic and chemical inhibition of vacuolar ATPase (v-ATPase) prevents intracellular bacterial killing and induces host death indicating a key role of phagosomal acidification in immunity to invading pneumococci. We also show that our model can be used to study the efficacy of antimicrobials against pneumococci in vivo. Collectively, our data confirm that larval zebrafish can be used to dissect killing mechanisms during pneumococcal infection in vivo and highlight key roles for phagosomal acidification in macrophages for pathogen clearance.
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Greenwood, Brian. "The epidemiology of pneumococcal infection in children in the developing world." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 354, no. 1384 (April 29, 1999): 777–85. http://dx.doi.org/10.1098/rstb.1999.0430.
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Pneumonia causes about three million deaths a year in young children, nearly all of which are in developing countries. Streptococcus pneumoniae (the pneumococcus) is the most important bacterial cause of pneumonia in young children and so is likely to be responsible for a high proportion of these deaths. The pneumococcus is also responsible for a substantial proportion of the 100 000–500 000 deaths that occur from meningitis in children each year. The incidence of invasive pneumococcal disease in children in the developing world is several times higher than in industrialized countries. This discrepancy may, in part, be due to socio–economic differences but genetic factors may also play a role. Children with sickle cell disease have a substantially increased risk of invasive pneumococcal infection and a search is being made for other possible genetic risk factors. Infection with human immunodeficiency virus (HIV) also predisposes to invasive pneumococcal disease and so the incidence of this disease in young children is expected to rise as increasing numbers of African and Asian children are born with a perinatally acquired HIV infection. Until recently, pneumococcal infections could be treated effectively with penicillin, a cheap and safe antibiotic. However, pneumococci that are resistant to penicillin are becoming prevalent in many countries, necessitating a change to more costly antibiotics which may be beyond the reach of the health services of poor, developing counties. The spread of antibiotic resistance has provided an added stimulus to the development of vaccines that might be able to prevent pneumococcal disease in infants. Recently developed polysaccharide–protein conjugate vaccines show promise and are now undergoing field trials. How deployment of these vaccines will influence the balance between invasive pneumococcal infections and asymptomatic nasopharyngeal carriage of pneumococci is uncertain.
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Rada, Balazs, Aaron Gingerich, Fayhaa Doja, Rachel Thomason, Eszter Toth, Jessica L. Bradshaw, and Larry S. McDaniel. "Lactoperoxidase-generated hypothiocyanite efficiently kills Streptococcus pneumoniae." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 227.17. http://dx.doi.org/10.4049/jimmunol.204.supp.227.17.
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Abstract Streptococcus pneumoniae (pneumococcus) infections affect millions of people worldwide, cause serious mortality and represent a major economic burden. Airway epithelial cells, the primary responders to pneumococcal infection, orchestrate an extracellular antimicrobial system consisting of lactoperoxidase, thiocyanate anion and hydrogen peroxide (H2O2). Lactoperoxidase oxidizes thiocyanate using H2O2 into the final product hypothiocyanite. While hypothiocyanite has known antimicrobial effects against a wide range of microorganisms, its effect on pneumococcus has never been studied. To test this, pneumococci were exposed to hypothiocyanite generated enzymatically in a cell-free in vitro system. Bacterial killing was determined by colony forming units on agar plates while bacteriostatic effects were measured by changes in optical density of liquid cultures. We demonstrate hypothiocyanite exerted robust killing of several pneumococcal strains. Nonencapsulated pneumococcal mutants were killed to the same extent as their parental strains, indicating no role of the capsule in protection against hypothiocyanite. Catalase, an H2O2 scavenger, inhibited pneumococcal killing by hypothiocyanite under all circumstances. Interestingly, a pneumococcal mutant deficient in pyruvate oxidase, the main bacterial H2O2 source, had enhanced susceptibility to hypothiocyanite indicating the role of this gene in partial protection of the bacterium against this oxidizing agent. Overall, numerous pneumococcal strains were found to be susceptible to lactoperoxidase-generated hypothiocyanite in vitro, which presents an opportunity to explore hypothiocyanite as a potential novel anti-pneumococcal therapy.
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PICHON, B., H. V. BENNETT, A. EFSTRATIOU, M. P. E. SLACK, and R. C. GEORGE. "Genetic characteristics of pneumococcal disease in elderly patients before introducing the pneumococcal conjugate vaccine." Epidemiology and Infection 137, no. 7 (January 23, 2009): 1049–56. http://dx.doi.org/10.1017/s0950268808001787.
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SUMMARYStreptococcus pneumoniaestrains causing invasive pneumococcal disease (IPD) in the elderly population of England and Wales during the winter of 2003/2004 (1 November 2003 to 30 April 2004) were characterized by serotyping and genotyping in order to determine their population structure in the elderly. Serotyping and multilocus sequence typing (MLST) were carried out on 542 invasive isolates referred to the Respiratory and Systemic Infection Laboratory. Pneumococci were distributed among 32 serotypes and 144 MLST sequence types. A high genetic diversity was observed within the major serotypes. Genetic relatedness varied with regard to serotype. Isolates within serotypes 3, 7F and 8 were the most genetically related whereas serotypes 6A and 19F comprised isolates originating from unrelated ancestors. There was indirect evidence that some pneumococci were derived from clones that had undergone capsular switching in the past. Interestingly one case of IPD was caused by a pneumococcus originating from a clone that had undergone capsular switching from serotype 18C, a serotype included in 7-valent pneumococcal conjugate vaccine (PCV) to serotype 1 (serotype not included in PCV) suggesting that virulent clones with the potential ability to evade PCV existed in the pneumococcal population prior to the routine introduction of this vaccine. Isolates from 28 cases of apparent 23-valent pneumococcal polysaccharide vaccine (PPV) failure were included but there was no evidence of the emergence of particular clones associated with vaccine failures. Longitudinal studies based on serotypic and genetic characterization of pneumococci are fundamental to understanding the impact of both PPV and PCV on the genetic structure of pneumococcal populations.
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van Tonder, Andries J., James E. Bray, Lucy Roalfe, Rebecca White, Marta Zancolli, Sigríður J. Quirk, Gunnsteinn Haraldsson, et al. "Genomics Reveals the Worldwide Distribution of Multidrug-Resistant Serotype 6E Pneumococci." Journal of Clinical Microbiology 53, no. 7 (May 13, 2015): 2271–85. http://dx.doi.org/10.1128/jcm.00744-15.
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The pneumococcus is a leading pathogen infecting children and adults. Safe, effective vaccines exist, and they work by inducing antibodies to the polysaccharide capsule (unique for each serotype) that surrounds the cell; however, current vaccines are limited by the fact that only a few of the nearly 100 antigenically distinct serotypes are included in the formulations. Within the serotypes, serogroup 6 pneumococci are a frequent cause of serious disease and common colonizers of the nasopharynx in children. Serotype 6E was first reported in 2004 but was thought to be rare; however, we and others have detected serotype 6E among recent pneumococcal collections. Therefore, we analyzed a diverse data set of ∼1,000 serogroup 6 genomes, assessed the prevalence and distribution of serotype 6E, analyzed the genetic diversity among serogroup 6 pneumococci, and investigated whether pneumococcal conjugate vaccine-induced serotype 6A and 6B antibodies mediate the killing of serotype 6E pneumococci. We found that 43% of all genomes were of serotype 6E, and they were recovered worldwide from healthy children and patients of all ages with pneumococcal disease. Four genetic lineages, three of which were multidrug resistant, described ∼90% of the serotype 6E pneumococci. Serological assays demonstrated that vaccine-induced serotype 6B antibodies were able to elicit killing of serotype 6E pneumococci. We also revealed three major genetic clusters of serotype 6A capsular sequences, discovered a new hybrid 6C/6E serotype, and identified 44 examples of serotype switching. Therefore, while vaccines appear to offer protection against serotype 6E, genetic variants may reduce vaccine efficacy in the longer term because of the emergence of serotypes that can evade vaccine-induced immunity.
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Marks, Laura R., G. Iyer Parameswaran, and Anders P. Hakansson. "Pneumococcal Interactions with Epithelial Cells Are Crucial for Optimal Biofilm Formation and ColonizationIn VitroandIn Vivo." Infection and Immunity 80, no. 8 (May 29, 2012): 2744–60. http://dx.doi.org/10.1128/iai.00488-12.
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ABSTRACTThe human nasopharynx is the main reservoir forStreptococcus pneumoniae(the pneumococcus) and the source for both horizontal spread and transition to infection. Some clinical evidence indicates that nasopharyngeal carriage is harder to eradicate with antibiotics than is pneumococcal invasive disease, which may suggest that colonizing pneumococci exist in biofilm communities that are more resistant to antibiotics. While pneumococcal biofilms have been observed during symptomatic infection, their role in colonization and the role of host factors in this process have been less studied. Here, we show for the first time that pneumococci form highly structured biofilm communities during colonization of the murine nasopharynx that display increased antibiotic resistance. Furthermore, pneumococcal biofilms grown on respiratory epithelial cells exhibited phenotypes similar to those observed during colonizationin vivo, whereas abiotic surfaces produced less ordered and more antibiotic-sensitive biofilms. The importance of bacterial-epithelial cell interactions during biofilm formation was shown using both clinical strains with variable colonization efficacies and pneumococcal mutants with impaired colonization characteristicsin vivo. In both cases, the ability of strains to form biofilms on epithelial cells directly correlated with their ability to colonize the nasopharynxin vivo, with colonization-deficient strains forming less structured and more antibiotic-sensitive biofilms on epithelial cells, an association that was lost when grown on abiotic surfaces. Thus, these studies emphasize the importance of host-bacterial interactions in pneumococcal biofilm formation and provide the first experimental data to explain the high resistance of pneumococcal colonization to eradication by antibiotics.
