Dissertations / Theses on the topic 'Host-bacterial interaction'
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de, Klerk Nele. "Host-bacteria interactions : Host cell responses and bacterial pathogenesis." Doctoral thesis, Stockholms universitet, Institutionen för molekylär biovetenskap, Wenner-Grens institut, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-126425.
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Helicobacter pylori colonizes the human stomach, where it causes gastritis that may develop into peptic ulcer disease or cancer when left untreated. Neisseria gonorrhoeae colonizes the urogenital tract and causes the sexually transmitted disease gonorrhea. In contrast, Lactobacillus species are part of the human microbiota, which is the resident microbial community, and are considered to be beneficial for health. The first host cell types that bacteria encounter when they enter the body are epithelial cells, which form the border between the inside and the outside, and macrophages, which are immune cells that engulf unwanted material. The focus of this thesis has been the interaction between the host and bacteria, aiming to increase our knowledge of the molecular mechanisms that underlie the host responses and their effects on bacterial pathogenicity. Understanding the interactions between bacteria and the host will hopefully enable the development of new strategies for the treatment of infectious disease. In paper I, we investigated the effect of N. gonorrhoeae on the growth factor amphiregulin in cervical epithelial cells and found that the processing and release of amphiregulin changes upon infection. In paper II, we examined the expression of the transcription factor early growth response-1 (EGR1) in epithelial cells during bacterial colonization. We demonstrated that EGR1 is rapidly upregulated by many different bacteria. This upregulation is independent of the pathogenicity, Gram-staining type and level of adherence of the bacteria, but generally requires viable bacteria and contact with the host cell. The induction of EGR1 is mediated primarily by signaling through EGFR, ERK1/2 and β1-integrins. In paper III, we described the interactions of the uncharacterized protein JHP0290, which is secreted by H. pylori, with host cells. JHP0290 is able to bind to several cell types and induces apoptosis and TNF release in macrophages. For both of these responses, signaling through Src family kinases and ERK is essential. Apoptosis is partially mediated by TNF release. Finally, in paper IV, we showed that certain Lactobacillus strains can reduce the colonization of H. pylori on gastric epithelial cells. Lactobacilli decrease the gene expression of SabA and thereby inhibit the binding mediated by this adhesin.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 4: Manuscript.
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Shah, Samir Ashok. "The Effect of Smoking on Host-Bacterial Interaction." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1338316888.
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Akpa, Abubakar Dominic. "Host-parasite interaction in bacterial blight of pea caused by Pseudomonas syringae pv. pisi." Thesis, Imperial College London, 1989. http://hdl.handle.net/10044/1/47328.
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Aljannat, Mahab. "Bacterial moonlighting proteins of N. meningitidis : interaction with the host and role in pathogenesis." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/41073/.
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Neisseria meningitidis is a human-restricted pathogen that colonizes the nasopharynx, mostly without causing any disease. However, bacteria can invade into the bloodstream and cross the blood brain barrier resulting in life threatening sepsis and meningitis. Protein moonlighting is a concept established to describe the additional task(s) that a protein exhibits alongside its canonical function. After translocation to the cell surface by an unknown mechanism, moonlighting proteins may interact with various host proteins, and exhibit virulence-associated functions. Enolase (Eno), peroxiredoxin (Prx) and DnaK are meningococcal housekeeping proteins that are functionally described as a glycolytic enzyme, an anti-oxidant protein and a molecular chaperon, respectively. They have been identified on the surface of meningococci achieving non-housekeeping (moonlighting) functions related to interactions with the human protein plasminogen. This study sheds light on the moonlighting properties of these three proteins in the pathogenesis of meningococcal disease. Meningococcal Eno, Prx and DnaK were cloned, overexpressed in E. coli cells, and the corresponding wild type recombinant proteins were affinity purified under non-denaturing conditions. The oligomerization status of each recombinant protein was determined by analytical gel filtration, in which rEno was identified as an octamer, rPrx as a hexamer and rDnaK was either in a dimeric or monomeric state. Polyclonal antiserum targeted against each recombinant protein was raised in rabbits. A markerless pxn-knockout was generated in N. meningitidis MC58 rpsL-. The streptomycin resistance phenotype that the rpsL- allele confers was the basis behind the adopted mutation strategy. To delete NMB0946 (encoding meningococcal Prx), two mutagenic plasmids (pGUD2 and pGUD3) were constructed to allow two homologous recombination events. N. meningitidis rpsL- ∆pxn KanR rpsL+ was the resultant strain from the first event. The second homologous recombination event, facilitated by pGUD3, involved removing the selectable marker (KanR plus rpsL+ allele) to generate the markerless N. meningitidis rpsL- ∆pxn. Given that NMB0946 is part of a two-gene operon necessitated the construction of a complementation strain, in which a wild type copy of NMB0946 was reintroduced at an ectopic site of N. meningitidis rpsL- ∆pxn genome to complement that deletion. Using equimolar amounts of the recombinant proteins in EIA assays, it was found that meningococcal rEno binds plasminogen (Plg) more strongly than rDnaK and rPrx. Plg binding was inhibited when the lysine analogue ϵ-aminocapronic acid was added