Journal articles: 'Nontypeable Haemophilus influenzae'

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Bakaletz, Lauren O., and Laura A. Novotny. "Nontypeable Haemophilus influenzae (NTHi)." Trends in Microbiology 26, no. 8 (August 2018): 727–28. http://dx.doi.org/10.1016/j.tim.2018.05.001.

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Clemans, Daniel L., Carl F. Marrs, Mayuri Patel, Michelle Duncan, and Janet R. Gilsdorf. "Comparative Analysis of Haemophilus influenzae hifA(Pilin) Genes." Infection and Immunity 66, no. 2 (February 1, 1998): 656–63. http://dx.doi.org/10.1128/iai.66.2.656-663.1998.

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ABSTRACT Adherence of Haemophilus influenzae to epithelial cells plays a central role in colonization and is the first step in infection with this organism. Pili, which are large polymorphic surface proteins, have been shown to mediate the binding of H. influenzae to cells of the human respiratory tract. Earlier experiments have demonstrated that the major epitopes of H. influenzae pili are highly conformational and immunologically heterogenous; their subunit pilins are, however, immunologically homogenous. To define the extent of structural variation in pilins, which polymerize to form pili, the pilin genes (hifA) of 26 type a to f and 16 nontypeable strains of H. influenzae were amplified by PCR and subjected to restriction fragment length polymorphism (RFLP) analysis with AluI and RsaI. Six different RFLP patterns were identified. Four further RFLP patterns were identified from published hifA sequences from five nontypeableH. influenzae strains. Two patterns contained only nontypeable isolates; one of these contained H. influenzaebiotype aegyptius strains F3031 and F3037. Another pattern contained predominantly H. influenzae type f strains. All other patterns were displayed by a variety of capsular and noncapsular types. Sequence analysis of selected hifA genes confirmed the 10 RFLP patterns and showed strong identity among representatives displaying the same RFLP patterns. In addition, the immunologic reactivity of pili with antipilus antisera correlated with the groupings of strains based on hifA RFLP patterns. Those strains that show greater reactivity with antiserum directed againstH. influenzae type b strain M43 pili tend to fall into one RFLP pattern (pattern 3); while those strains that show equal or greater reactivity with antiserum directed against H. influenzae type b strain Eagan pili tend to fall in a different RFLP pattern (pattern 1). Sequence analysis of representative HifA pilins from typeable and nontypeable H. influenzaeidentified several highly conserved regions that play a role in bacterial pilus assembly and other regions with considerable amino acid heterogeneity. These regions of HifA amino acid sequence heterogeneity may explain the immunologic diversity seen in intact pili.

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Rubin, L. G., K. Staiman, and N. Kamani. "Occult bacteremia with nontypeable Haemophilus influenzae." Journal of Clinical Microbiology 25, no. 7 (1987): 1314–15. http://dx.doi.org/10.1128/jcm.25.7.1314-1315.1987.

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LaCross, Nathan C., Carl F. Marrs, and Janet R. Gilsdorf. "Population structure in nontypeable Haemophilus influenzae." Infection, Genetics and Evolution 14 (March 2013): 125–36. http://dx.doi.org/10.1016/j.meegid.2012.11.023.

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Foxwell, A. Ruth, Jennelle M. Kyd, and Allan W. Cripps. "Nontypeable Haemophilus influenzae: Pathogenesis and Prevention." Microbiology and Molecular Biology Reviews 62, no. 2 (June 1, 1998): 294–308. http://dx.doi.org/10.1128/mmbr.62.2.294-308.1998.

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SUMMARY In this paper, we describe the ability of nontypeable Haemophilus influenzae (NTHi) to coexist with the human host and the devastating results associated with disruption of the delicate state of balanced pathogenesis, resulting in both acute and chronic respiratory tract infections. It has been seen that the strains of NTHi causing disease show a marked genetic and phenotypic diversity but that changes in the lipooligosaccharide (LOS) and protein size and antigenicity in chronically infected individuals indicate that individual strains of NTHi can remain and adapt themselves to avoid expulsion from their infective niche. The lack of reliance of NTHi on a single mechanism of attachment and its ability to interact with the host with rapid responses to its environment confirmed the success of this organism as both a colonizer and a pathogen. In vitro experiments on cell and organ cultures, combined with otitis media and pulmonary models in chinchillas, rats, and mice, have allowed investigations into individual interactions between NTHi and the mammalian host. The host-organism interaction appears to be a two-way process, with NTHi using cell surface structures to directly interact with the mammalian host and using secreted proteins and LOS to change the mammalian host in order to pave the way for colonization and invasion. Many experiments have also noted that immune system evasion through antigenic variation, secretion of enzymes and epithelial cell invasion allowed NTHi to survive for longer periods despite a specific immune response being mounted to infection. Several outer membrane proteins and LOS derivatives are discussed in relation to their efficacy in preventing pulmonary infections and otitis media in animals. General host responses with respect to age, genetic makeup, and vaccine delivery routes are considered, and a mucosal vaccine strategy is suggested.

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Kubiet, Martin, Reuben Ramphal, Allan Weber, and Arnold Smith. "Pilus-Mediated Adherence of Haemophilus influenzae to Human Respiratory Mucins." Infection and Immunity 68, no. 6 (June 1, 2000): 3362–67. http://dx.doi.org/10.1128/iai.68.6.3362-3367.2000.

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ABSTRACT Haemophilus influenzae, especially the nontypeable strains, are among the most common pathogens encountered in patients with chronic lung disease and otitis media. We and others have demonstrated that respiratory isolates of nontypeable H. influenzae bind to human mucins, but the mechanism of binding is not entirely clear. We have therefore examined the role of pili in the adherence of both type b and nontypeable H. influenzae to human respiratory mucins. We used isogenic H. influenzaestrains with a mutation in the structural gene for pilin (hifA), a laboratory H. influenzae strain transformed with a type b pilus gene cluster (from strain C54), antibodies raised against H. influenzae HifA, andEscherichia coli strains carrying a cloned type b pilus gene cluster (from strain AM30) in these studies. All bacteria lacking HifA or the pilus gene cluster had decreased adherence of piliatedH. influenzae to mucins, and Fab fragments of anti-HifA antibodies inhibited the adherence. E. coli strains carrying the cloned type b pilus gene cluster were six to seven times more adhesive than strains carrying the vector. The role of other putative adhesins was not examined and thus cannot be excluded, but these studies support a role for pili in the binding of H. influenzae to human respiratory mucins.