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Francois Watkins, Louise K., Jennifer L. Milucky, Lesley McGee,, Florence Siné St.-Surin, Pengbo Liu, Theresa Tran, Sopio Chochua, et al. "Nasopharyngeal Carriage of Streptococcus pneumoniae Among Young Children in Haiti Before Pneumococcal Conjugate Vaccine Introduction." Journal of Infectious Diseases 224, Supplement_3 (September 1, 2021): S248—S257. http://dx.doi.org/10.1093/infdis/jiab119.
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Abstract Background Streptococcus pneumoniae, or pneumococcus, is a leading cause of morbidity and mortality in children worldwide. Pneumococcal conjugate vaccines (PCV) reduce carriage in the nasopharynx, preventing disease. We conducted a pneumococcal carriage study to estimate the prevalence of pneumococcal colonization, identify risk factors for colonization, and describe antimicrobial susceptibility patterns among pneumococci colonizing young children in Port-au-Prince, Haiti, before introduction of 13-valent PCV (PCV13). Methods We conducted a cross-sectional study of children aged 6–24 months at an immunization clinic in Port-au-Prince between September 2015 and January 2016. Consenting parents were interviewed about factors associated with pneumococcal carriage; nasopharyngeal swabs were collected from each child and cultured for pneumococcus after broth enrichment. Pneumococcal isolates were serotyped and underwent antimicrobial susceptibility testing. We compared frequency of demographic, clinical, and environmental factors among pneumococcus-colonized children (carriers) to those who were not colonized (noncarriers) using unadjusted bivariate analysis and multivariate logistic regression. Results Pneumococcus was isolated from 308 of the 685 (45.0%) children enrolled. Overall, 157 isolates (50.8%) were PCV13 vaccine-type serotypes; most common were 6A (13.3%), 19F (12.6%), 6B (9.7%), and 23F (6.1%). Vaccine-type isolates were significantly more likely to be nonsusceptible to ≥1 antimicrobial (63.1% vs 45.4%, P = .002). On bivariate analysis, carriers were significantly more likely than noncarriers to live in a household without electricity or running water, to share a bedroom with ≥3 people, to have a mother or father who did not complete secondary education, and to have respiratory symptoms in the 24 hours before enrollment (P < .05 for all comparisons). On multivariable analysis, completion of the pentavalent vaccination series (targeting diphtheria, pertussis, tetanus, hepatitis B, and Haemophilus influenzae type b) remained significantly more common among noncarriers. Conclusions Nearly a quarter of healthy children surveyed in Haiti were colonized with vaccine-type pneumococcal serotypes. This baseline carriage study will enable estimation of vaccine impact following nationwide introduction of PCV13.
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Srivastava, Amit, Heather Casey, Nathaniel Johnson, Ofer Levy, and Richard Malley. "Recombinant Bactericidal/Permeability-Increasing Protein rBPI21 Protects against Pneumococcal Disease." Infection and Immunity 75, no. 1 (November 13, 2006): 342–49. http://dx.doi.org/10.1128/iai.01089-06.
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ABSTRACT Bactericidal/permeability-increasing (BPI) protein has been shown to play an important role in innate immunity to gram-negative bacteria, by direct microbicidal as well as endotoxin-neutralizing action. Here we examined potential interactions between a recombinant 21-kDa bioactive fragment of BPI, rBPI21, and the gram-positive pathogen Streptococcus pneumoniae. rBPI21 bound to pneumococci and pneumolysin (Ply) in a direct and specific fashion. We observed an enhanced inflammatory response in mouse macrophages when rBPI21 was combined with killed pneumococci or supernatant from overnight growth of pneumococci. In addition, rBPI21 augmented the proapoptotic activity of Ply+ (but not Ply−) pneumococci in TLR4-defective murine macrophages (known to be defective also in their apoptotic response to pneumolysin) in a tumor necrosis factor alpha-dependent manner. rBPI21 also enhanced the association of pneumococci with murine macrophages. In a model of invasive pneumococcal disease in TLR4-defective mice, the intranasal administration of rBPI21 following intranasal inoculation of Ply+ pneumococci both enhanced upper respiratory tract cell apoptosis and prolonged survival. We have thus discovered a novel interaction between pneumococcus and rBPI21, a potent antimicrobial peptide previously considered to target only gram-negative bacteria.
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Klugman, K. P. "Pneumococcal resistance to antibiotics." Clinical Microbiology Reviews 3, no. 2 (April 1990): 171–96. http://dx.doi.org/10.1128/cmr.3.2.171.
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The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin-binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk.
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Szabó, Bálint Gergely, Katalin Szidónia Lénárt, Béla Kádár, Andrea Gombos, Balázs Dezsényi, Judit Szanka, Ilona Bobek, and Gyula Prinz. "A Streptococcus pneumoniae (pneumococcus) -infekciók ezer arca." Orvosi Hetilap 156, no. 44 (November 2015): 1769–77. http://dx.doi.org/10.1556/650.2015.30293.
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Incidence and mortality rates of infections caused by Streptococcus pneumoniae (pneumococcus) are high worldwide and in Hungary among paediatric as well as adult populations. Pneumococci account for 35–40% of community acquired adult pneumonias requiring hospitalization, while 25–30% of Streptococcus pneumoniae pneumonias are accompanied by bacteraemia. 5–7% of all infections are fatal but this rate is exponentially higher in high risk patients and elderly people. Mortality could reach 20% among patients with severe invasive pneumococcal infections. Complications may develop despite administration of adequate antibiotics. The authors summarize the epidemiology of pneumococcal infections, pathogenesis of non-invasive and invasive disease and present basic clinical aspects through demonstration of four cases. Early risk stratification, sampling of hemocultures, administration of antibiotics and wider application of active immunization could reduce the mortality of invasive disease. Anti-pneumococcal vaccination is advisable for adults of ≥50 years and high risk patients of ≥18 years who are susceptible to pneumococcal disease. Orv. Hetil., 2015, 156(44), 1769–1777.
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Dai, V. T. T., J. Beissbarth, P. V. Thanh, P. T. Hoan, H. N. L. Thuy, T. N. Huu, K. Bright, et al. "Hospital surveillance predicts community pneumococcal antibiotic resistance in Vietnam." Journal of Antimicrobial Chemotherapy 75, no. 10 (July 29, 2020): 2902–6. http://dx.doi.org/10.1093/jac/dkaa276.
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Abstract Background In Vietnam, Streptococcus pneumoniae is a leading cause of disease, including meningitis. Antibiotics are available without physician prescription at community pharmacies and rates of antibiotic non-susceptibility are high. Appropriate treatment and antibiotic stewardship need to be informed by surveillance data. Objectives To report community-based pneumococcal antibiotic susceptibility testing data from children enrolled in a pneumococcal conjugate vaccine trial in Ho Chi Minh City [the Vietnam Pneumococcal Project (ViPP)] and compare these with published hospital-based data from the nationwide Survey of Antibiotic Resistance (SOAR) to determine whether hospital surveillance data provide an informative estimate of circulating pneumococcal resistance. Methods Pneumococcal isolates from 234 nasopharyngeal swabs collected from ViPP participants at 12 months of age underwent antibiotic susceptibility testing using CLSI methods and the data were compared with SOAR data. Results Antibiotic susceptibility testing identified penicillin-non-susceptible pneumococci in 93.6% of pneumococcus-positive ViPP swabs (oral, non-meningitis breakpoints). Non-susceptibility to erythromycin, trimethoprim/sulfamethoxazole, clindamycin and tetracycline also exceeded 79%. MDR, defined as non-susceptibility to three or more classes of antibiotic, was common (94.4% of swabs). Low or no resistance was detected for ceftriaxone (non-meningitis breakpoints), ofloxacin and vancomycin. Antibiotic non-susceptibility rates in ViPP and SOAR were similar for several antibiotics tested. Conclusions A very high proportion of pneumococci carried in the community are MDR. Despite wide disparities in population demographics between ViPP and SOAR, the non-susceptibility rates for several antibiotics were comparable. Thus, with some qualification, hospital antibiotic susceptibility testing data in Vietnam can inform circulating pneumococcal antibiotic non-susceptibility in young children, the group at highest risk of pneumococcal disease, to guide antibiotic prescribing and support surveillance strategies.
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Schmeck, Bernd, Ralph Gross, Phillipe Dje N′Guessan, Andreas C. Hocke, Sven Hammerschmidt, Tim J. Mitchell, Simone Rosseau, Norbert Suttorp, and Stefan Hippenstiel. "Streptococcus pneumoniae-Induced Caspase 6-Dependent Apoptosis in Lung Epithelium." Infection and Immunity 72, no. 9 (September 2004): 4940–47. http://dx.doi.org/10.1128/iai.72.9.4940-4947.2004.
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ABSTRACT Streptococcus pneumoniae is the major pathogen of community-acquired pneumonia and one of the most common causes of death due to infectious diseases in industrialized countries. Lung epithelium lines the airways and constitutes the first line of innate defense against respiratory pathogens. Little is known about the molecular interaction of pneumococci with lung epithelial cells. Apoptosis of lung epithelium is involved in some bacterial lung infections. In this study different pneumococcal strains specifically induced either apoptotic or necrotic death of human alveolar and bronchial epithelial cells. Pneumococcus-induced apoptosis did not depend on the virulence factors pneumolysin and H2O2. Apoptotic cells showed increased activity of caspases 6, 8, and 9 but not increased activity of caspase 3. Moreover, programmed cell death could be strongly reduced by a caspase 6 inhibitor and a pan-caspase inhibitor. Inhibitors of calpain and chymotrypsin- and trypsin-like proteases also reduced pneumococcus-induced apoptosis. Furthermore, pneumococcus-infected human alveolar epithelial cells showed Bid cleavage and reduced levels of Bcl2 and Bax. Overexpression of Bcl2 in these cells reduced apoptosis significantly. Thus, pneumococci induced apoptosis of human alveolar and bronchial epithelial cells. Programmed cell death was executed by caspase 6 and noncaspase proteases, but not by caspase 3, and could be blocked by overexpression of Bcl2.