suggesting the potential involvement of lysine residues. Substitution of the C-terminal lysine residues of rEno, rPrx and rDnaK with alanine residues, significantly yet not completely, reduced binding to Plg. For rEno, lysine residues at positions 297 and 355 were identified for the first time as additional sites for Plg. rPrx with mutation in the active cysteine site (rPrx185CA), which is known to inactivate the protein, was able to bind Plg to the same level as the wild type strain. Unlike the C-terminal lysine residues, substituting the sub-terminal lysines of rPrx and rDnaK (at positions 230 and 641, respectively) did not alter binding to Plg. Employing whole-cell EIA, Prx and DnaK could be detected on the surface of wild-type encapsulated N. meningitidis MC58, while surface localisation of Eno was not detected under these conditions. Under hydrogen peroxide-mediated oxidative stress, the N. meningitidis ∆pxn-mutant survived remarkably better than the parental strain. Using human whole blood as a model of meningococcal bacteraemia, it was found that N. meningitidis ∆pxn-mutant has a survival defect compared with the wild-type strain. Preliminary data suggest that the survival of the ∆pxn-mutant cells in the presence of polymorphonuclear leukocytes (PMNs) isolated from peripheral blood was similar to controls containing no PMNs. Moreover, the absence of Prx could not significantly reduce the ability of whole meningococcal cells to bind Plg. In summary, the data suggest that Eno, Prx and DnaK bind plasminogen mainly via the C-terminal lysine residues. Lysine 297 and 355 of rEno are required for optimal Plg binding. The canonical and the moonlighting functions of meningococcal Prx are independent. This study also proposes that the absence of Prx does not impair overall Plg binding, has a positive impact on the ability of meningococci to tolerate exogenous hydrogen peroxide, and finally, has a very significant effect on the survival of meningococcal cells in human whole blood.
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Maldonado-Arocho, Francisco J. "Characterization of host-pathogen interaction of two bacterial toxins anthrax edema toxin and Escherichia coli cytolethal distending toxin /." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1973060671&sid=4&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Lopez, Fernandez Juan Sebastian [Verfasser], and Michael [Akademischer Betreuer] Steinert. "Molecular ecological interaction of bacterial endophytes with their host Vitis vinifera (L) / Juan Sebastian Lopez Fernandez ; Betreuer: Michael Steinert." Braunschweig : Technische Universität Braunschweig, 2017. http://d-nb.info/1175817228/34.
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Lopez, Fernandez Juan Sebastian Verfasser], and Michael [Akademischer Betreuer] [Steinert. "Molecular ecological interaction of bacterial endophytes with their host Vitis vinifera (L) / Juan Sebastian Lopez Fernandez ; Betreuer: Michael Steinert." Braunschweig : Technische Universität Braunschweig, 2017. http://nbn-resolving.de/urn:nbn:de:gbv:084-2017072708547.
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Shekhar, Sudhanshu. "A study on the role of lung dendritic cells and their interaction with innate lymphocytes in host defense against a bacterial lung infection." Karger, 2015. http://hdl.handle.net/1993/30622.
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Chlamydia is an obligate intracellular bacterial pathogen that causes a wide spectrum of diseases worldwide. At present, there are no vaccines to prevent chlamydial infections due to poor understanding of how anti-chlamydial immunity ensues. In this study, we employed a variety of in vitro and in vivo systems, including knockout (KO) mice and adoptive transfer, to investigate the role of lung dendritic cells (LDCs) and their relationship with innate lymphocytes, natural killer (NK) and invariant NKT (iNKT) cells, in host defense against chlamydial lung infections in mice. We found that iNKT cells altered the phenotype and cytokine production pattern of LDCs following C. pneumoniae infection. Adoptive transfer of LDCs from infected Jα18-KO mice, which lack iNKT cells, into naïve wild-type (WT) mice promoted Th2 (IL-4) immunity following infection challenge, whereas the transfer of LDCs from the infected WT mice induced protective Th1/Tc1 (IFN-γ) immunity. On the other hand, upon adoptive transfer, LDCs from C. muridarum-infected NK-cell-depleted mice (NK-LDCs) conferred reduced protection after chlamydial challenge than the recipients of LDCs from infected sham-treated mice (NK+LDCs). NK+LDC recipients exhibited an enhanced Th1/Th17, in contrast to Th2, response compared to the NK-LDC recipients. In coculture experiments, NK cells isolated from the infected mice promoted IL-12p70, IL-6, and IL-23 production by LDCs through NKG2D receptor signaling. These findings indicate that iNKT and NK cells condition LDCs to confer protective Th1/Tc1/Th17 immunity against chlamydial lung infection.
We also analyzed the contribution of major LDC subsets, CD103+ and CD11bhi LDCs, in host defense against C. muridarum infection. We found that CD103+ and CD11bhi LDC subsets expanded following chlamydial infection. CD103+ LDCs showed higher expression of costimulatory molecules and greater production of Th1- and Th17-inducing cytokines (IL-12, IL-6 and IL-23) than CD11bhi LDCs. Coculture of Chlamydia-specific CD4+ T cells with LDC subsets revealed that the T cells cultured with CD103+ LDCs produced larger amounts of IFN-γ and IL-17 compared to those with CD11bhi LDCs. To test their function in vivo, we isolated CD103+ and CD11bhi LDC subsets from infected mice and transferred them into naïve syngeneic mice that received chlamydial challenge. CD103+ LDC-recipients showed better protection, as evidenced by their reduced body weight loss, bacterial burden and lung pathology, than CD11bhi LDC recipients. Mice that received CD103+, compared to CD11bhi, LDCs produced enhanced Th1/Th17 cytokines (IFN-γ and IL-17) in the lung and the MLNs. In conclusion, these findings demonstrate that CD103+ LDCs are more efficient in inducing Th1/Th17 immunity to chlamydial infection than CD11bhi LDCs.