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Williams, Bryan J., Miriam Golomb, Thomas Phillips, Joshua Brownlee, Maynard V. Olson, and Arnold L. Smith. "Bacteriophage HP2 of Haemophilus influenzae." Journal of Bacteriology 184, no. 24 (December 15, 2002): 6893–905. http://dx.doi.org/10.1128/jb.184.24.6893-6905.2002.

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ABSTRACT Temperate bacteriophages effect chromosomal evolution of their bacterial hosts, mediating rearrangements and the acquisition of novel genes from other taxa. Although the Haemophilus influenzae genome shows evidence of past phage-mediated lateral transfer, the phages presumed responsible have not been identified. To date, six different H. influenzae phages are known; of these, only the HP1/S2 group, which lyosogenizes exclusively Rd strains (which were originally encapsulated serotype d), is well characterized. Phages in this group are genetically very similar, with a highly conserved set of genes. Because the majority of H. influenzae strains are nonencapsulated (nontypeable), it is important to characterize phages infecting this larger, genetically more diverse group of respiratory pathogens. We have identified and sequenced HP2, a bacteriophage of nontypeable H. influenzae. Although related to the fully sequenced HP1 (and even more so to the partially sequenced S2) and similar in genetic organization, HP2 has a few novel genes and differs in host range; HP2 will not infect or lysogenize Rd strains. Genomic comparisons between HP1/S2 and HP2 suggest recent divergence, with new genes completely replacing old ones at certain loci. Sequence comparisons suggest that H. influenzae phages evolve by recombinational exchange of genes with each other, with cryptic prophages, and with the host chromosome.

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Winter, Linda E., and Stephen J. Barenkamp. "HumanAntibodies Specific for the High-Molecular-Weight Adhesion Proteins ofNontypeable Haemophilus influenzae Mediate OpsonophagocyticActivity." Infection and Immunity 71, no. 12 (December 2003): 6884–91. http://dx.doi.org/10.1128/iai.71.12.6884-6891.2003.

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ABSTRACT The HMW1- and HMW2-like adhesion proteins of nontypeable Haemophilus influenzae are expressed by 75% of these strains, and antibodies directed against these proteins are protective in animal models of infection. The purpose of the present study was to define the functional activity of human antibodies specific for these proteins in an in vitro complement-dependent opsonophagocytic assay. Human promyelocytic cell line HL-60 served as the source of phagocytic cells, and a commercial preparation of intravenous immunoglobulin (IVIG) served as the source of human antibodies. High-molecular-weight (HMW) proteins were purified from four prototype nontypeable H. influenzae strains and used to prepare solid-phase affinity columns. IVIG was adsorbed on each column to remove strain-specific anti-HMW antibodies and to allow recovery of affinity-purified anti-HMW antibody fractions. Unadsorbed IVIG killed each of the prototype strains at titers of 1:80 to 1:320. HMW-adsorbed sera demonstrated fourfold decreases in opsonophagocytic titer against the homologous strains compared to unadsorbed IVIG. Affinity-purified anti-HMW antibody preparations demonstrated opsonophagocytic titers of 1:20 to 1:80 against the respective homologous strains and opsonophagocytic titers as high as 1:80 against heterologous strains. None of the affinity-purified anti-HMW antibody preparations was opsonophagocytic for a representative nontypeable H. influenzae strain that did not express HMW1- or HMW2-like proteins. These data demonstrate that human antibodies specific for the HMW1/HMW2-like adhesion proteins of nontypeable H. influenzae are opsonophagocytic and that such antibodies recognize epitopes shared by the HMW proteins of unrelated nontypeable H. influenzae strains. These results argue for continued investigation of the HMW1/HMW2-like proteins as potential vaccine candidates for prevention of disease due to nontypeable H. influenzae.

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SUNAKAWA, Keisuke, Yuriko TAKEUCHI, and Satoshi IWATA. "Nontypeable Haemophilus influenzae （NTHi） Epidemiology." Kansenshogaku Zasshi 85, no. 3 (2011): 227–37. http://dx.doi.org/10.11150/kansenshogakuzasshi.85.227.

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Smith-Vaughan, H. C., K. S. Sriprakash, J. D. Mathews, and D. J. Kemp. "Long PCR-ribotyping of nontypeable Haemophilus influenzae." Journal of clinical microbiology 33, no. 5 (1995): 1192–95. http://dx.doi.org/10.1128/jcm.33.5.1192-1195.1995.

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Poolman, J. T., L. Bakaletz, A. Cripps, P. A. Denoel, A. Forsgren, J. Kyd, and Y. Lobet. "Developing a nontypeable Haemophilus influenzae (NTHi) vaccine." Vaccine 19 (December 2000): S108—S115. http://dx.doi.org/10.1016/s0264-410x(00)00288-7.

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Elango, Danila, and Benjamin L. Schulz. "Phase-Variable Glycosylation in Nontypeable Haemophilus influenzae." Journal of Proteome Research 19, no. 1 (November 27, 2019): 464–76. http://dx.doi.org/10.1021/acs.jproteome.9b00657.

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Cho, Christine, Aroon T. Chande, Lokesh Gakhar, Jason Hunt, Margaret R. Ketterer, and Michael A. Apicella. "Characterization of a nontypeable Haemophilus influenzae thermonuclease." PLOS ONE 13, no. 5 (May 10, 2018): e0197010. http://dx.doi.org/10.1371/journal.pone.0197010.

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Harrison, Alistair, William C. Ray, Beth D. Baker, David W. Armbruster, Lauren O. Bakaletz, and Robert S. Munson. "The OxyR Regulon in Nontypeable Haemophilus influenzae." Journal of Bacteriology 189, no. 3 (December 1, 2006): 1004–12. http://dx.doi.org/10.1128/jb.01040-06.