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Somova, A. V., V. V. Romanenko, and A. A. Golubkova. "Epidemiology of S. Pneumoniae-associated Pneumonias and the Analysis of Effectiveness of Vaccination against Pneumococcal Infection in Children under the Age of Six." Epidemiology and Vaccine Prevention 17, no. 1 (February 20, 2018): 25–32. http://dx.doi.org/10.31631/2073-3046-2018-17-1-25-32.
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Pneumococcal infection is one of the main causes of acute respiratory diseases and exacerbation of chronic ones. In order to study the prevalence of community-acquired pneumonia, the etiologic role of S. pneumoniaе and effectiveness of vaccination among children under the age of 6 in the town of industrial cities, we conducted a non-interventional epidemiologic study of serotypes of circulating pneumococci and their compliance with the declared composition of vaccines recommended for prevention of pneumococcal infection in children. We also studied incidence rates of community-acquired pneumonias among children under the age of five vaccinated against pneumococcal infection, depending on the schedule and beginning of immunization. Our findings indicate a significant role of pneumococcus in the etiology of community-acquired pneumonias among children under the age of 17 (24.14%).The established spectrum of serotypes of pneumococcus from nasopharyngial swabs in children under the age of 17 with community-acquired pneumonia in the town of this city showed that such serotypes as 19F, 14, 9V/A, 15A/F, 6A/B/C, 3, and 23F contributed the most to the development of pneumonia (79.97%). Pneumococcus serotypes found corresponded to the composition of PCV13 in 76.36% of cases and to that of PCV10 – in 67.27%. Proven the effectiveness of the vaccine, the rate of epidemiologic effectiveness was 48.7% in relation to pneumonia of any etiology. Shown the largest epidemiological effectiveness (54.8%) of vaccination in children vaccinated in an early period (under the age of 1).
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Mirzaeva, A. R., T. V. Kulichenko, O. I. Lebedeva, Z. A. Alacheva, T. G. Kuznetsova, N. M. Alyabyeva, E. A. Brzhozovskaya, and N. A. Mayanskiy. "NASOPHARYNGEAL CARRIAGE OF STREPTOCOCCUS PNEUMONIAE IN CHILDREN UNDER 5 YEARS OF AGE AFTER INTRODUCTION OF PNEUMOCOCCAL CONJUGATE VACCINATION IN THE REPUBLIC OF KHAKASSIA." Russian Pediatric Journal 22, no. 4 (August 15, 2019): 196–204. http://dx.doi.org/10.18821/1560-9561-2019-22-4-196-204.
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Introduction The dynamic study of the serotype composition and the level of antibiotic resistance of S. pneumoniae in different regions is the most important component of the control of pneumococcal infections (PI). The aim of the study was to analyze the serotype composition of S. pneumoniae isolated from the nasopharynx in children under 5 years of age, as well as to assess the sensitivity of pneumococci to antimicrobials, depending on the vaccination status and previous antibacterial therapy. Materials and methods A multicenter cohort study of nasopharyngeal carriage, serotype diversity and sensitivity to pneumococcal antibiotics were conducted in 13 centers in the Republic of Khakassia. Results 498 nasopharyngeal smears were collected, pneumococcus was isolated in 51.6% of cases. PI vaccination coverage in the cohort was 67.2%. The carriage of pneumococcus did not differ in children depending on their vaccination status (52.3% in vaccinated and 52.2% in unvaccinated). There was revealed a significant decrease in the carrier rate of pneumococcal vaccine serotypes in the cohort of vaccinated children compared with unvaccinated (17.6% vs 34.7%, p <0.05). High resistance of S. pneumoniae to penicillin (38.6%), macrolides (29.7%), trimethoprim/sulfamethoxazole (28.6%) was found. Amoxicillin resistance accounted for 20.8%, and ceftriaxone - 16.6%. Antibiotic-resistant vaccine serotypes were twofold more common. Conclusion The introduction of mass vaccination against PI in the country does not reduce the nasopharyngeal carriage of pneumococcus, but significantly reduces the circulation of vaccine serotypes, including strains resistant to antibiotics.
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Swiatlo, E., J. King, G. S. Nabors, B. Mathews, and D. E. Briles. "PneumococcalSurface Protein A Is Expressed In Vivo, and Antibodies to PspA AreEffective for Therapy in a Murine Model of PneumococcalSepsis." Infection and Immunity 71, no. 12 (December 2003): 7149–53. http://dx.doi.org/10.1128/iai.71.12.7149-7153.2003.
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ABSTRACT Pneumococcal surface protein A (PspA) is an immunogenic protein expressed on the surface of all strains of Streptococcus pneumoniae (pneumococcus) and induces antibodies which protect against invasive infection in mice. Pneumococci used for infectious challenge in protection studies are typically collected from cultures grown in semisynthetic medium in vitro. The purpose of these studies is to confirm that PspA is expressed by pneumococci during growth in vivo at a level sufficient for antibodies to PspA to be protective. Mice were actively immunized with purified PspA or by passive transfer of monoclonal antibody (MAb) and challenged with a capsular type 3 strain in diluted whole blood from bacteremic mice. All were protected against challenge with 10 times the 50% lethal dose (LD50), and mice challenged with 1,000 times the LD50 had increased survival compared with controls. Additionally, nonimmune mice treated with MAbs to PspA or PspA immune serum at 6 and 12 h after infection with 10 times the LD50 also showed increased survival. Northern blot analysis of RNA from pneumococci grown either in vitro or in vivo showed similar levels of PspA mRNA. These results demonstrate that PspA is expressed in vivo in a mouse model and that immunization with PspA induces antibodies to an antigen which is expressed during the course of invasive infection. Immunotherapy with antibodies to PspA may have some utility in treating pneumococcal infections in humans.
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Valente, Carina, Suzanne Dawid, Francisco R. Pinto, Jason Hinds, Alexandra S. Simões, Katherine A. Gould, Luís A. Mendes, Hermínia de Lencastre, and Raquel Sá-Leão. "TheblpLocus of Streptococcus pneumoniae Plays a Limited Role in the Selection of Strains That Can Cocolonize the Human Nasopharynx." Applied and Environmental Microbiology 82, no. 17 (June 17, 2016): 5206–15. http://dx.doi.org/10.1128/aem.01048-16.
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ABSTRACTNasopharyngeal colonization is important forStreptococcus pneumoniaeevolution, providing the opportunity for horizontal gene transfer when multiple strains co-occur. Although colonization with more than one strain of pneumococcus is common, the factors that influence the ability of strains to coexist are not known. A highly variableblp(bacteriocin-like peptide) locus has been identified in all sequenced strains ofS. pneumoniae. This locus controls the regulation and secretion of bacteriocins, small peptides that target other bacteria. In this study, we analyzed a series of cocolonizing isolates to evaluate the impact of theblplocus on human colonization to determine whether competitive phenotypes of bacteriocin secretion restrict cocolonization. We identified a collection of 135 nasopharyngeal samples cocolonized with two or more strains, totaling 285 isolates. Theblplocus of all strains was characterized genetically with regard to pheromone type, bacteriocin/immunity content, and potential for locus functionality. Inhibitory phenotypes of bacteriocin secretion and locus activity were assessed through overlay assays. Isolates from single colonizations (n= 298) were characterized for comparison. Cocolonizing strains had a high diversity ofblpcassettes; approximately one-third displayed an inhibitory phenotypein vitro. Despitein vitroevidence of competition, pneumococci cocolonized the subjects independently ofblppheromone type (P= 0.577), bacteriocin/immunity content,blplocus activity (P= 0.798), and inhibitory phenotype (P= 0.716). In addition, no significant differences were observed when single and cocolonizing strains were compared. Despite clear evidence ofblp-mediated competition in experimental models, the results of our study suggest that theblplocus plays a limited role in restricting pneumococcal cocolonization in humans.IMPORTANCENasopharyngeal colonization withStreptococcus pneumoniae(pneumococcus) is important for pneumococcal evolution, as the nasopharynx represents the major site for horizontal gene transfer when multiple strains co-occur, a phenomenon known as cocolonization. Understanding how pneumococcal strains interact within the competitive environment of the nasopharynx is of chief importance in the context of pneumococcal ecology. In this study, we used an unbiased collection of naturally co-occurring pneumococcal strains and showed that a biological process frequently used by bacteria for competition—bacteriocin production—is not decisive in the coexistence of pneumococci in the host, in contrast to what has been shown in experimental models.
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Murphy, Clare, Donald Inverarity, Claire McGoldrick, Lindsay Mitchell, Pamela Paterson, Louise Thom, and Giles Edwards. "Treated Follicular Lymphoma, Recurrent Invasive Pneumococcal Disease, Nonresponsiveness to Vaccination, and a Unique Pneumococcus." Case Reports in Hematology 2012 (2012): 1–3. http://dx.doi.org/10.1155/2012/386372.
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A nonneutropenic patient with treated low-grade non-Hodgkin’s (Follicular) lymphoma and secondary hypogammaglobulinemia recovered from pneumococcal pneumonia and septicemia (serotype 7F; ST191) subsequent to influenza A H1N1 (2009). Both infections were potentially vaccine preventable. The patient then developed pneumococcal meningitis due to a serotype 35F pneumococcus with a unique Multilocus Sequence Type (ST7004) which was not vaccine preventable. Patient management was influenced by host predisposition to pneumococcal infection, antibiotic intolerance, and poor response to polysaccharide pneumococcal vaccine. Indirect immunofluorescence with anti-human immunoglobulin confirmed a poor or intermediate response to Pneumovax II. Prophylactic erythromycin was initiated, and immunoglobulin transfusions were also commenced as a preventive strategy. ST7004 is a single locus variant of ST1635 which has been associated with the serotype 35F capsule in England. Thespigene in ST7004, which differentiates it from ST1635, is the same as thespigene present in ST191 which could have arisen from the first disease episode suggesting that horizontal gene transfer may have occurred between different populations of pneumococci present within the patient in an attempt to evade vaccination selection pressure.