Taken together, our findings have provided direct in vivo evidence on the role of LDCs and their conditioning by iNKT and NK cells in generating mucosal T-cell immunity against a bacterial lung infection. The findings have added new knowledge to the field of lung immunology, which have implications for developing prophylactic and/or therapeutic strategies against respiratory diseases.October 2015
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Yan, Shuangchun. "Using the Bacterial Plant Pathogen Pseudomonas syringae pv. tomato as a Model to Study the Evolution and Mechanisms of Host Range and Virulence." Diss., Virginia Tech, 2010. http://hdl.handle.net/10919/77293.
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Most plant pathogens are specialists where only few plant species are susceptible, while all other plants are resistant. Unraveling the mechanisms behind this can thus provide valuable information for breeding or engineering crops with durable disease resistance. A group of Pseudomonas syringae strains with different host ranges while still closely related were thus chosen for comparative study. We confirmed their close phylogenetic relationship. We found evidence supporting that these strains recombined during evolution. The Arabidopsis thaliana and tomato pathogen P. syringae pv. tomato (Pto) DC3000 was found to be an atypical tomato strain, distinct from the typical Pto strains commonly isolated in the field that do not cause disease in A. thaliana, such as Pto T1. Comparing A. thaliana defense responses to DC3000 and T1, we found that T1 is eliciting stronger responses than DC3000. T1 is likely lacking Type III effector genes necessary to suppress plant defense. To test this, we sequenced the genomes of strains that cause and do not cause disease in A. thaliana. Comparative genomics revealed candidate effector genes responsible for this host range difference. Effector genes conserved in strains pathogenic in A. thaliana were expressed in T1 to test whether they would allow T1 to growth better in A. thaliana. Surprisingly, most of them reduced T1 growth. One of the effectors, HopM1, was of particular interest because it is disrupted in typical Pto strains. Although HopM1 has known virulence function in A. thaliana, HopM1 reduced T1 growth in both A. thaliana and tomato. HopM1 also increased the number of bacterial specks but reduced their average size in tomato. Our data suggest that HopM1 can trigger defenses in these plants. Additionally, transgenic detritivore Pseudomonas fluorescens that can secrete HopM1 shows dramatically increased growth in planta. The importance of genetic background of the pathogen for the functions of individual effectors is discussed. T1 cannot be manipulated to become an A. thaliana pathogen by deleting or adding individual genes. We now have a list of genes that can be studied in the future for the molecular basis of host range determination.Ph. D.
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Dorling, Jack. "Peptidoglycan recycling in the Gram-positive bacterium Staphylococcus aureus and its role in host-pathogen interaction." Thesis, University of Oxford, 2018. http://ora.ox.ac.uk/objects/uuid:3fc4f926-296d-43a1-bb45-af9f37a87d8d.
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Bacteria are enclosed by a peptidoglycan sacculus, an exoskeleton-like polymer composed of glycan strands cross-linked by short peptides. The sacculus surrounds the cell in a closed bag-like structure and forms the main structural component of the bacterial cell wall. As bacteria grow and divide, cell wall remodelling by peptidoglycan hydrolases results in the release of peptidoglycan fragments from the sacculus. In Gram-negative bacteria, these fragments are efficiently trapped and recycled. Gram-positive bacteria however shed large quantities of peptidoglycan fragments into the environment. For nearly five decades, Gram-positive bacteria were thus assumed not to recycle peptidoglycan and this process has remained enigmatic until recently. In this thesis, the occurrence and physiological role of peptidoglycan recycling in the Gram-positive pathogen Staphylococcus aureus was investigated. S. aureus is an important pathogen, and is becoming increasingly resistant to many antibiotics. Through bioinformatic and experimental means it was determined that S. aureus may potentially recycle components of peptidoglycan and novel peptidoglycan recycling components were identified and characterised. Though disruption of putative peptidoglycan recycling in S. aureus appears not affect growth or gross morphology of this bacterium, potential roles for peptidoglycan recycling in cell wall homeostasis and in virulence were identified. This is to my knowledge the first demonstration of a potential role of peptidoglycan recycling in either of these aspects of bacterial physiology in any Gram-positive bacterium. This is an important step forward in understanding the basic biology of Gram-positive bacteria, and in understanding the mechanisms of virulence in S. aureus. Future study of this process in S. aureus and other Gram-positive bacteria promises to reveal yet further facets of this process and its functions, potentially leading to the identification of novel therapeutic approaches to combat infections.