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ABSTRACT Nontypeable Haemophilus influenzae (NTHi) is a gram-negative bacterium and a common commensal organism of the upper respiratory tract in humans. NTHi causes a number of diseases, including otitis media, sinusitis, conjunctivitis, exacerbations of chronic obstructive pulmonary disease, and bronchitis. During the course of colonization and infection, NTHi must withstand oxidative stress generated by insult due to multiple reactive oxygen species produced endogenously by other copathogens and by host cells. Using an NTHi-specific microarray containing oligonucleotides representing the 1821 open reading frames of the recently sequenced NTHi isolate 86-028NP, we have identified 40 genes in strain 86-028NP that are upregulated after induction of oxidative stress due to hydrogen peroxide. Further comparisons between the parent and an isogenic oxyR mutant identified a subset of 11 genes that were transcriptionally regulated by OxyR, a global regulator of oxidative stress. Interestingly, hydrogen peroxide induced the OxyR-independent upregulation of expression of the genes encoding components of multiple iron utilization systems. This finding suggested that careful balancing of levels of intracellular iron was important for minimizing the effects of oxidative stress during NTHi colonization and infection and that there are additional regulatory pathways involved in iron utilization.

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Baugh, Reginald F., Mark Hatch, and Shan R. Baker. "Nontypeable Haemophilus Influenzae Supraglottitis: Report of Case." Otolaryngology–Head and Neck Surgery 100, no. 6 (June 1989): 617–18. http://dx.doi.org/10.1177/019459988910000618.

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Vitovski, Srdjan, Kim T. Dunkin, Anthony J. Howard, and Jon R. Sayers. "Nontypeable Haemophilus influenzae in Carriage and Disease." JAMA 287, no. 13 (April 3, 2002): 1699. http://dx.doi.org/10.1001/jama.287.13.1699.

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CURRAN, JOHN P. "Nontypeable Haemophilus influenzae Meningitis in an Adolescent." Archives of Pediatrics & Adolescent Medicine 144, no. 5 (May 1, 1990): 517. http://dx.doi.org/10.1001/archpedi.1990.02150290011003.

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Gaultier, Gabrielle N., Kayla N. Colledanchise, Alaa Alhazmi, and Marina Ulanova. "The Immunostimulatory Capacity of Nontypeable Haemophilus influenzae Lipooligosaccharide." Pathogens and Immunity 2, no. 1 (February 16, 2017): 34. http://dx.doi.org/10.20411/pai.v2i1.162.

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Background: We have recently found that lipooligosaccharide (LOS) isolated from encapsulated strains of Haemophilus influenzae (H. influenzae) has strong adjuvant, but diminished pro-inflammatory ability as compared to Escherichia coli lipopolysaccharide (LPS). In this study, we aimed to determine the immunostimulatory capacity of nontypeable/ non-encapsulated H. influenzae (NTHi) LOS by comparing the effect of killed bacteria with LOS isolated from the same strain.Methods: Following stimulation of human monocytic THP-1 cells with killed NTHi strain 375, or with the corresponding amount of LOS, we studied the protein and gene expression of immunostimulatory and antigen-presenting molecules, cytokines, and innate immune receptors.Results: Stimulation with LOS resulted in lower expression of adhesion (CD54, CD58) as well as costimulatory molecules (CD40, CD86), but in higher expression of antigen-presenting molecules (HLA-DR and HLA-ABC) compared to killed NTHi, whereas killed bacteria induced higher release of both TNF-α and IL-10. The results indicate that while LOS of NTHi has decreased capacity to induce pro-inflammatory responses compared to E. coli LPS or killed NTHi, this LOS has the potential to facilitate antigen presentation.Conclusions: Considering the important role of NTHi as a respiratory pathogen, and its currently increasing significance in the etiology of invasive infections, LOS deserves further attention as a vaccine antigen, which also has potent adjuvant properties.Keywords: Nontypeable Haemophilus influenzae, Lipooligosaccharide, THP-1 cells, innate immune responses

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Ketterer, Margaret R., Jian Q. Shao, Douglas B. Hornick, Ben Buscher, Venkata K. Bandi, and Michael A. Apicella. "Infection of Primary Human Bronchial Epithelial Cells by Haemophilus influenzae: Macropinocytosis as a Mechanism of Airway Epithelial Cell Entry." Infection and Immunity 67, no. 8 (August 1, 1999): 4161–70. http://dx.doi.org/10.1128/iai.67.8.4161-4170.1999.

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ABSTRACT Nontypeable Haemophilus influenzae is an exclusive human pathogen which infects the respiratory epithelium. We have initiated studies to explore the interaction of the nontypeableH. influenzae strain 2019 with primary human airway epithelial cells by electron and confocal microscopy. Primary human airway cell cultures were established as monolayers on glass collagen-coated coverslips or on semipermeable membranes at an air-fluid interface. Scanning electron microscopy indicated that bacteria adhered to nonciliated cells in the population. The surface of infected cells showed evidence of cytoskeletal rearrangements manifested by microvilli and lamellipodia extending toward and engaging bacteria. Confocal microscopic analysis demonstrated that infection induced actin polymerization with an increase in cortical actin as well as evidence of actin strands around the bacteria. Transmission electron microscopic analysis showed lamellipodia and microvilli surrounding organisms, as well as organisms adherent to the cell surface. These studies also demonstrated the presence of bacteria within vacuoles inside of airway cells. Confocal microscopic studies with Texas red-labeled dextran (molecular weight, 70,000) indicated that H. influenzae cells were entering cells by the process of macropinocytosis. These studies indicate that nontypeable H. influenzae can initiate cytoskeletal rearrangement within human airway epithelium, resulting in internalization of the bacteria within nonciliated human airway epithelial cells by the process of macropinocytosis.

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Harrison, Alistair, David W. Dyer, Allison Gillaspy, William C. Ray, Rachna Mungur, Matthew B. Carson, Huachun Zhong, et al. "Genomic Sequence of an Otitis Media Isolate of Nontypeable Haemophilus influenzae: Comparative Study with H. influenzae Serotype d, Strain KW20." Journal of Bacteriology 187, no. 13 (July 1, 2005): 4627–36. http://dx.doi.org/10.1128/jb.187.13.4627-4636.2005.