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Slotved, Hans-Christian, Christina Guttmann, Charlotte Demuth Pedersen, Jasper Neergaard Jacobsen, and Karen Angeliki Krogfelt. "Evaluation of the Specificity of Pneumococcal Polysaccharide Enzyme-Linked Immunosorbent Assay and the Effect of Serum Adsorption Based on Standard Pneumococcal Serogroup- or Serotype-Specific Rabbit Antisera." Clinical and Vaccine Immunology 16, no. 9 (July 8, 2009): 1279–84. http://dx.doi.org/10.1128/cvi.00143-09.
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ABSTRACT Worldwide, Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality, especially in infants and elderly people. Pneumococcal capsular polysaccharides are well characterized, and more than 90 different serotypes have been identified. Serotype-specific antibodies against the capsular polysaccharide are produced during infection. Detection of antibodies against pneumococci by enzyme-linked immunosorbent assay (ELISA) is performed according to WHO guidelines, using antigens provided by ATCC. However, testing the ELISA for specificity is challenging due to the difficulty in obtaining human naïve serum with pneumococcal antibodies as well as human serum with antibodies against a single serotype. The application of well-defined serotype-specific sera produced in animals to evaluate the specificity of the ATCC antigens and the effect of adsorption with cell wall and 22F polysaccharides has not been performed before, to our knowledge. In this study, the specificity of ATCC antigens (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) was tested by using commercial serotype-, serogroup-, and pool-specific pneumococcal rabbit antisera.
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Green, Angharad E., Deborah Howarth, Chrispin Chaguza, Haley Echlin, R. Frèdi Langendonk, Connor Munro, Thomas E. Barton, et al. "Pneumococcal Colonization and Virulence Factors Identified Via Experimental Evolution in Infection Models." Molecular Biology and Evolution 38, no. 6 (January 27, 2021): 2209–26. http://dx.doi.org/10.1093/molbev/msab018.
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Abstract Streptococcus pneumoniae is a commensal of the human nasopharynx and a major cause of respiratory and invasive disease. We examined adaptation and evolution of pneumococcus, within nasopharynx and lungs, in an experimental system where the selective pressures associated with transmission were removed. This was achieved by serial passage of pneumococci, separately, in mouse models of nasopharyngeal carriage or pneumonia. Passaged pneumococci became more effective colonizers of the respiratory tract and we observed several examples of potential parallel evolution. The cell wall-modifying glycosyltransferase LafA was under strong selection during lung passage, whereas the surface expressed pneumococcal vaccine antigen gene pvaA and the glycerol-3-phosphate dehydrogenase gene gpsA were frequent targets of mutation in nasopharynx-passaged pneumococci. These mutations were not identified in pneumococci that were separately evolved by serial passage on laboratory agar. We focused on gpsA, in which the same single nucleotide polymorphism arose in two independently evolved nasopharynx-passaged lineages. We describe a new role for this gene in nasopharyngeal carriage and show that the identified single nucleotide change confers resistance to oxidative stress and enhanced nasopharyngeal colonization potential. We demonstrate that polymorphisms in gpsA arise and are retained during human colonization. These findings highlight how within-host environmental conditions can determine trajectories of bacterial evolution. Relative invasiveness or attack rate of pneumococcal lineages may be defined by genes that make niche-specific contributions to bacterial fitness. Experimental evolution in animal infection models is a powerful tool to investigate the relative roles played by pathogen virulence and colonization factors within different host niches.
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Seid, Mohammed, Getnet Beyene, Yared Alemu, Bereket Workalemahu, Mulugeta Delbo, Dagimawie Taddesse, Gelila Biresaw, and Aseer Manilal. "Does cotrimoxazole prophylaxis in HIV patients increase the drug resistance of pneumococci? A comparative cross-sectional study in southern Ethiopia." PLOS ONE 15, no. 12 (December 7, 2020): e0243054. http://dx.doi.org/10.1371/journal.pone.0243054.
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Background Infections caused by antibiotic-resistant bacteria results in high rates of morbidity and mortality. Although the prolonged cotrimoxazole (CTX) prophylaxis is arguably associated with the risk of increasing drug resistance in the common pathogens, information regarding its impact on Streptococci pneumoniae / pneumococcus is very limited. Objective This study was conducted to investigate the effect of cotrimoxazole prophylaxis on nasopharyngeal colonization rate and antimicrobial resistance using Streptococci pneumoniae (pneumococcus) as an indicator organism among HIV patients in Arba Minch, Ethiopia. Materials and methods A comparative cross-sectional study was designed and conducted among HIV patients attending the Anti-Retroviral Treatment (ART) clinic of Arba Minch General Hospital (AMGH) from April 01 to August 31, 2018. A total of 252 participants were systematically selected and clustered into two study groups based on their CTX prophylaxis status, one taking CTX prophylaxis, and the second one, the control group (without prophylaxis). A structured questionnaire was used to collect socio-demographic and clinical data from patients. A nasopharyngeal swab was collected and cultured for pneumococcal isolation and identification in accordance with standard microbiological techniques. An antibiotics sensitivity test was performed according to the CLSI guidelines. Data were analyzed using the Statistical package for social science (SPSS) version 20. The primary outcome was determined using logistic regression analysis. Results Of the 252 enrolled HIV patients (mean age (37.38± 9.03 years), 144 (57.14%) were males. The overall, nasopharyngeal colonization rate of S. pneumoniae was 13.5% (95% CI: 8.4–15.6). Asymptomatic pneumococcal carriage rates among patients on CTX prophylaxis and the control group were 16.3%, and 10.3% respectively (p-value = 0.03). Regarding the risk factors analyzed, CTX prophylaxis (AOR: 2.2; 95% CI: 1.05–4.9) and gender (AOR: 2.5; 95% CI: 1.09–5.93) were significantly associated with pneumococcal colonization, showing a male preponderance. Cotrimoxazole-resistant pneumococci were 85.7% vs. 47.4% in the prophylaxis group and the control group respectively and it was statistically significant (AOR: 6.7; 95% CI: 1.3–36). Percentages of multi-drug resistant isolates in these two groups were 38.09 and 15.38 respectively (p-value = 0.04). Among the CTX resistant pneumococci isolates, 85% were also found to be co-resistant towards penicillin and was statistically significant. Conclusion The percentage prevalence of nasopharyngeal pneumococci colonization was higher in patients taking CTX prophylaxis. It was noted that CTX prophylaxis eventually results in the selection of cotrimoxazole resistance and multi-drug resistance in pneumococci. There is evidence of existing cross-resistance between cotrimoxazole and penicillin antibiotics. Therefore, CTX prophylaxis must be administered judiciously. Surveillance for antimicrobial susceptibility is warranted where the prophylaxis is common.
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Herring, Sydney E., Sovathiro Mao, Manmeet Bhalla, Essi Y. I. Tchalla, Jill M. Kramer, and Elsa N. Bou Ghanem. "Mitochondrial ROS production by neutrophils is required for host antimicrobial function against Streptococcus pneumoniae and is controlled by A2B adenosine receptor signaling." PLOS Pathogens 18, no. 11 (November 14, 2022): e1010700. http://dx.doi.org/10.1371/journal.ppat.1010700.
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Polymorphonuclear cells (PMNs) control Streptococcus pneumoniae (pneumococcus) infection through various antimicrobial activities. We previously found that reactive oxygen species (ROS) were required for optimal antibacterial function, however, the NADPH oxidase is known to be dispensable for the ability of PMNs to kill pneumococci. In this study, we explored the role of ROS produced by the mitochondria in PMN antimicrobial defense against pneumococci. We found that the mitochondria are an important source of overall intracellular ROS produced by murine PMNs in response to infection. We investigated the host and bacterial factors involved and found that mitochondrial ROS (MitROS) are produced independent of bacterial capsule or pneumolysin but presence of live bacteria that are in direct contact with PMNs enhanced the response. We further found that MyD88-/- PMNs produced less MitROS in response to pneumococcal infection suggesting that released bacterial products acting as TLR ligands are sufficient for inducing MitROS production in PMNs. To test the role of MitROS in PMN function, we used an opsonophagocytic killing assay and found that MitROS were required for the ability of PMNs to kill pneumococci. We then investigated the role of MitROS in host resistance and found that MitROS are produced by PMNs in response to pneumococcal infection. Importantly, treatment of mice with a MitROS scavenger prior to systemic challenge resulted in reduced survival of infected hosts. In exploring host pathways that control MitROS, we focused on extracellular adenosine, which is known to control PMN anti-pneumococcal activity, and found that signaling through the A2B adenosine receptor inhibits MitROS production by PMNs. A2BR-/- mice produced more MitROS and were significantly more resistant to infection. Finally, we verified the clinical relevance of our findings using human PMNs. In summary, we identified a novel pathway that controls MitROS production by PMNs, shaping host resistance against S. pneumoniae.
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Keller, L. E., C. V. Jones, J. A. Thornton, M. E. Sanders, E. Swiatlo, M. H. Nahm, I. H. Park, and L. S. McDaniel. "PspK of Streptococcus pneumoniae Increases Adherence to Epithelial Cells and Enhances Nasopharyngeal Colonization." Infection and Immunity 81, no. 1 (October 31, 2012): 173–81. http://dx.doi.org/10.1128/iai.00755-12.