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Batista, Diego Felipe Alves [UNESP]. "Avaliação da patogenicidade de estirpes mutantes de Salmonella Gallinarum biovar Gallinarum para genes relacionados ao metabolismo naturalmente defectivos em S. Gallinarum biovar Pullorum." Universidade Estadual Paulista (UNESP), 2017. http://hdl.handle.net/11449/151213.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
O tifo aviário, causado por Salmonella Gallinarum biotipo Gallinarum, é uma infecção caracterizada pela alta mortalidade nos lotes de aves suscetíveis acometidos, enquanto S. Gallinarum biotipo Pullorum, o agente da pulorose, infecta as aves de produção industrial com as quais desenvolve relação mais branda. Ainda é escasso o conhecimento sobre os mecanismos moleculares que sustentam essas diferentes interações patógeno-hospedeiro. Nesse estudo, objetivou-se investigar o efeito de deleção parcial das sequências codificantes dos genes idnT (transportador de L-idonato ou D-gluconato), idnO (5-cetogluconato redutase) e ccmH (heme liase necessária na montagem de citocromos do tipo C) sobre a patogenicidade de S. Gallinarum 287/91 (SG287/91), uma vez que seus ortólogos são pseudogenes conservados em S. Pullorum. Os clones mutantes SG∆idnTO, SG∆ccmH e SG∆ccmHidnTO foram obtidos por meio da técnica de mutação sítio-dirigida, denominada de recombinação Lambda-Red e testados em dois experimentos independentes com aves comerciais semipesadas de postura suscetíveis ao tifo aviário. No 1º experimento não se observou alteração da patogenicidade dos clones mutantes após inoculação oral, pois todos os animais infectados desenvolveram sinais clínicos típicos do tifo aviário e vieram a óbito ao longo de 12 dias pós-infecção (dpi). Apesar dos 100% de mortalidade, as infecções desenvolvidas pelos clones SG∆idnTO e SG∆ccmHidnTO levaram os animais a óbito dentro de 48 horas desde o aparecimento dos sinais clínicos, enquanto SG287/91 o fez em 6 dias, sugerindo aumento da virulência dos clones mutantes. No 2º experimento observou-se que as mutantes invadiram o hospedeiro a partir do intestino, embora as quantidades recuperadas de SG∆idnTO e SG∆ccmHidnTO nos fígados e de SG∆idnTO nos baços, no 5º dpi, foram superiores a de SG287/91, reforçando a hipótese de aumento da virulência dos clones contendo a alteração idnTO. Apesar disso, os níveis de transcrição das citocinas CXCLi2 e IL6 produzidos à infecção por SG∆idnTO e SG∆ccmHidnTO não diferiram nas tonsilas cecais nos 1º e 3º dpi e nos baços no 3º dpi em relação à infecção por SG287/91. Somente SG∆ccmH inclinou-se a estimular a transcrição de CXCLi2 e IL6 nas tonsilas cecais no 1° dpi em relação ao grupo controle, enquanto SG287/91 tendeu a suprimi-la. Porém, não houve suporte estatístico para essa observação. Os níveis de mRNA do IFNγ estavam aumentados para todas as estirpes de S. Gallinarum, mutantes ou não, porém sem diferença estatística entre eles. Os resultados do presente estudo indicam que a ruptura nos genes idnTO, e em menor grau do gene ccmH, poderiam levar a perda de “fitness” em S. Gallinarum, lhes justificando a permanência no genoma desse micro-organismo, ao contrário do que ocorre com S. Pullorum. O estudo da patogenicidade de estirpe de S. Pullorum tendo reconstituídos os genes idnTO e ccmH no seu genoma poderia esclarecer os motivos pelos quais esses foram negativamente selecionados por esse micro-organismo.
Fowl typhoid, caused by Salmonella Gallinarum biovar Gallinarum, is an infectious disease which elicits high mortality into a flock of susceptible birds whereas S. Gallinarum biovar Pullorum, the aetiological agent of pullorum disease, infects poultry of commercial importance with which such a bacterium sets off a more permissive host-pathogen interaction. Little is known about the molecular mechanisms driving these distinct interplays with the host. Herein, we aimed at investigating the effect of partial deletions in the idnT (L-idonate / D-gluconate transporter), idnO (5-ketogluconase reductase) and ccmH (heme liase involved in the c-type cytochrome maturation) coding sequences on S. Gallinarum 287/91 (SG287/91) pathogenicity since they are conserved pseudogenes in S. Pullorum genomes. SG∆idnTO, SG∆ccmH and SG∆ccmHidnTO mutant strains were constructed through a one-step inactivation technique, known as Lambda-Red-mediated recombination, and tested on two independent experiments by using a commercial brown egg-producing layer line susceptible to fowl typhoid. On the experiment 1, no changing was observed in the pathogenicity of the mutant strains upon oral inoculation as the infected animals developed typical fowl typhoid clinical signs and died along 12 days post-infection (dpi). In spite of causing 100% mortality, SG∆idnTO and SG∆ccmHidnTO killed all the animals within 48 hours since the clinical signs appearance while SG287/91 did so in 6 days, indicating an increased virulence by these mutant strains. On the experiment 2 every mutant strain were able to invade the host system from the intestine albeit SG∆idnTO and SG∆ccmHidnTO were recovered from livers and SG∆idnTO alone from spleens at higher numbers than was SG287/91, supporting the hypothesis of increased virulence for those clones harbouring the idnTO mutation. Despite the results above, CXCLi2 and IL6 transcription levels during infection by SG∆idnTO and SG∆ccmHidnTO were similar to that induced by SG287/91 in caecal tonsils at 1 and 3 dpi and in spleens at 3 dpi. In contrast, SG∆ccmH trended to stimulate CXCLi2 and IL6 transcription in caecal tonsils at 1 dpi when compared to the negative, control group whereas SG287/91 tended to suppress it, but no statistical significance was found for such an observation. IFNγ mRNA were augmented for all S. Gallinarum strains, mutant or not, but without statistical difference amongst them. These findings indicate that gene decay into idnTO, and at a lesser extent, into ccmH sequences might lead to the loss of fitness by S. Gallinarum, raising an explanation for their maintenance on this bacterium chromosome when the opposite happens to S. Pullorum. Studying the pathogenicity of a S. Pullorum strain possessing both the idnTO and ccmH genes in its genome could bring to light the reasons whereby such genes were negatively selected by this microorganism.