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ABSTRACT In 1995, the Institute for Genomic Research completed the genome sequence of a rough derivative of Haemophilus influenzae serotype d, strain KW20. Although extremely useful in understanding the basic biology of H. influenzae, these data have not provided significant insight into disease caused by nontypeable H. influenzae, as serotype d strains are not pathogens. In contrast, strains of nontypeable H. influenzae are the primary pathogens of chronic and recurrent otitis media in children. In addition, these organisms have an important role in acute otitis media in children as well as other respiratory diseases. Such strains must therefore contain a gene repertoire that differs from that of strain Rd. Elucidation of the differences between these genomes will thus provide insight into the pathogenic mechanisms of nontypeable H. influenzae. The genome of a representative nontypeable H. influenzae strain, 86-028NP, isolated from a patient with chronic otitis media was therefore sequenced and annotated. Despite large regions of synteny with the strain Rd genome, there are large rearrangements in strain 86-028NP's genome architecture relative to the strain Rd genome. A genomic island similar to an island originally identified in H. influenzae type b is present in the strain 86-028NP genome, while the mu-like phage present in the strain Rd genome is absent from the strain 86-028NP genome. Two hundred eighty open reading frames were identified in the strain 86-028NP genome that were absent from the strain Rd genome. These data provide new insight that complements and extends the ongoing analysis of nontypeable H. influenzae virulence determinants.

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Osorio-Aguilar, Yesenia, Maria Cristina Gonzalez-Vazquez, Patricia Lozano-Zarain, Ygnacio Martinez-Laguna, Alejandro Carabarin-Lima, and Rosa del Carmen Rocha-Gracia. "Cloning and Characterization of Immunological Properties of Haemophilus influenzae Enolase." Journal of Immunology Research 2021 (June 16, 2021): 1–14. http://dx.doi.org/10.1155/2021/6629824.

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Haemophilus influenzae is a common organism of the human upper respiratory tract; this bacterium is responsible of a wide spectrum for respiratory infections and can generate invasive diseases such as meningitis and septicemia. These infections are associated with H. influenzae encapsulated serotype b. However, the incidence of invasive disease caused by nontypeable H. influenzae (NTHi) has increased in the post-H. influenzae serotype b (Hib) vaccine era. Currently, an effective vaccine against NTHi is not available; due to this, it is important to find an antigen capable to confer protection against NTHi infection. In this study, 10 linear B cell epitopes and 13 CTL epitopes and a putative plasminogen-binding motif (252FYNKENGMY260) and the presence of enolase on the surface of different strains of H. influenzae were identified in the enolase sequence of H. influenzae. Both in silico and experimental results showed that recombinant enolase from H. influenzae is immunogenic that could induce a humoral immune response; this was observed mediating the generation of specific polyclonal antibodies anti-rNTHiENO that recognize typeable and nontypeable H. influenzae strains. The immunogenic properties and the superficial localization of enolase in H. influenzae, important characteristics to be considered as a new candidate for the development of a vaccine, were demonstrated.

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Novotny, Laura A., Kevin M. Mason, and Lauren O. Bakaletz. "Development of a Chinchilla Model To Allow Direct, Continuous, Biophotonic Imaging of Bioluminescent Nontypeable Haemophilus influenzae during Experimental Otitis Media." Infection and Immunity 73, no. 1 (January 2005): 609–11. http://dx.doi.org/10.1128/iai.73.1.609-611.2005.

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ABSTRACT We transformed a nontypeable Haemophilus influenzae clinical isolate with a plasmid containing the luxCDABE operon driven by the H. influenzae outer membrane protein P2 promoter. Herein, we demonstrate the ability to detect bioluminescence and to monitor infection within the nasopharynges, eustachian tubes, and middle ears of chinchillas after intranasal and transbullar challenges.

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Yang, Yan-ping, Sheena M. Loosmore, Brian J. Underdown, and Michel H. Klein. "Nasopharyngeal Colonization with Nontypeable Haemophilus influenzae in Chinchillas." Infection and Immunity 66, no. 5 (May 1, 1998): 1973–80. http://dx.doi.org/10.1128/iai.66.5.1973-1980.1998.

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ABSTRACT Colonization of the nasopharynx by a middle ear pathogen is the first step in the development of otitis media in humans. The establishment of an animal model of nasopharyngeal colonization would therefore be of great utility in assessing the potential protective ability of candidate vaccine antigens (especially adhesins) against otitis media. A chinchilla nasopharyngeal colonization model for nontypeable Haemophilus influenzae (NTHI) was developed with antibiotic-resistant strains. This model does not require coinfection with a virus. There was no significant difference in the efficiency of NTHI colonization between adult (1- to 2-year-old) and young (2- to 3-month-old) animals. However, the incidence of middle ear infection following nasopharyngeal colonization was significantly higher in young animals (83 to 89%) than in adult chinchillas (10 to 30%). Chinchillas that had recovered either from a previous middle ear infection caused by NTHI or from an infection by intranasal inoculation with NTHI were completely protected against nasopharyngeal colonization with a homologous strain and were found to be the best positive controls in protection studies. Systemic immunization of chinchillas with inactivated whole-cell preparations significantly protected animals not only against homologous NTHI colonization but also partially against heterologous NTHI infection. In all protected animals, significant serum anti-P6 and anti-HMW antibody responses were observed. The outer membrane P6 and high-molecular-weight (HMW) proteins appear to be promising candidate vaccine antigens to prevent nasopharyngeal colonization and middle ear infection caused by NTHI.

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Murphy, Timothy F., Howard Faden, Lauren O. Bakaletz, Jennelle M. Kyd, Arne Forsgren, Jose Campos, Mumtaz Virji, and Stephen I. Pelton. "Nontypeable Haemophilus influenzae as a Pathogen in Children." Pediatric Infectious Disease Journal 28, no. 1 (January 2009): 43–48. http://dx.doi.org/10.1097/inf.0b013e318184dba2.

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Kyd, Jennelle, and Allan Cripps. "Nontypeable Haemophilus influenzae: challenges in developing a vaccine." Journal of Biotechnology 73, no. 2-3 (August 1999): 103–8. http://dx.doi.org/10.1016/s0168-1656(99)00113-3.

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Kyd, Jennelle M., and Allan W. Cripps. "Towards a Protein Vaccine for Nontypeable Haemophilus influenzae." Clinical Infectious Diseases 28, no. 2 (February 1999): 238. http://dx.doi.org/10.1086/515119.

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Erwin, Alice L., and Arnold L. Smith. "Nontypeable Haemophilus influenzae: understanding virulence and commensal behavior." Trends in Microbiology 15, no. 8 (August 2007): 355–62. http://dx.doi.org/10.1016/j.tim.2007.06.004.