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Streptococcus pneumoniae(the pneumococcus) colonizes the human nasopharynx and can cause invasive disease aided by the pneumococcal capsule. Group II nontypeableS. pneumoniae(NTSp) lacks a polysaccharide capsule, and a subgroup of NTSp carriage isolates has been found to have a novel gene, pneumococcal surface protein K (pspK), which replaces the capsule locus. A recent rise in the number of NTSp isolates colonizing the human nasopharynx has been observed, but the colonization factors of NTSp have not been well studied. PspK has been shown to play a role in mouse colonization. We therefore examined PspK-mediated immune evasion along with adherence to host cells and colonization. PspK bound human secretory immunoglobulin A (sIgA) but not the complement regulator factor H and did not decrease C3b deposition on the pneumococcal surface. PspK increased binding of pneumococci to epithelial cells and enhanced pneumococcal colonization independently of the genetic background. Understanding how NTSp colonizes and survives within the nasopharynx is important due to the increase in NTSp carriage. Our data suggest that PspK may aid in the persistence of NTSp within the nasopharynx but is not involved in invasion.
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Mills, Richael O., Mohammed R. Abdullah, Samuel A. Akwetey, Dorcas C. Sappor, Gustavo Gámez, and Sven Hammerschmidt. "Molecular Epidemiology of Multidrug-Resistant Pneumococci among Ghanaian Children under Five Years Post PCV13 Using MLST." Microorganisms 10, no. 2 (February 19, 2022): 469. http://dx.doi.org/10.3390/microorganisms10020469.
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Antibiotic resistance in pneumococci contributes to the high pneumococcal deaths in children. We assessed the molecular characteristics of multidrug-resistant (MDR) pneumococci isolated from healthy vaccinated children under five years of age in Cape Coast, Ghana. A total of 43 MDR isolates were selected from 151 pneumococcal strains obtained from nasopharyngeal carriage. All isolates were previously serotyped by multiplex PCR and Quellung reaction. Susceptibility testing was performed using either the E-test or disk diffusion method. Virulence and antibiotic resistance genes were identified by PCR. Molecular epidemiology was analyzed using multilocus sequence typing (MLST). Vaccine-serotypes 23F and 19F were predominant. The lytA and pavB virulence genes were present in all isolates, whiles 14–86% of the isolates carried pilus-islets 1 and 2, pcpA, and psrP genes. Penicillin, tetracycline, and cotrimoxazole resistance were evident in >90% of the isolates. The ermB, mefA, and tetM genes were detected in (n = 7, 16.3%), (n = 4, 9.3%) and (n = 43, 100%) of the isolates, respectively. However, >60% showed alteration in the pbp2b gene. MLST revealed five novel and six known sequence types (STs). ST156 (Spain9V-3) and ST802 were identified as international antibiotic-resistant clones. The emergence of international-MDR clones in Ghana requires continuous monitoring of the pneumococcus through a robust surveillance system.
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Morley, Sharon Celeste, Elizabeth Todd, Lauren Deady, Chris Davis, and Jared Muenzer. "Fatal pneumococcal infection in mice deficient for the actin-bundling protein L-plastin (117.26)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 117.26. http://dx.doi.org/10.4049/jimmunol.188.supp.117.26.
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Abstract L-plastin (LPL) is a leukocyte-specific actin-bundling protein that increases the stability of actin-based structures such as podosomes. Fewer lymphocytes and dendritic cells populate the lungs of LPL-/- mice, presumably due to defective motility of these cell types. To determine whether defective immunity in LPL-/- mice would result in increased susceptibility to infection, we challenged mice intra-tracheally with S. pneumoniae. Less than 20% of LPL-/- mice survived pneumococcal infection, compared to 80% of wild-type mice. Rapid mortality of LPL-/- mice correlated with a 100-fold higher bacterial burden in the blood and bronchoalveolar lavage fluid 24 hours following infection, indicating a significant failure to control and limit bacterial growth in vivo. Defective clearance of pneumococcus was apparent as early as six hours after intra-tracheal challenge, and comparison to Rag1-/- mice indicated defective innate immunity. Preliminary experiments demonstrated defective phagocytosis of pneumococci by LPL-/- alveolar macrophages, providing an explanation for the early clearance defect observed. No requirement for LPL in macrophage function has been previously reported. Delineation of the molecular pathways critical to early innate pulmonary defense against pneumococci through the use of mice deficient for LPL will support research efforts aimed at reducing the global health burden of pneumococcal pneumonia.
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Kurola, Paula, Terhi Tapiainen, Tarja Kaijalainen, Matti Uhari, and Annika Saukkoriipi. "Xylitol and capsular gene expression in Streptococcus pneumoniae." Journal of Medical Microbiology 58, no. 11 (November 1, 2009): 1470–73. http://dx.doi.org/10.1099/jmm.0.011700-0.
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Xylitol is a sugar alcohol that inhibits the growth and adherence of Streptococcus pneumoniae. In clinical trials, xylitol has been shown to decrease the occurrence of acute otitis media in day-care children but did not decrease nasopharyngeal carriage of the pneumococci. It has also been shown that xylitol affects the ultrastructure of the pneumococcal capsule. Here, it was hypothesized that xylitol might affect the expression of pneumococcal capsular genes. Capsule gene expression levels were studied in 24 clinical pneumococcal isolates and one ATCC strain (49619) by using a real-time RT-PCR method targeting the mRNA of the second gene of the pneumococcal capsular locus, the cpsB gene. The isolates were exposed to 5 % glucose, 5 % xylitol and control medium (brain heart infusion medium containing 10 % fetal bovine serum) for 2 h. cpsB gene expression levels were measured by using a relative quantification method with calibrator normalization where the 16S rRNA gene of pneumococcus was used as a reference. Exposure to xylitol lowered cpsB gene expression levels significantly compared with those in the control (P=0.035) and glucose (P=0.011) media. This finding supports previous results where exposure to xylitol changed the ultrastructure of the pneumococcal capsule and could explain further the high clinical efficacy of xylitol in preventing otitis media.
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Li, Yuan, Daniel M. Weinberger, Claudette M. Thompson, Krzysztof Trzciński, and Marc Lipsitch. "Surface Charge of Streptococcus pneumoniae Predicts Serotype Distribution." Infection and Immunity 81, no. 12 (September 30, 2013): 4519–24. http://dx.doi.org/10.1128/iai.00724-13.
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ABSTRACTStreptococcus pneumoniae(pneumococcus) frequently colonizes the human nasopharynx and is an important cause of pneumonia, meningitis, sinusitis, and otitis media. The outer cell surface of pneumococcus may assume various degrees of negative charge depending on the polysaccharide capsule, of which more than 90 serotypes have been identified. The negative charge of capsular polysaccharides has been proposed to electrostatically repel pneumococci from phagocytic cells, and avoidance of phagocytosis correlates with higher carriage prevalence. We hypothesized that the surface charge of pneumococcus contributes to its success in nasopharyngeal carriage by modulating resistance to phagocyte-mediated killing. Here, we measured the surface charge (zeta potential) of laboratory-constructed strains that share a genetic background but differ in serotype and of clinical strains that differ in serotype and genetic background. A more negative surface charge correlated with higher resistance to nonopsonic killing by human neutrophilsin vitro. In addition, a more negative zeta potential was associated with higher carriage prevalence in human populations before and after the widespread use of the pneumococcal conjugate vaccine PCV7. We also confirmed that capsule is the major determinant of net surface charge in clinical isolates with diverse backgrounds. We noted that exceptions exist to the idea that a higher magnitude of negative charge predicts higher prevalence. The results indicated that zeta potential is strongly influenced by pneumococcal capsule type but is unlikely to be the only important mechanism by which capsule interacts with host.
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Tchalla, Essi Y. I., Manmeet Bhalla, Elizabeth A. Wohlfert, and Elsa N. Bou Ghanem. "Neutrophils Are Required During Immunization With the Pneumococcal Conjugate Vaccine for Protective Antibody Responses and Host Defense Against Infection." Journal of Infectious Diseases 222, no. 8 (May 11, 2020): 1363–70. http://dx.doi.org/10.1093/infdis/jiaa242.
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Abstract Neutrophils can shape adaptive immunity; however, their role in vaccine-induced protection against infections in vivo remains unclear. Here, we tested their role in the clinically relevant polysaccharide conjugate vaccine against Streptococcus pneumoniae (pneumococcus). We antibody depleted neutrophils during vaccination, allowed them to recover, and 4 weeks later challenged mice with pneumococci. We found that while isotype-treated vaccinated controls were protected against an otherwise lethal infection in naive mice, full protection was lost upon neutrophil depletion. Compared to vaccinated controls, neutrophil-depleted mice had higher lung bacterial burdens, increased incidence of bacteremia, and lower survival rates. Sera from neutrophil-depleted mice had less antipneumococcal IgG2c and IgG3, were less efficient at inducing opsonophagocytic killing of bacteria by neutrophils in vitro, and were worse at protecting naive mice against pneumococcal pneumonia. In summary, neutrophils are required during vaccination for optimal host protection, which has important implications for future vaccine design against pneumococci and other pathogens.
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SEMENOV, S. A., and G. R. KHASANOVA. "Risk factors for development of Streptococcus pneumoniae resistance to antibiotics." Practical medicine 18, no. 6 (2020): 113–18. http://dx.doi.org/10.32000/2072-1757-2020-6-113-118.
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Streptococcus pneumoniae is responsible for a wide range of human diseases, often with a severe course and prognosis. The growing resistance of pneumococci to certain classes of antibiotics limits the treatment of pneumococcal infections. The study of factors that influence the formation of antibiotic resistance of the pathogen is important for developing a strategy to counter this phenomenon and for predicting the presence of microbial resistance in a particular patient when choosing a drug for empirical therapy. This review presents the results of studies of some potential risk factors for the formation of Streptococcus pneumoniae resistance to antibiotics. The most important of these is the previous administration of antibiotics, especially in the last few months. Previous diseases, previous hospitalization, and the nosocomial nature of pneumonia are also considered as factors that allow predicting the colonization of loci by antibiotic-resistant strains of pneumococci. Staying at long-term care facilities and attending organized groups (schools and kindergartens) may also increase the risk of colonization of the respiratory tract by antibiotic-resistant strains of pneumococci. The frequency of isolation of pneumococcus strains insensitive to certain antibiotics is also characterized by wide geographical variability.