FAPESP: 2013/22920-4
FAPESP: 2013/26127-7
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Cossé, Mathilde. "Identification et caractérisation d'un nouvel effecteur précoce de Chlamydia trachomatis." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066083/document.
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C. trachomatis est une bactérie Gram-négative intracellulaire obligatoire et un pathogène humain. Première cause de maladie sexuellement transmissible d'origine bactérienne, elle est également responsable, dans les pays en développement, d'infections oculaires pouvant conduire à la cécité (trachome). Son cycle de développement bi-phasique a lieu au sein d'un compartiment appelé inclusion. Grâce à un système de sécrétion de type 3 (SST3), Chlamydia sécrète des protéines dans le cytosol de la cellule afin de promouvoir sa survie et sa multiplication. Ces protéines sont désignées sous le terme d'effecteursC. trachomatis is an obligate intracellular Gram-negative bacteria and a human pathogen. It is the most prevalent cause of sexually transmitted diseases of bacterial origin and a leading cause of preventable blindness in the developing world. During their biphasic developmental cycle the bacteria remains in a membrane-bounded cellular compartment called an inclusion. Using a type 3 secretion system (T3SS) they translocate effector proteins inside the cytosol of the cell to promote its survival and multiplication.The aim of the PhD was to study the function of CT622, a hypothetic protein from C. trachomatis. We showed that CT622 is an effector protein from the T3SS and that it is secreted early during the infection. We identified a bacterial protein that binds to CT622, and we showed that it acts as a chaperone, stabilizing CT622 and enhancing its secretion. We obtained bacteria lacking CT622 expression, thus demonstrating that CT622 is not essential for bacterial growth in vitro. However, preliminary studies indicate that in the absence of CT622 bacterial development is delayed and T3SS is defective.We identified several molecules interacting with CT622: geranylgeranyl diphosphate, Rab39 and Atg16L1 proteins. Future work will aim at understanding how these identified interactions, or other bacterial or cellular partners still to be discovered, contribute to the establishment of a niche favorable to bacterial development
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Venkatesh, Balakrishnan. "Characterization of bacterial Lipopolysaccharides (Pseudomonas syringae pv. tomato and Pseudomonas syringae pv. apii) and pectins of tomato and celery plants (Lycopersicon esculentum and Apium graveolens) regarding their possible rolle in host, pathogen interaction." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=966627423.
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Raffetseder, Johanna. "Interplay of human macrophages and Mycobacterium tuberculosis phenotypes." Doctoral thesis, Linköpings universitet, Avdelningen för mikrobiologi och molekylär medicin, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-132321.
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Mycobacterium tuberculosis (Mtb) is the pathogen causing tuberculosis (TB), a disease most often affecting the lung. 1.5 million people die annually due to TB, mainly in low-income countries. Usually considered a disease of the poor, also developed nations recently put TB back on their agenda, fueled by the HIV epidemic and the global emergence of drug-resistant Mtb strains. HIV-coinfection is a predisposing factor for TB, and infection with multi-drug resistant and extremely drug resistant strains significantly impedes and lengthens antibiotic treatment, and increases fatality. Mtb is transmitted from a sick individual via coughing, and resident macrophages are the first cells to encounter the bacterium upon inhalation. These cells phagocytose intruders and subject them to a range of destructive mechanisms, aiming at killing pathogens and protecting the host. Mtb, however, has evolved to cope with host pressures, and has developed mechanisms to submerge macrophage defenses. Among these, inhibition of phagosomal maturation and adaptation to the intracellular environment are important features. Mtb profoundly alters its phenotype inside host cells, characterized by altered metabolism and slower growth. These adaptations contribute to the ability of Mtb to remain dormant inside a host during latent TB infection, a state that can last for decades. According to recent estimates, one third of the world’s population is latently infected with Mtb, which represents a huge reservoir for active TB disease. Mtb is also intrinsically tolerant to many antibiotics, and adaptation to host pressures enhances tolerance to first-line TB drugs. Therefore, TB antibiotic therapy takes 6 to 9 months, and current treatment regimens involve a combination of several antibiotics. Patient noncompliance due to therapeutic side effects as well as insufficient penetration of drugs into TB lesions are reasons for treatment failure and can lead to the rise of drug-resistant populations. In view of the global spread of drug-resistant strains, new antibiotics and treatment strategies are urgently needed. In this thesis, we studied the interplay of the primary host cell of Mtb, human macrophages, and different Mtb phenotypes. A low-burden infection resulted in restriction of Mtb replication via phagolysosomal effectors and the maintenance of an inactive Mtb phenotype reminiscent of dormant bacteria. Macrophages remained viable for up to 14 days, and profiling of secreted cytokines mirrored a silent infection. On the contrary, higher bacterial numbers inside macrophages could not be controlled by phagolysosomal functions, and intracellular Mtb shifted their phenotype towards active replication. Although slowed mycobacterial replication is believed to render Mtb tolerant to antibiotics, we did not observe such an effect. Mtb-induced macrophage cell death is dependent on ESAT6, a small mycobacterial virulence factor involved in host cell necrosis and the spread of the pathogen. Although well-studied, the fate of ESAT6 inside infected macrophages has been enigmatic. Cultivation of Mtb is commonly carried out in broth containing detergent to avoid aggregation of bacilli due to their waxy cell wall. Altering cultivation conditions revealed the presence of a mycobacterial capsule, and ESAT6 situated on the mycobacterial surface. Infection of macrophages with this encapsulated Mtb phenotype resulted in rapid ESAT6-dependent host cell death, and ESAT6 staining was lost as bacilli were ingested by macrophages. These observations could reflect the earlier reported integration of ESAT6 into membranes followed by membrane rupture and host cell death. In conclusion, the work presented in this thesis shows that the phenotype of Mtb has a significant impact on the struggle between the pathogen and human macrophages. Taking the bacterial phenotype into account can lead to the development of drugs active against altered bacterial populations that are not targeted by conventional antibiotics. Furthermore, deeper knowledge on Mtb virulence factors can inform the development of virulence blockers, a new class of antibiotics with great therapeutic potential.