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Behrouzi, Ava, Farzam Vaziri, Fatemeh Rahimi-Jamnani, Parviz Afrough, Mohammad Rahbar, Fereshteh Satarian, and Seyed Davar Siadat. "Vaccine Candidates against Nontypeable Haemophilus influenzae: a Review." Iranian Biomedical Journal 21, no. 2 (March 1, 2017): 69–76. http://dx.doi.org/10.18869/acadpub.ibj.21.2.69.

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Bernstein, Joel M., Michael Belmont, Howard S. Faden, Diane Dryja, Frank Scannapieco, and Judy Wolf. "Interference of Nontypeable Haemophilus Influenzae and Moraxella Catarrhalis by Streptococcus Oralis in Adenoid Organ Culture: A Possible Strategy for the Treatment of the Otitis-Prone Child." Annals of Otology, Rhinology & Laryngology 111, no. 8 (August 2002): 696–700. http://dx.doi.org/10.1177/000348940211100807.

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The role of viridans group streptococci (Streptococcus oralis) in the prevention of colonization with nontypeable Haemophilus influenzae and Moraxella catarrhalis was investigated in an adenoid organ culture system. The adenoids from 100 patients who were undergoing adenoidectomy for either hypertrophy or recurrent otitis media were used. Streptococcus oralis Parker uniformly inhibited colonization with nontypeable H influenzae or M catarrhalis over a 24-hour period of incubation in adenoid organ culture. Streptococcus oralis Booth, a noninhibitory strain, did not significantly reduce colonization with nontypeable H influenzae and M catarrhalis. The results indicate that some strains of S oralis may inhibit colonization with potential pathogens in the nasopharynx. It is therefore possible that colonization with inhibitory strains of viridans streptococci may be used in the nasopharynx as a relatively safe and inexpensive approach to prevention of recurrent otitis media in some children.

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Green, Bruce A., Elizabeth Baranyi, Thomas J. Reilly, Arnold L. Smith, and Gary W. Zlotnick. "Certain Site-Directed, Nonenzymatically Active Mutants of the Haemophilus influenzae P4 Lipoprotein Are Able To Elicit Bactericidal Antibodies." Infection and Immunity 73, no. 7 (July 2005): 4454–57. http://dx.doi.org/10.1128/iai.73.7.4454-4457.2005.

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ABSTRACT The Haemophilus influenzae P4 lipoprotein (hel) is a potential component of a nontypeable H. influenzae otitis media vaccine. Since P4 is known to be an enzyme, nonenzymatically active forms of recombinant P4 are required. After site-directed mutagenesis of the hel gene, three of the mutated proteins were shown to be vaccine candidates.

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Murphy, Timothy F. "Vaccines for Nontypeable Haemophilus influenzae: the Future Is Now." Clinical and Vaccine Immunology 22, no. 5 (March 18, 2015): 459–66. http://dx.doi.org/10.1128/cvi.00089-15.

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ABSTRACTInfections due to nontypeableHaemophilus influenzaeresult in enormous global morbidity in two clinical settings: otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Recurrent otitis media affects up to 20% of children and results in hearing loss, delays in speech and language development and, in developing countries, chronic suppurative otitis media. Infections in people with COPD result in clinic and emergency room visits, hospital admissions, and respiratory failure. An effective vaccine would prevent morbidity, help control health care costs, and reduce antibiotic use, a major contributor to the global crisis in bacterial antibiotic resistance. The widespread use of the pneumococcal conjugate vaccines is causing a relative increase inH. influenzaeotitis media. The partial protection againstH. influenzaeotitis media induced by the pneumococcalH. influenzaeprotein D conjugate vaccine represents a proof of principle of the feasibility of a vaccine for nontypeableH. influenzae. An ideal vaccine antigen should be conserved among strains, have abundant epitopes on the bacterial surface, be immunogenic, and induce protective immune responses. Several surface proteins ofH. influenzaehave been identified as potential vaccine candidates and are in various stages of development. With continued research, progress toward a broadly effective vaccine to prevent infections caused by nontypeableH. influenzaeis expected over the next several years.

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Gönüllü, Erdem, Nesrin Özkan, Ahmet Soysal, Engin Acıoğlu, Emine Betül Tavil, Selin Nar Ötgün, and Metin Karaböcüoğlu. "Nontypeable Haemophilus influenzae Otitis Media: Mastoiditis and Meningitis Complicated with Central Venous Thrombosis in an Immunocompetent Child." Case Reports in Infectious Diseases 2021 (March 12, 2021): 1–5. http://dx.doi.org/10.1155/2021/8845200.

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Implementation of the Haemophilus influenzae type B (Hib) conjugate vaccine brought about a reduction in the number of cases and morbidity from type B but an increase in nontypeable strain infections. Nontypeable Haemophilus influenzae (NTHi) commonly colonizes children’s upper respiratory tract and causes otitis media, sinusitis, and bronchitis. Invasive NTHi diseases, such as meningitis and septicemia, have rarely been reported. Herein, we discuss a previously healthy, fully immunized 3-year-old girl presented with otitis media and mastoiditis leading to meningitis caused by NTHi complicated with central venous thrombosis. She was treated with antibiotics, mastoidectomy and ventilation tube insertion, and anticoagulation therapy and recovered uneventfully. Through this case, we wish to share our unique clinical experience that NTHi should be born in mind as a potential pathogen that can cause meningitis in previously healthy children, which may be helpful in future cases.

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Dawid, Suzanne, Susan Grass, and Joseph W. St. Geme. "Mapping of Binding Domains of NontypeableHaemophilus influenzae HMW1 and HMW2 Adhesins." Infection and Immunity 69, no. 1 (January 1, 2001): 307–14. http://dx.doi.org/10.1128/iai.69.1.307-314.2001.