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Terra, Vanessa S., Karen A. Homer, Susmitha G. Rao, Peter W. Andrew, and Hasan Yesilkaya. "Characterization of Novel β-Galactosidase Activity That Contributes to Glycoprotein Degradation and Virulence in Streptococcus pneumoniae." Infection and Immunity 78, no. 1 (October 19, 2009): 348–57. http://dx.doi.org/10.1128/iai.00721-09.
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ABSTRACT The pneumococcus obtains its energy from the metabolism of host glycosides. Therefore, efficient degradation of host glycoproteins is integral to pneumococcal virulence. In search of novel pneumococcal glycosidases, we characterized the Streptococcus pneumoniae strain D39 protein encoded by SPD_0065 and found that this gene encodes a β-galactosidase. The SPD_0065 recombinant protein released galactose from desialylated fetuin, which was used here as a model of glycoproteins found in vivo. A pneumococcal mutant with a mutation in SPD_0065 showed diminished β-galactosidase activity, exhibited an extended lag period in mucin-containing defined medium, and cleaved significantly less galactose than the parental strain during growth on mucin. As pneumococcal β-galactosidase activity had been previously attributed solely to SPD_0562 (bgaA), we evaluated the contribution of SPD_0065 and SPD_0562 to total β-galactosidase activity. Mutation of either gene significantly reduced enzymatic activity, but β-galactosidase activity in the double mutant, although significantly less than that in either of the single mutants, was not completely abolished. The expression of SPD_0065 in S. pneumoniae grown in mucin-containing medium or tissues harvested from infected animals was significantly upregulated compared to that in pneumococci from glucose-containing medium. The SPD_0065 mutant strain was found to be attenuated in virulence in a manner specific to the host tissue.
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Gladstone, R. A., J. M. Jefferies, S. N. Faust, and S. C. Clarke. "Continued control of pneumococcal disease in the UK – the impact of vaccination." Journal of Medical Microbiology 60, no. 1 (January 1, 2011): 1–8. http://dx.doi.org/10.1099/jmm.0.020016-0.
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Streptococcus pneumoniae, also known as the pneumococcus, is an important cause of morbidity and mortality in the developed and developing world. Pneumococcal conjugate vaccines were first introduced for routine use in the USA in 2000, although the seven-valent pneumococcal conjugate vaccine (PCV7) was not introduced into the UK's routine childhood immunization programme until September 2006. After its introduction, a marked decrease in the incidence of pneumococcal disease was observed, both in the vaccinated and unvaccinated UK populations. However, pneumococci are highly diverse and serotype prevalence is dynamic. Conversely, PCV7 targets only a limited number of capsular types, which appears to confer a limited lifespan to the observed beneficial effects. Shifts in serotype distribution have been detected for both non-invasive and invasive disease reported since PCV7 introduction, both in the UK and elsewhere. The pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix; GlaxoSmithKline) and 13-valent pneumococcal conjugate vaccine (PCV13, Prevenar 13; Pfizer) have been newly licensed. The potential coverage of the 10- and 13-valent conjugate vaccines has also altered alongside serotype shifts. Nonetheless, the mechanism of how PCV7 has influenced serotype shift is not clear-cut as the epidemiology of serotype prevalence is complex. Other factors also influence prevalence and incidence of pneumococcal carriage and disease, such as pneumococcal diversity, levels of antibiotic use and the presence of risk groups. Continued surveillance and identification of factors influencing serotype distribution are essential to allow rational vaccine design, implementation and continued effective control of pneumococcal disease.
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Shah, Pratik, Bindu Nanduri, Edwin Swiatlo, Yinfa Ma, and Ken Pendarvis. "Polyamine biosynthesis and transport mechanisms are crucial for fitness and pathogenesis of Streptococcus pneumoniae." Microbiology 157, no. 2 (February 1, 2011): 504–15. http://dx.doi.org/10.1099/mic.0.042564-0.
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Polyamines such as cadaverine, putrescine and spermidine are polycationic molecules that have pleiotropic effects on cells via their interaction with nucleic acids. Streptococcus pneumoniae (the pneumococcus) is a Gram-positive pathogen capable of causing pneumonia, septicaemia, otitis media and meningitis. Pneumococci have a polyamine transport operon (potABCD) responsible for the binding and transport of putrescine and spermidine, and can synthesize cadaverine and spermidine using their lysine decarboxylase (cad) and spermidine synthase (speE) enzymes. Previous studies from our laboratory have shown that an increase in PotD expression is seen following exposure to various stresses, while during infection, potD inactivation significantly attenuates pneumococcal virulence, and anti-PotD immune responses are protective in mice. In spite of their relative importance, not much is known about the global contribution of polyamine biosynthesis and transport pathways to pneumococcal disease. Mutants deficient in polyamine biosynthesis (ΔspeE or Δcad) or transport genes (ΔpotABCD) were constructed and were found to be attenuated in murine models of pneumococcal colonization and pneumonia, either alone or in competition with the wild-type strain. The ΔspeE mutant was also attenuated during invasive disease, while the potABCD and cad genes seemed to be dispensable. HPLC analyses showed reduced intracellular polyamine levels in all mutant strains compared with wild-type bacteria. High-throughput proteomic analyses indicated reduced expression of growth, replication and virulence factors in mutant strains. Thus, polyamine biosynthesis and transport mechanisms are intricately linked to the fitness, survival and pathogenesis of the pneumococcus in host microenvironments, and may represent important targets for prophylactic and therapeutic interventions.
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van Rossum, Annemarie M. C., Elena S. Lysenko, and Jeffrey N. Weiser. "Host and Bacterial Factors Contributing to the Clearance of Colonization by Streptococcus pneumoniae in a Murine Model." Infection and Immunity 73, no. 11 (November 2005): 7718–26. http://dx.doi.org/10.1128/iai.73.11.7718-7726.2005.
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ABSTRACT Nasopharyngeal colonization is the first step in the interaction between Streptococcus pneumoniae (the pneumococcus) and its human host. Factors that contribute to clearance of colonization are likely to affect the spread of the pneumococcus and the rate of pneumococcal disease in the population. To identify host and bacterial factors contributing to this process, we examined the time course of colonization using genetically modified mice and pneumococci. Severe combined immunodeficient mice remained persistently colonized (>6 weeks). Major histocompatibility complex II-deficient mice, but not μMT mice, were unable to clear colonization and showed a diminished T helper 1 response. Thus, CD4+ T cells, rather than the generation of specific antibody, appear to be required for effective Th1-mediated clearance. In addition, the microbial pattern recognition receptor toll-like receptor 2 (TLR2), but not TLR4, was necessary for efficient clearance of colonization. In contrast, no role of complement component 3, inducible nitric oxide synthetase, interleukin 12 (IL-12), or IL-4 could be demonstrated. Expression of the pneumococcal toxin pneumolysin enhanced acute localized inflammatory responses and promoted clearance of colonization in a TLR4-independent manner. We conclude that both innate and CD4+ T-cell-mediated immunity and proinflammatory bacterial factors, rather than a humoral adaptive immune response, are important for clearance of S. pneumoniae from the murine nasopharynx.
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Kulohoma, Benard W., Katherine Gray, Arox Kamng'ona, Jennifer Cornick, Stephen D. Bentley, Robert S. Heyderman, and Dean B. Everett. "Piliation of Invasive Streptococcus pneumoniae Isolates in the Era before Pneumococcal Conjugate Vaccine Introduction in Malawi." Clinical and Vaccine Immunology 20, no. 11 (September 11, 2013): 1729–35. http://dx.doi.org/10.1128/cvi.00403-13.
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ABSTRACTThe pneumococcal pilus has been shown to be an important determinant of adhesion and virulence in mouse models of colonization, pneumonia, and bacteremia. A pilus is capable of inducing protective immunity, supporting its inclusion in next-generation pneumococcal protein vaccine formulations. Whether this vaccine target is common among pneumococci in sub-Saharan Africa is uncertain. To define the prevalence and genetic diversity of type I and II pili among invasive pneumococci in Malawi prior to the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into routine childhood immunization, we examined 188Streptococcus pneumoniaeisolates collected between 2002 and 2008 (17% serotype 1). In this region of high disease burden, we found a low frequency of invasive piliated pneumococci (14%) and pilus gene sequence diversity similar to that seen previously in multiple global pneumococcal lineages. All common serotypes with pilus were covered by PCV13 and so we predict that pilus prevalence will be reduced in the Malawian pneumococcal population after PCV13 introduction.
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Moscoso, Miriam, Ernesto García, and Rubens López. "Biofilm Formation by Streptococcus pneumoniae: Role of Choline, Extracellular DNA, and Capsular Polysaccharide in Microbial Accretion." Journal of Bacteriology 188, no. 22 (August 25, 2006): 7785–95. http://dx.doi.org/10.1128/jb.00673-06.
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ABSTRACTStreptococcus pneumoniaecolonizes the human upper respiratory tract, and this asymptomatic colonization is known to precede pneumococcal disease. In this report, chemically defined and semisynthetic media were used to identify the initial steps of biofilm formation by pneumococcus during growth on abiotic surfaces such as polystyrene or glass. Unencapsulated pneumococci adhered to abiotic surfaces and formed a three-dimensional structure about 25 μm deep, as observed by confocal laser scanning microscopy and low-temperature scanning electron microscopy. Choline residues of cell wall teichoic acids were found to play a fundamental role in pneumococcal biofilm development. The role in biofilm formation of choline-binding proteins, which anchor to the teichoic acids of the cell envelope, was determined using unambiguously characterized mutants. The results showed that LytA amidase, LytC lysozyme, LytB glucosaminidase, CbpA adhesin, PcpA putative adhesin, and PspA (pneumococcal surface protein A) mutants had a decreased capacity to form biofilms, whereas no such reduction was observed in Pce phosphocholinesterase or CbpD putative amidase mutants. Moreover, encapsulated, clinical pneumococcal isolates were impaired in their capacity to form biofilms. In addition, a role for extracellular DNA and proteins in the establishment ofS. pneumoniaebiofilms was demonstrated. Taken together, these observations provide information on conditions that favor the sessile mode of growth byS. pneumoniae. The experimental approach described here should facilitate the study of bacterial genes that are required for biofilm formation. Those results, in turn, may provide insight into strategies to prevent pneumococcal colonization of its human host.