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Bringel, Jose Magno Martins. "Caracterização bioquímica, patogênica e molecular de isolados de Ralstonia solanacearum biovar 2 de batata e berinjela." Universidade de São Paulo, 2002. http://www.teses.usp.br/teses/disponiveis/11/11135/tde-09012003-081030/.
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A murcha bacteriana, causada por Ralstonia solanacearum, afeta principalmente as solanáceas, destacando-se as culturas da batata, berinjela, jiló, pimentão e tomate. No presente trabalho foi conduzida a caracterização molecular de isolados de R. solanacearum e sua possível relação com características relacionadas à morfologia, bioquímica, patogenicidade, agressividade e distribuição geográfica. Foram utilizados 51 isolados pertencentes à biovar 2, sendo 9 provenientes de berinjela e 42 de batata, coletados em diversas regiões brasileiras. A análise molecular permitiu separar os isolados em quatro grupos distintos de padrões de bandas para os iniciadores BOX e ERIC, e em cinco para o iniciador REP. Não foi encontrada relação dos grupos de isolados caracterizados molecularmente com tamanho de colônias, ocorrência de mutantes, produção de melanina, capacidade de colonização do sistema radicular e resistência a antibióticos/fungicidas. A identificação de isolados de batata, como biovar 2-A, e de berinjela, como biovar 2-T, com base em teste bioquímico do uso de trealose, foi confirmadas pela análise molecular. Não houve variação de agressividade entre os isolados inoculados em batata e berinjela, exceção feita ao isolado avirulento CNPH-65. Portanto, isolados das biovares 2-A e 2-T podem infectar estas duas hospedeiras com a mesma intensidade sob altas temperaturas. Para todos os isolados, o desenvolvimento da população bacteriana foi significativamente maior no sistema radicular de plantas das cultivares suscetíveis, tanto para batata como para berinjela. No entanto, dentro de cada cultivar, os isolados se comportaram de maneira semelhante, não sendo possível fazer distinção entre os mesmos. A tentativa de se associar grupos de isolados caracterizados molecularmente com os locais de origem revelou alguns aspectos interessantes. O grupo I agregou somente isolados do Paraná. No grupo II ficaram isolados da Bahia, Distrito Federal e do Paraná. No Grupo III, foram reunidos todos os isolados de berinjela e um único de batata, sendo todos procedentes do Distrito Federal. O grupo IV, de forma semelhante ao grupo II, reuniu isolados de locais diversos como Paraná, Goiás, Rio Grande do Sul e Distrito Federal. Portanto, nos grupos I e III parece haver uma tendência de relação entre grupamento molecular e local de origem, enquanto que para os grupos II e IV, isolados de características genéticas similares são provenientes de locais distintos, apontando considerável diversidade genética do patógeno.The bacterial wilt disease caused by Ralstonia solonacearum affects mainly the solanaceous species, specially potato, eggplant, peppers, tomato and brazilian gilo (Solanum gilo). This work reports the molecular characterization of R. solanacearum biovar 2 isolates and the possible relationship of this molecular data with other characteristics related to morphology, biochemistry, pathogenicity, aggressiveness and geographical distribution. Fifty-one biovar 2 isolates were studied, 9 isolated from eggplant and 42 from potato, all of them collected from different regions of Brazil. According to the molecular analysis, the isolates were clustered in four different groups, with distinct band patterns to the primers BOX and ERIC, and five groups to the primers REP. There was no relationship between the groups clustered through molecular analyses and phenotypic characteristics, such as colony size, presence of mutants, melanin presence, capability of root system colonization and antibiotic/fungicide resistance. The identification of potato isolates as the biovar 2-A, and the eggplant isolates as biovar 2-T, based on biochemical tests using trealose were confirmed with the molecular analyses. There was no variation of aggressiveness in the isolates inoculated on potato an eggplant, except the avirulent isolate CNPH-65. Consequently, isolates of biovars 2-A and 2-T are able to infect both hosts with the same aggressiveness under high temperatures. The population of all isolates developed in significant levels at the root system of susceptible cultivars of both hosts, potato and eggplant. However, considering each cultivar tested, there was no difference between isolates. Interesting results were observed when the isolates clustered based on molecular data were associated with the geographical region of their collection. The group I clustered only the isolates collected in Paraná. The group II clustered the isolates collected in Bahia, Federal District and some in Paraná. The group III clustered all isolates from eggplant and only one of potato, all of them collected in the Federal District. The group IV, as the group II, clustered isolates from different regions, like Paraná, Goiás, Rio Grande do Sul and Federal District. These results suggest a relationship between the isolates clustered through molecular analysis in the groups II and III and their geographical region of collection. The isolates clustered in the same way, with similar genetic background in the groups II and IV, were however collected in different regions, showing the great genetic variation of this pathogen.