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ABSTRACT Nontypeable Haemophilus influenzae is an important cause of localized respiratory tract disease, which begins with colonization of the upper respiratory mucosa. In previous work we reported that the nontypeable H. influenzae HMW1 and HMW2 proteins are high-molecular-weight nonpilus adhesins responsible for attachment to human epithelial cells, an essential step in the process of colonization. Interestingly, although HMW1 and HMW2 share significant sequence similarity, they display distinct cellular binding specificities. In order to map the HMW1 and HMW2 binding domains, we generated a series of complementary HMW1-HMW2 chimeric proteins and examined the ability of these proteins to promote in vitro adherence byEscherichia coli DH5α. Using this approach, we localized the HMW1 and HMW2 binding domains to an ∼360-amino-acid region near the N terminus of the mature HMW1 and HMW2 proteins. Experiments with maltose-binding protein fusion proteins containing segments of either HMW1 or HMW2 confirmed these results and suggested that the fully functional binding domains may be conformational structures that require relatively long stretches of sequence. Of note, the HMW1 and HMW2 binding domains correspond to areas of maximal sequence dissimilarity, suggesting that selective advantage associated with broader adhesive potential has been a major driving force duringH. influenzae evolution. These findings should facilitate efforts to develop a subcomponent vaccine effective against nontypeableH. influenzae disease.

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Alzbutienė, Giedrė, Ann Hermansson, Per Cayè-Thomasen, and Vytenis Kinduris. "Tympanic membrane changes in experimental acute otitis media and myringotomy." Medicina 44, no. 4 (April 20, 2008): 313. http://dx.doi.org/10.3390/medicina44040041.

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Objective. The present experimental study explored pathomorphological changes and calcium depositions in the tympanic membrane during experimental acute otitis media caused by nontypeable Haemophilus influenzae in myringotomized and nonmyringotomized ears. Material and methods. A rat model of experimental acute otitis media caused by nontypeable Haemophilus influenzae was employed. Sixteen Sprague-Dawley rats were used. Four days following middle ear inoculation, a bilateral myringotomy was performed in six randomly selected animals. Another group of 10 animals was inoculated only. On days 4, 7, 14, and 28 after inoculation, two animals from each group were sacrificed. The temporal bones were removed and the tympanic membranes were dissected, followed by paraffin embedding. Adjacent sections were stained with PAS-alcian blue for basic histopathological observations and by von Kossa method for determination of calcium phosphate depositions. Results. Particularly intense invasion of polymorphonuclear neutrophil leukocytes was seen on day 4 after inoculation. The highest infiltration of macrophages was observed on day 7. The peak number of lymphocytes was seen on day 14. No difference occurred in the number of polymorphonuclear leukocytes in myringotomized and nonmyringotomized tympanic membranes. The infiltration with lymphocytes and activated macrophages in all parts of the myringotomized tympanic membranes was statistically significantly higher than in the nonmyringotomized animals. The total amount of interstitial calcium phosphate depositions during days 7, 14, and 28 of study was statistically higher in the sections of pars tensa from myringotomized membranes compared to the nonmyringotomized membranes. Conclusion. Nontypeable Haemophilus influenzae-induced acute otitis media and myringotomy provoke more extensive inflammatory reaction with microcalcification in the tympanic membranes.

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Hartmann, Evamarie, Clifford A. Lingwood, and Joachim Reidl. "Heat-Inducible Surface Stress Protein (Hsp70) Mediates Sulfatide Recognition of the Respiratory Pathogen Haemophilus influenzae." Infection and Immunity 69, no. 5 (May 1, 2001): 3438–41. http://dx.doi.org/10.1128/iai.69.5.3438-3441.2001.

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ABSTRACT The in vitro glycolipid binding specificity of clinical strains of nontypeable Haemophilus influenzae is altered to include sulfated glycolipids following a brief heat shock. We have constructed, expressed, and purified a recombinant protein of H. influenzae Hsp70, which showed significant specific binding to sulfated galactolipids in vitro. Furthermore, indirect immunofluorescence demonstrates that Hsp70 proteins are surface exposed in H. influenzae only after heat shock and are contained in the outer membrane protein fractions.

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Ecevit, I. Zafer, Kirk W. McCrea, Carl F. Marrs, and Janet R. Gilsdorf. "Identification of New hmwA Alleles from Nontypeable Haemophilus influenzae." Infection and Immunity 73, no. 2 (February 2005): 1221–25. http://dx.doi.org/10.1128/iai.73.2.1221-1225.2005.

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ABSTRACT High-molecular-weight proteins of Haemophilus influenzae mediate attachment to epithelial cells. Previous reports describe several allelic versions of hmwA genes that have different adherence properties. Here we report three new alleles of hmwA (hmwA from strain AAr96, hmwA from strain AAr105, and hmwA from strain G822), demonstrating the high degree of DNA variation of these genes among different strains.

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Alikhan, Mir M., and F. Eun-Hyung Lee. "Understanding nontypeable Haemophilus influenzae and chronic obstructive pulmonary disease." Current Opinion in Pulmonary Medicine 20, no. 2 (March 2014): 159–64. http://dx.doi.org/10.1097/mcp.0000000000000023.

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Barenkamp, Stephen J. "A New Human Colonization Model for Nontypeable Haemophilus influenzae." Journal of Infectious Diseases 208, no. 5 (May 28, 2013): 717–19. http://dx.doi.org/10.1093/infdis/jit242.

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Daines, Dayle A., Mack H. Wu, and Sarah Y. Yuan. "VapC-1 of Nontypeable Haemophilus influenzae Is a Ribonuclease." Journal of Bacteriology 189, no. 14 (May 11, 2007): 5041–48. http://dx.doi.org/10.1128/jb.00290-07.

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ABSTRACT Nontypeable Haemophilus influenzae (NTHi) organisms are obligate parasites of the human upper respiratory tract that can exist as commensals or pathogens. Toxin-antitoxin (TA) loci are highly conserved gene pairs that encode both a toxin and antitoxin moiety. Seven TA gene families have been identified to date, and NTHi carries two alleles of the vapBC family. Here, we have characterized the function of one of the NTHi alleles, vapBC-1. The gene pair is transcribed as an operon in two NTHi clinical isolates, and promoter fusions display an inverse relationship to culture density. The antitoxin VapB-1 forms homomultimers both in vitro and in vivo. The expression of the toxin VapC-1 conferred growth inhibition to an Escherichia coli expression strain and was successfully purified only when cloned in tandem with its cognate antitoxin. Using total RNA isolated from both E. coli and NTHi, we show for the first time that VapC-1 is an RNase that is active on free RNA but does not degrade DNA in vitro. Preincubation of the purified toxin and antitoxin together results in the formation of a protein complex that abrogates the activity of the toxin. We conclude that the NTHi vapBC-1 gene pair functions as a classical TA locus and that the induction of VapC-1 RNase activity leads to growth inhibition via the mechanism of mRNA cleavage.