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Pérez-Trallero, Emilio, José M. Marimón, Julián Larruskain, Marta Alonso, and María Ercibengoa. "Antimicrobial Susceptibilities and Serotypes of Streptococcus pneumoniae Isolates from Elderly Patients with Pneumonia and Acute Exacerbation of Chronic Obstructive Pulmonary Disease." Antimicrobial Agents and Chemotherapy 55, no. 6 (March 14, 2011): 2729–34. http://dx.doi.org/10.1128/aac.01546-10.
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ABSTRACTIn the elderly,Streptococcus pneumoniaeis the most common cause of pneumonia and one of the most frequently isolated pathogens in cases of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study was conducted to compare the pneumococcal isolates obtained during episodes of AECOPD and pneumonia in patients of ≥65 years old and to analyze whether in patients with AECOPD and pneumonia within a short interval, the same isolate caused both episodes. This laboratory-based study was performed between 2005 and 2008. Pneumococcal isolates from episodes of pneumonia (n= 401) and AECOPD (n= 398), matched one-to-one by date of isolation, were characterized. The serotypes and genotypes of other pneumococcal isolates causing pneumonia and AECOPD in the same patient were compared. In patients with pneumonia, COPD as an underlying disease was not associated with more-drug-resistant pneumococci. In contrast, isolates causing AECOPD showed higher rates of resistance than those causing pneumonia. Serotypes 1, 3, and 7F were more frequent in pneumonia. The same pneumococcus was involved in 25.7% (9/35 patients) of patients with two consecutive AECOPD episodes but in only 6.3% (2/32 patients) of COPD patients with pneumonia and exacerbation (Fisher's exact test;P= 0.047). Less invasive serotypes were isolated more often in AECOPD and were more resistant to antimicrobials. The presence of a specific pneumococcal serotype in AECOPD does not predict the etiology of subsequent pneumonia.
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Whatmore, Adrian M., Androulla Efstratiou, A. Paul Pickerill, Karen Broughton, Geoffrey Woodard, Daniel Sturgeon, Robert George, and Christopher G. Dowson. "Genetic Relationships between Clinical Isolates of Streptococcus pneumoniae, Streptococcus oralis, and Streptococcus mitis: Characterization of “Atypical” Pneumococci and Organisms Allied to S. mitis HarboringS. pneumoniae Virulence Factor-Encoding Genes." Infection and Immunity 68, no. 3 (March 1, 2000): 1374–82. http://dx.doi.org/10.1128/iai.68.3.1374-1382.2000.
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ABSTRACT The oral streptococcal group (mitis phylogenetic group) currently consists of nine recognized species, although the group has been traditionally difficult to classify, with frequent changes in nomenclature over the years. The pneumococcus (Streptococcus pneumoniae), an important human pathogen, is traditionally distinguished from the most closely related oral streptococcal speciesStreptococcus mitis and Streptococcus oralis on the basis of three differentiating characteristics: optochin susceptibility, bile solubility, and agglutination with antipneumococcal polysaccharide capsule antibodies. However, there are many reports in the literature of pneumococci lacking one or more of these defining characteristics. Sometimes called “atypical” pneumococci, these isolates can be the source of considerable confusion in the clinical laboratory. Little is known to date about the genetic relationships of such organisms with classical S. pneumoniae isolates. Here we describe these relationships based on sequence analysis of housekeeping genes in comparison with previously characterized isolates of S. pneumoniae,S. mitis, and S. oralis. While most pneumococci were found to represent a closely related group these studies identified a subgroup of atypical pneumococcal isolates (bile insoluble and/or “acapsular”) distinct from, though most closely related to, the “typical” pneumococcal isolates. However, a large proportion of isolates, found to be atypical on the basis of capsule reaction alone, did group with typical pneumococci, suggesting that they have either lost capsule production or represent as-yet-unrecognized capsular types. In contrast to typical S. pneumoniae, isolates phenotypically identified as S. mitis and S. oralis, which included isolates previously characterized in taxonomic studies, were genetically diverse. While most of the S. oralis isolates did fall into a well-separated group, S. mitis isolates did not cluster into a well-separated group. During the course of these studies we also identified a number of potentially important pathogenic isolates, which were frequently associated with respiratory disease, that phenotypically and genetically are most closely related to S. mitis but which harbor genes encoding the virulence determinants pneumolysin and autolysin classically associated with S. pneumoniae.
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van Mens, Suzan P., Sabine C. A. Meijvis, Henrik Endeman, Heleen van Velzen-Blad, Douwe H. Biesma, Jan C. Grutters, Bart J. M. Vlaminckx, and Ger T. Rijkers. "Longitudinal Analysis of Pneumococcal Antibodies during Community-Acquired Pneumonia Reveals a Much Higher Involvement of Streptococcus pneumoniae than Estimated by Conventional Methods Alone." Clinical and Vaccine Immunology 18, no. 5 (March 2, 2011): 796–801. http://dx.doi.org/10.1128/cvi.00007-11.
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ABSTRACTIn up to half of all cases of community-acquired pneumonia (CAP), no pathogen can be identified with conventional diagnostic methods. The most common identified causative agent isStreptococcus pneumoniae. In this study, pneumococcal antibody responses during CAP were analyzed to estimate the contribution of the pneumococcus to all cases of CAP for epidemiological purposes. Pneumococcal antibodies against 14 different serotypes were measured in serum of hospitalized CAP patients. Patients participated in one of two consecutive clinical trials in a general 600-bed teaching hospital in the Netherlands (between October 2004 and June 2009). A significant pneumococcal immune response was defined as at least a 2-fold increase in antibody concentrations against a single serotype between an early (day 1) and a late (day 30) serum sample of each patient with an end concentration above 0.35 μg/ml. A total of 349 adult CAP patients participated in two consecutive clinical trials. For 200 patients, sufficient serum samples were available to determine antibody responses: 62 pneumococcal pneumonia patients, 57 nonpneumococcal pneumonia patients, and 81 patients with an unidentified causative agent. A significant immune response was detected in 45% (28/62 patients) of pneumococcal pneumonia patients, in 5% (3/57) of nonpneumococcal pneumonia patients, and in 28% (23/81) of patients with an unidentified causative agent. The estimated contribution of pneumococci in patients with an unidentified causative agent was calculated to be 57% (95% confidence interval, 36 to 86%). A substantial fraction of pneumococcal pneumonia patients do not elicit a serotype-specific immune response.
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Adamou, John E., Theresa M. Wizemann, Philip Barren, and Solomon Langermann. "Adherence of Streptococcus pneumoniae to Human Bronchial Epithelial Cells (BEAS-2B)." Infection and Immunity 66, no. 2 (February 1, 1998): 820–22. http://dx.doi.org/10.1128/iai.66.2.820-822.1998.
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ABSTRACT Pneumococcal adherence to alveolar epithelial cells and nasopharyngeal epithelial cells has been well characterized. However, the interaction of Streptococcus pneumoniae with bronchial epithelial cells has not been studied. We have now shown that pneumococci bind specifically to a human bronchial epithelial cell line (BEAS-2B cells). Pneumococci adhered to BEAS-2B cells in a time- and dose-dependent manner. These results suggest that the bronchial epithelium may serve as an additional site of attachment for pneumococci and demonstrate the utility of the BEAS-2B cell line for studying mechanisms of pneumococcal infection.
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Koroleva, I. S., G. V. Beloshitsky, M. A. Koroleva, and A. A. Mel’Nikova. "Epidemiological Aspects of Pneumococcal Meningitis in the Russian Federation." Epidemiology and Vaccine Prevention 15, no. 5 (October 20, 2016): 6–13. http://dx.doi.org/10.31631/2073-3046-2016-15-5-6-13.
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Introduction. Pneumococcal meningitis (PM) refers to severe manifestations of pneumococcal disease with high mortality and frequent post-infectious complications. In the context of the introduction of vaccination against pneumococcal infections in the Russian Federation healthcare practice increases the importance of close monitoring of the spread of the PM in the country, identifying areas of concern, the definition of risk and serotype structure of pneumococcus, which is an essential component of the assessment of the effectiveness of vaccination. Materials and methods. We collected 1380 cases identified by the PM on the territory of the Russian Federation in 2010 - 2014. We analyzed the incidence, mortality, mortality, age distribution, social belonging PM patients in the whole country, and in the federal districts. Determined serotype affiliation 35 pneumococcal strains isolated from patients with PM in Russia in 2015. Results. The proportion of pneumococci in the etiological structure of bacterial meningitis during the 2010 - 2014 fluctuated in the range of 18.4 - 24.8% and averaged 22.1%. The incidence of the PM in the Russian Federation in 2010 - 2014 determined at the level of 0.19, the death rate - 0.03. The level of mortality in pneumococcal meningitis in the Russian Federation in 2010 - 2014 increased from 13 (2010) to 21.1% (2014), the average was 17.1%. The most vulnerable age groups were adults over 25 years old and children up to 6 years. Among children under the age of 6 years mortality was 10.7%. The study of serotypes of 35 pneumococcal strains showed that in 2015 serotype structure of invasive pneumococcal vaccine serotypes maintained dominance, the proportion reached 75% for PCV13 and 54% for PCV10. Conclusion. The problem of pneumococcal meningitis remains valid in the Russian Federation. Active use of vaccines, especially in children, will reduce the incidence of this infection and the severity of its consequences.