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Su, Bin. "Interaction between gastric pathogen Helicobacter pylori and host cells /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3423-1/.
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Bush, Victoria Louise. "The interaction of Neisseria meningitidis with host cells." Thesis, University of Nottingham, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361473.
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Adams, Diane. "Host plant effects on an aphid-bacterial symbiosis." Thesis, University of York, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337152.
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Haggar, Axana. "Interaction between Extracellular adherence protein (Eap) from Staphylococcus aureus and the human host." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-496-1/.
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Harden, Mark Michael Jr. "Interactions between an integrative and conjugative element and its bacterial host." Thesis, Massachusetts Institute of Technology, 2021. https://hdl.handle.net/1721.1/130662.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, February, 2021Cataloged from the official PDF of thesis.
Includes bibliographical references.
Conjugative elements are mobile genetic elements that can transfer from a donor bacterium to a recipient via an element-encoded type IV secretion system. Integrative and conjugative elements (ICEs) are an abundant class of conjugative element. ICEs are typically integrated into the bacterial host chromosome, but under certain conditions, or stochastically, they can excise from the chromosome and transfer to a recipient. ICEs likely interact with their bacterial host at every stage of their life cycle, but few of these interactions have been characterized. In this work I sought to 1) identify bacterial host factors necessary for efficient transfer of the integrative and conjugative element ICEBs1 to a recipient, and 2) determine whether the ICEBs1-encoded cell wall-modifying enzyme CwlT acts on the cell wall of the donor bacterium, the recipient bacterium, or both.
I used CRISPR interference to induce a knockdown of individual essential Bacillus subtilis genes, and then screened for gene knockdowns that caused an acute defect in transfer of ICEBs1. I found that wall teichoic acids were necessary in both ICEBs1 donors and recipients for efficient conjugative transfer. I found that depletion of wall teichoic acids caused cells involved in ICEBs1 conjugation to sustain lethal envelope damage caused by active conjugation machinery. Conjugative elements must bypass the cell wall of both the donor and recipient cells in a mating pair. Conjugative elements encode cell wall hydrolases that are required for efficient transfer, which are presumed to partly degrade the cell wall of the donor bacterium during conjugation. In order to investigate the role of the ICEBs1-encoded cell wall hydrolase CwlT in conjugation, I generated cell wall-less (L-form) strains of B. subtilis which could donate or receive ICEBs1.
In the absence of either the donor or recipient cell wall, CwlT was dispensable for efficient transfer. This finding indicates that CwlT acts on both the donor and recipient cell wall in a mating pair.
by Mark Michael Harden, Jr.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Biology
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Tsai, Yu-Huan. "Investigating human neurolisteriosis with relevant host and bacterial partners." Paris 7, 2014. http://www.theses.fr/2014PA077232.