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Barenkamp, S. J. "Outer Membrane Proteins and Lipopolysaccharides of Nontypeable Haemophilus influenzae." Journal of Infectious Diseases 165, Supplement 1 (June 1, 1992): S181—S184. http://dx.doi.org/10.1093/infdis/165-supplement_1-s181.

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Fusté, M. C., M. A. Pineda, J. Palomar, M. Viñas, and J. G. Lorén. "Clonality of multidrug-resistant nontypeable strains of Haemophilus influenzae." Journal of clinical microbiology 34, no. 11 (1996): 2760–65. http://dx.doi.org/10.1128/jcm.34.11.2760-2765.1996.

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Lim, Mary E., Jill A. Hoffman, and Kwang Sik Kim. "Recurrent Ventriculoperitoneal Shunt Infection Due to Nontypeable Haemophilus influenzae." Clinical Infectious Diseases 28, no. 1 (January 1999): 147–48. http://dx.doi.org/10.1086/517182.

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St. Geme, Joseph W., Vini V. Kumar, David Cutter, and Stephen J. Barenkamp. "Prevalence and Distribution of the hmwand hia Genes and the HMW and Hia Adhesins among Genetically Diverse Strains of Nontypeable Haemophilus influenzae." Infection and Immunity 66, no. 1 (January 1, 1998): 364–68. http://dx.doi.org/10.1128/iai.66.1.364-368.1998.

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ABSTRACT Nontypeable Haemophilus influenzae is a common cause of human disease and initiates infection by colonizing the upper respiratory tract. In previous work we identified high-molecular-weight adhesins referred to as HMW1 and HMW2, expressed by nontypeable strain 12, and determined that most strains of nontypeable H. influenzae express one or two antigenically related proteins. More recently, we determined that some strains lack HMW1- and HMW2-like proteins and instead express an adhesin called Hia. In the present study, we determined the prevalence and distribution of thehmw and hia genes in a collection of 59 nontypeable strains previously characterized in terms of genetic relatedness. Based on Southern analysis, 47 strains contained sequences homologous to the hmw1 and hmw2 genes and nine strains contained homologs to hia. No strain harbored bothhmw and hia, and three strains harbored neither. Although the hmw and hia genes failed to define distinct genetic divisions, the hmw-deficient strains formed small clusters or lineages within the larger population structure. Additional analysis established that the IS1016insertion element was uniformly absent from strains containinghmw sequences but was present in two-thirds of thehmw-deficient strains. As IS1016 is associated with the capsule locus (cap) in most encapsulated strains of H. influenzae, we speculate thathmw-deficient nontypeable strains evolved more recently from an encapsulated ancestor.

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Kyd, Jennelle M., Allan W. Cripps, Laura A. Novotny, and Lauren O. Bakaletz. "Efficacy of the 26-Kilodalton Outer Membrane Protein and Two P5 Fimbrin-Derived Immunogens To Induce Clearance of Nontypeable Haemophilus influenzae from the Rat Middle Ear and Lungs as Well as from the Chinchilla Middle Ear and Nasopharynx." Infection and Immunity 71, no. 8 (August 2003): 4691–99. http://dx.doi.org/10.1128/iai.71.8.4691-4699.2003.

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ABSTRACT The rat middle ear and lung clearance model has been used to show that the nontypeable Haemophilus influenzae 26-kDa outer membrane protein OMP26 is highly efficacious as a mucosal immunogen, inducing significantly enhanced clearance in immunized rats upon direct challenge of these two anatomic sites. Similarly, the chinchilla model of middle ear and nasopharyngeal clearance has been used to show that two P5 fimbrin adhesin-derived immunogens, LB1 and lipoprotein D (LPD)-LB1(f)2,1,3, are highly efficacious as parenteral immunogens. Both induced significantly augmented clearance of nontypeable H. influenzae upon challenge of these sites. Here, these three nontypeable H. influenzae immunogens in addition to six bovine serum albumin and keyhole limpet hemocyanin conjugates of the synthetic peptide LB1(f) were assayed for relative efficacy in the reciprocal rodent model system. OMP26 was assayed in the chinchilla host by a parenteral immunization route, with clearance of the middle ear and nasopharynx used as outcome measures. Both LB1 and LPD-LB1(f)2,1,3 were assayed in the rat host with a mucosal immunization route and clearance of nontypeable H. influenzae from the lungs and middle ears as outcome measures. Both of the immunogens were found to induce a high-titered and specific immune responses in the heterologous host system. Moreover, each was found to be highly efficacious in the reciprocal host system, providing strong support for the continued development and inclusion of both OMP26 and P5 fimbrin-derived peptides as candidate vaccine antigens directed at otitis media caused by nontypeable H. influenzae.

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Hu, Fang, Lavanya Rishishwar, Ambily Sivadas, Gabriel J. Mitchell, I. King Jordan, Timothy F. Murphy, Janet R. Gilsdorf, Leonard W. Mayer, and Xin Wang. "Comparative Genomic Analysis of Haemophilus haemolyticus and Nontypeable Haemophilus influenzae and a New Testing Scheme for Their Discrimination." Journal of Clinical Microbiology 54, no. 12 (October 5, 2016): 3010–17. http://dx.doi.org/10.1128/jcm.01511-16.

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Haemophilushaemolyticushas been recently discovered to have the potential to cause invasive disease. It is closely related to nontypeableHaemophilus influenzae(NTH. influenzae). NTH. influenzaeandH. haemolyticusare often misidentified because none of the existing tests targeting the known phenotypes ofH. haemolyticusare able to specifically identifyH. haemolyticus. Through comparative genomic analysis ofH. haemolyticusand NTH. influenzae, we identified genes unique toH. haemolyticusthat can be used as targets for the identification ofH. haemolyticus. A real-time PCR targetingpurT(encoding phosphoribosylglycinamide formyltransferase 2 in the purine synthesis pathway) was developed and evaluated. The lower limit of detection was 40 genomes/PCR; the sensitivity and specificity in detectingH. haemolyticuswere 98.9% and 97%, respectively. To improve the discrimination ofH. haemolyticusand NTH. influenzae, a testing scheme combining two targets (H. haemolyticuspurTandH. influenzaehpd, encoding protein D lipoprotein) was also evaluated and showed 96.7% sensitivity and 98.2% specificity for the identification ofH. haemolyticusand 92.8% sensitivity and 100% specificity for the identification ofH. influenzae, respectively. The dual-target testing scheme can be used for the diagnosis and surveillance of infection and disease caused byH. haemolyticusand NTH. influenzae.