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KORONA-GLOWNIAK, IZABELA, ARTUR NIEDZIELSKI, ANNA MALM, and GRAŻYNA NIEDZIELSKA. "Serotypes and Antibiotic Resistance of Streptococcus pneumoniae from Adenoids in Preschool Children with Recurrent Upper Respiratory Tract Infection." Polish Journal of Microbiology 62, no. 4 (2013): 385–90. http://dx.doi.org/10.33073/pjm-2013-053.
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We investigated children aged 2-5, who had gone adenoidectomy for recurrent and/or persistent symptoms of upper respiratory tract infections for prevalence of pneumococci in adenoid tissue. Serotypes and antibiotic resistance patterns of the isolated pneumococci were determined and also risk factors of pneumococcal colonization were defined. S. pneumoniae colonization in adenoids was found in 62 (60.2%) children. Serotypes belonged to 10-valent and 13-valent pneumococcal conjugated vaccines (PCVs) constituted 56.1% and 68.2% of the isolates, respectively. Decreased susceptibility to penicillin was found in 45.5% of isolates; pneumococci were resistant to cotrimoxazole (62.1%), tetracycline (43.9%), erythromycin (54.5%), clindamycin (54.5%) and chloramphenicol (31.8%). Multidrug resistant S. pneumoniae comprised 57.6% of the isolates. Antibiotic resistant pneumococci were mostly distributed among serotypes belonged to 10-valent and 13-valent PCVs. Good vaccine coverage among the isolated pneumococci confirmed that the introduction of PCVs in the national immunization programme may reduce the pool of resistant and multidrug resistant pneumococci in a community.
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Schrag, Stephanie J., Bernard Beall, and Scott F. Dowell. "Limiting the Spread of Resistant Pneumococci: Biological and Epidemiologic Evidence for the Effectiveness of Alternative Interventions." Clinical Microbiology Reviews 13, no. 4 (October 1, 2000): 588–601. http://dx.doi.org/10.1128/cmr.13.4.588.
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SUMMARY Streptococcus pneumoniae infections are a leading cause of respiratory illness in young children, the elderly, and persons with chronic medical conditions. The emergence of multidrug-resistant pneumococci has compromised the effectiveness of antibiotic therapy for pneumococcal infections. As antibiotic-resistant strains increase in prevalence, there is a need for interventions that minimize the spread of resistant pneumococci. In this review we provide a framework for understanding the spread of pneumococcal resistance and evaluate proposed interventions to reduce this spread. Pneumococci differ from many drug-resistant pathogens because asymptomatic carriers play a key role in transmission of resistant strains and the genes encoding resistance are spread primarily by transformation and conjugative transposons. Evidence suggests that modifications of treatment regimens that have proved effective at limiting resistance in other pathogens may not prevent the spread of pneumococcal resistance. In contrast, programs encouraging more judicious antibiotic use have been shown to be effective. Additionally, a newly developed conjugate pneumococcal vaccine holds great potential as an “antiresistance vaccine” that simultaneously reduces the burden of invasive disease and the prevalence of resistant strains. Several areas of future epidemiologic and laboratory research hold promise to contribute to the reduced spread of pneumococcal resistance.
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Whalan, Rachael H., Simon G. P. Funnell, Lucas D. Bowler, Michael J. Hudson, Andrew Robinson, and Christopher G. Dowson. "Distribution and Genetic Diversity of the ABC Transporter Lipoproteins PiuA and PiaA within Streptococcus pneumoniae and Related Streptococci." Journal of Bacteriology 188, no. 3 (February 1, 2006): 1031–38. http://dx.doi.org/10.1128/jb.188.3.1031-1038.2006.
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ABSTRACT Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. The existence of approximately 90 antigenically distinct capsular serotypes has greatly complicated the development of an effective pneumococcal vaccine. Virulence-associated proteins common and conserved among all capsular types now represent the best strategy to combat pneumococcal infections. PiuA and PiaA are the lipoprotein components of two pneumococcal iron ABC transporters and are required for full virulence in mouse models of infection. Here we describe a study of the distribution and genetic diversity of PiuA and PiaA within typical and atypical S. pneumoniae, Streptococcus oralis, and Streptococcus mitis strains. The genes encoding both PiuA and PiaA were present in all typical pneumococci tested, (covering 20 and 27 serotypes, respectively). The piuA gene was highly conserved within the typical pneumococci (0.3% nucleotide divergence), but was also present in “atypical” pneumococci and the closely related species S. mitis and S. oralis, showing up to 10.4% nucleotide divergence and 7.5% amino acid divergence from the typical pneumococcal alleles. Conversely, the piaA gene was found to be specific to typical pneumococci, 100% conserved, and absent from the oral streptococci, including isolates of S. mitis known to possess pneumolysin and autolysin. These are desirable qualities for a vaccine candidate and as a diagnostic tool for S. pneumoniae.
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Hua, Chun-Zhen, Angela Howard, Richard Malley, and Ying-Jie Lu. "Effect of Nonheme Iron-Containing Ferritin Dpr in the Stress Response and Virulence of Pneumococci." Infection and Immunity 82, no. 9 (July 7, 2014): 3939–47. http://dx.doi.org/10.1128/iai.01829-14.
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ABSTRACTStreptococcus pneumoniae(pneumococcus) produces hydrogen peroxide as a by-product of metabolism and provides a competitive advantage against cocolonizing bacteria. As pneumococci do not produce catalase or an inducible regulator of hydrogen peroxide, the mechanism of resistance to hydrogen peroxide is unclear. A gene responsible for resistance to hydrogen peroxide and iron in other streptococci is that encoding nonheme iron-containing ferritin,dpr, but previous attempts to study this gene in pneumococcus by generating adprmutant were unsuccessful. In the current study, we found thatdpris in an operon with the downstream genesdhfrandclpX. We generated adprdeletion mutant which displayed normal early-log-phase and mid-log-phase growth in bacteriologic medium but survived less well at stationary phase; the addition of catalase partially rescued the growth defect. We showed that thedprmutant is significantly more sensitive to pH, heat, iron concentration, and oxidative stress due to hydrogen peroxide. Using a mouse model of colonization, we also showed that thedprmutant displays a reduced ability to colonize and is more rapidly cleared from the nasopharynx. Our results thus suggest that Dpr is important for pneumococcal resistance to stress and for nasopharyngeal colonization.
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Korona-Glowniak, Izabela, and Anna Malm. "Characteristics ofStreptococcus pneumoniaeStrains Colonizing Upper Respiratory Tract of Healthy Preschool Children in Poland." Scientific World Journal 2012 (2012): 1–10. http://dx.doi.org/10.1100/2012/732901.
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Antibiotic resistant and invasive pneumococci may spread temporally and locally in day care centers (DCCs). We examined 267 children attending four DCCs located in the same city and 70 children staying at home in three seasons (autumn, winter, and spring) to determine prevalence, serotype distribution, antibiotic resistance patterns, and transmission of pneumococcal strains colonizing upper respiratory tract of healthy children without antipneumococcal vaccination. By pheno- and genotyping, we determined clonality of pneumococci, including drug-resistant strains. The average carriage of pneumococci in three seasons was 38.2%. 73.4% and 80.4% of the isolates belonged to serotypes present in 10- and 13-valent conjugate vaccine, respectively. Among the pneumococcal strains, 33.3% were susceptible to all antimicrobial tested and 39.2% had decreased susceptibility to penicillin. Multidrug resistance was common (35.7%); 97.5% of drug-resistant isolates represented serotypes included to 10- and 13-valent conjugate vaccine. According to BOX-PCR, clonality definitely was observed only in case of serotype 14. Multivariate analysis determined DCC attendance as strongly related to pneumococcal colonization in all three seasons, but important seasonal differences were demonstrated. In children attending DCCs, we observed dynamic turnover of pneumococcal strains, especially penicillin nonsusceptible and multidrug resistant, which were mostly distributed among serotypes included to available pneumococcal conjugate vaccines.
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Burns, Tamika, Zhaojing Zhong, Michael Steinitz, and Liise-anne Pirofski. "Modulation of Polymorphonuclear Cell Interleukin-8 Secretion by Human Monoclonal Antibodies to Type 8 Pneumococcal Capsular Polysaccharide." Infection and Immunity 71, no. 12 (December 2003): 6775–83. http://dx.doi.org/10.1128/iai.71.12.6775-6783.2003.
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ABSTRACT Pneumococcal capsular polysaccharide (PS) vaccines induce type-specific immunoglobulin M (IgM), IgG, and IgA. Type-specific IgG to the PS is sufficient to confer protection against the homologous serotype of the pneumococcus, but the efficacies of type-specific IgM and IgA are less well understood. We examined the in vitro activities and efficacies in mice of two human monoclonal antibodies (MAbs) to type 8 PS, NAD (IgA) and D11 (IgM). MAb-mediated opsonophagocytic killing was evaluated after coculture of type 8 pneumococci with human polymorphonuclear cells (PMNs), type-specific or control MAbs, and human complement sources. The effects of the MAbs on PMN interleukin-8 (IL-8) and IL-6 secretion were determined in supernatants from cocultures containing pneumococci and PMNs by enzyme-linked immunosorbent assay. MAb efficacy was determined in an intratracheal model of type 8 infection in mice with classical complement pathway deficiency. Both MAbs were protective in 100% of infected mice. Neither MAb promoted a significant amount of killing of type 8 pneumococci compared to its isotype control MAb. Both type-specific MAbs mediated complement-dependent modulation of PMN IL-8 secretion, with increased secretion at effector/target (E:T) ratios of 500:1 and 50:1 and reduced secretion at 1:5. Trypan blue staining revealed that PMNs cocultured with D11 were less viable at an E:T ratio of 1:5 than PMNs cocultured with the control MAb. PMN IL-6 secretion was increased by both type-specific and control MAbs. These results suggest that certain type-specific IgM and IgAs might contribute to host defense by modulation of the inflammatory response to pneumococci.