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Allen, Simon, Anthony Zaleski, Jason W. Johnston, Bradford W. Gibson, and Michael A. Apicella. "Novel Sialic Acid Transporter of Haemophilus influenzae." Infection and Immunity 73, no. 9 (September 2005): 5291–300. http://dx.doi.org/10.1128/iai.73.9.5291-5300.2005.

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ABSTRACT Nontypeable Haemophilus influenzae is an opportunistic pathogen and a common cause of otitis media in children and of chronic bronchitis and pneumonia in patients with chronic obstructive pulmonary disease. The lipooligosaccharides, a major component of the outer membrane of H. influenzae, play an important role in microbial virulence and pathogenicity. N-Acetylneuraminic acid (sialic acid) can be incorporated into the lipooligosaccharides as a terminal nonreducing sugar. Although much of the pathway of sialic acid incorporation into lipooligosaccharides is understood, the transporter responsible for N-acetylneuraminic acid uptake in H. influenzae has yet to be characterized. In this paper we demonstrate that this transporter is a novel sugar transporter of the tripartite ATP-independent periplasmic transporter family. In the absence of this transporter, H. influenzae cannot incorporate sialic acid into its lipooligosaccharides, making the organism unable to survive when exposed to human serum and causing reduced viability in biofilm growth.

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Tristram, Stephen, Michael R. Jacobs, and Peter C. Appelbaum. "Antimicrobial Resistance in Haemophilus influenzae." Clinical Microbiology Reviews 20, no. 2 (April 2007): 368–89. http://dx.doi.org/10.1128/cmr.00040-06.

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SUMMARY Haemophilus influenzae is a major community-acquired pathogen causing significant morbidity and mortality worldwide. Meningitis and bacteremia due to type b strains occur in areas where the protein-conjugated type b vaccine is not in use, whereas nontypeable strains are major causes of otitis media, sinusitis, acute exacerbations of chronic bronchitis, and pneumonia. Antibiotic resistance in this organism is more diverse and widespread than is commonly appreciated. Intrinsic efflux resistance mechanisms limit the activity of the macrolides, azalides, and ketolides. β-Lactamase production is highly prevalent worldwide and is associated with resistance to ampicillin and amoxicillin. Strains with alterations in penicillin binding proteins, particularly PBP3 (β-lactamase negative ampicillin resistant and β-lactamase positive amoxicillin-clavulanate resistant), are increasing in prevalence, particularly in Japan, with increasing resistance to ampicillin, amoxicillin, amoxicillin-clavulanate, and many cephalosporins, limiting the efficacy of expanded-spectrum cephalosporins against meningitis and of many oral cephalosporins against other diseases. Most strains remain susceptible to the carbapenems, which are not affected by penicillin binding protein changes, and the quinolones. The activity of many oral agents is limited by pharmacokinetics achieved with administration by this route, and the susceptibility of isolates based on pharmacokinetic and pharmacodynamic parameters is reviewed.

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Wong, Sandy M. S., Frank St. Michael, Andrew Cox, Sanjay Ram, and Brian J. Akerley. "ArcA-Regulated Glycosyltransferase Lic2B Promotes Complement Evasion and Pathogenesis of Nontypeable Haemophilus influenzae." Infection and Immunity 79, no. 5 (February 28, 2011): 1971–83. http://dx.doi.org/10.1128/iai.01269-10.

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ABSTRACTSignaling mechanisms used byHaemophilus influenzaeto adapt to conditions it encounters during stages of infection and pathogenesis are not well understood. The ArcAB two-component signal transduction system controls gene expression in response to respiratory conditions of growth and contributes to resistance to bactericidal effects of serum and to bloodstream infection byH. influenzae. We show that ArcA of nontypeableH. influenzae(NTHI) activates expression of a glycosyltransferase gene,lic2B.Structural comparison of the lipooligosaccharide (LOS) of alic2Bmutant to that of the wild-type strain NT127 revealed thatlic2Bis required for addition of a galactose residue to the LOS outer core. Thelic2Bgene was crucial for optimal survival of NTHI in a mouse model of bacteremia and for evasion of serum complement. The results demonstrate that ArcA, which controls cellular metabolism in response to environmental reduction and oxidation (redox) conditions, also coordinately controls genes that are critical for immune evasion, providing evidence that NTHI integrates redox signals to regulate specific countermeasures against host defense.

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McCrea, K. W., J. Xie, N. LaCross, M. Patel, D. Mukundan, T. F. Murphy, C. F. Marrs, and J. R. Gilsdorf. "Relationships of Nontypeable Haemophilus influenzae Strains to Hemolytic and Nonhemolytic Haemophilus haemolyticus Strains." Journal of Clinical Microbiology 46, no. 2 (November 26, 2007): 406–16. http://dx.doi.org/10.1128/jcm.01832-07.

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Faden, Howard, Thomas Foels, Linda Duffy, and Jung J. Hong. "Adherence of Nontypeable Haemophilus Influenzae to Respiratory Epithelium of Otitis-Prone and Normal Children." Annals of Otology, Rhinology & Laryngology 105, no. 5 (May 1996): 367–70. http://dx.doi.org/10.1177/000348949610500507.

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Three hundred six children were enrolled at birth in a prospective study of otitis media and followed up for 2 years. Adherence of nontypeable Haemophilus influenzae to buccal epithelial cells was compared between otitis-prone children and age- and sex-matched normal controls at birth, 1 year, and 2 years. The mean ± SD/median percent adherence was similar for the two groups at birth (1.6 ± 2.3/1.0 versus 1.2 ± 1.4/1.0; NS) and at 2 years (1.6 ± 1.7/1.5 versus 2.1 ±2.1/1.5; NS). At 1 year of age the adherence rate for the otitis-prone group (2.4 ± 2.6/1.0) was statistically greater than that for the control group (1.0 ± 1.3/0.0; p < .02). Because this difference is probably clinically insignificant, other explanations must be sought for the increased colonization rates of nontypeable H influenzae observed in otitis-prone children.

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Journal articles on the topic 'Nontypeable Haemophilus influenzae'

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