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Listeria mononocytogenes (Lm) est une bactérie pathogène qui traverse la barrière intestinale grâce à l'interaction entre sa protéine de surface InIA et la E-cadhérine (Ecad), pour disséminer dans l'hôte et induire la listériose. Lm peut également traverser la barrière hérnato-encéphalique et induire une neurolistériose, par un mécanisme encore inconnu. L'interaction InIA-Ecad est spécifique d'espèce, InIA ne reconnait pas la Ecad de souris mais interagit avec la Ecad humaine ainsi que la Ecad humanisée exprimée par des souris génétiquement modifiées générées au laboratoire. InlA a également été "murinisée" (InlAm) afin d'interagir avec la Ecad de souris. Nous avons montré qu'InlAm reconnait non seulement la Ecad murine, mais également, contrairement à In1A, la N-cadhérine (Ncad). Cette interaction InlAm-Ncad artéfactuelle induit la translocation de la bactérie à travers les cellules M villositaires, et s'accompagne d'une inflammation intestinale et de lésions de la barrière intestinale qui ne sont pas observées chez l'homme et les souris exprimant une Ecad humanisée. Nous avons utilisé le modèle de souris humanisées pour étudier la neurolistériose. Dans ce modèle, nous avons montré que les souches cliniques issus des complexes clonaux les plus associés aux cas de neurolistériose humaine sont plus virulents et induisent plus efficacement une neurolistériose que les souches d'autres complexes clonaux et que les souches de référence, non représentatives des souches cliniques. Grâce à l'utilisation combinée des souris humanisées et des souches cliniques appropriées, nous pouvons aujourd'hui étudier la pathogenèse de la neurolistériose après infection par voie orale et déterminer les mécanismes sous-jacentsListeria monocytogenes (Lm) is a bacterial foodbome pathogen that crosses the intestinal barrier via the interaction of its surface protein InIA with its receptor E-cadherin (Ecad), and disseminate within the host to induce listeriosis. Lm can cross the placental barrier in pregnant women resulting in abortion and fetal infection, and cross the blood-CNS barrier to cause neurolisteriosis via a so far unknown mechanism. InIA-Ecad interaction is species-specific, does not occur in wild-type (wt) mice, but does in humanized mice expressing humanized mouse Ecad. InIA has also been "murinized" (InlAm) to interact with mouse Ecad in wt mice. We have shown that InlAm not only interacts with mouse Ecad, but also uses N-cadherin (Ncad) as a receptor, whereas InIA does not. This unanticipated and artifactual InlAm-Ncad interaction promotes bacterial translocation across villous M cells, accompanying with intestinal inflammation and intestinal barrier damage, ail of which are not seen in humans and humanized mouse models permissive to In1A-Ecad interaction. The widely used reference strains are not representative of clinical isolates, based on MLST, a sequence-based typing method. We have shown in a humanized mouse model of listeriosis developed in the laboratory, that the isolates originating from the most prevalent clones responsible for human neurolisteriosis are more virulent and induce far more efficiently neurolisteriosis than isolates from other clonai complexes and reference strains. By use of the humanized mouse model and relevant human CNS isolates, we are investigating the pathogenesis of orally acquired neurolisteriosis, and deciphering the underlying mechanisms of neurolisteriosis
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Matthews, Chad Robert. "Host Bacterial Interactions During Early Plaque Formation in Current and Never Smokers." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1274112198.
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Turse, Joshua Edward. "Concerning Brucella LPS: genetic analysis and role in host- agent interaction." Texas A&M University, 2005. http://hdl.handle.net/1969.1/4442.
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B rucella lipopolysaccharide is an important component of virulence in
brucellosis. Recent research in macrophage models has shown that Brucella
LPS does not behave like classical LPS by stimulating potent inflammatory
responses. The central hypothesis of this work is that O-antigen is dynamic
signaling molecular and participates in complex interactions with the host to
promote productive infection. A corollary to this is that the host environment is
dynamic, and Brucella has evolved mechanisms to cope with changing
environments. In an effort to understand the contribution of Brucella LPS to
virulence and pathogenesis, the function of a metabolic locus important in the
synthesis of LPS has been demonstrated and complemented. The spontaneous
loss of LPS expression has been characterized. Contribution of LPS to
acquisition of the host environment in tissue culture and mouse models has
been explored. This work demonstrated that genes outside the O-antigen
biosynthesis ( manBA) cluster contribute to LPS biosynthesis. Further high frequency mutation involving manBA is partly responsible for observed
dissociation of Brucella strains. Finally, work herein attempts to look at the role
of LPS in acquisition of the host environment and shows that LPS is important
for recruiting particular cell populations within a host model of brucellosis.
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White, Corin Vashoun. "The interaction between Caenorhabditis elegans and the bacterial pathogen Stenotrophomonas maltophilia." Diss., Kansas State University, 2015. http://hdl.handle.net/2097/20386.
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Doctor of PhilosophyBiology
Michael A. Herman
Nematodes play an important role in various habitats where numerous factors serve to shape their communities. One such factor is the potentially pathogenic nematode-prey interaction. This project is focused on the elucidation of the genes that the bacterivorous nematode Caenorhabditis elegans employs to respond to the emerging nosocomial bacterial pathogen Stenotrophomonas maltophilia. A virulent S. maltophilia strain JCMS requires the action of several C. elegans conserved innate immune pathways that serve to protect the nematode from other pathogenic bacteria. However, insulin-like DAF-2/16 signaling pathway mutants that are typically pathogen resistant are susceptible to JCMS, and several DAF-2/16 regulated genes are not significantly differentially expressed between JCMS and avirulent E. coli OP50. We have determined the complete set of mRNA transcripts under different bacterial treatments to identify genes that might explain this JCMS specific DAF-2/16 pathway evasion. The identified set included 438 differentially expressed transcripts among pairwise comparisons of wild-type nematodes fed OP50, JCMS or avirulent S. maltophilia K279a. Candidate genes were nominated from this list of differentially expressed genes using a probabilistic functional connection model. Six of seven genes that were highly connected within a gene network generated from this model showed a significant effect on nematode survival by mutation. Of these genes, C48B4.1, mpk-2, cpr-4, clec-67 and lys-6 are needed for combating JCMS, while dod-22 was solely involved in K279a response. Only dod-22 had a documented role in innate immunity, which merits our approach in the identification of gene candidates. To a lesser extent, we have also focused on the identification of virulence factors and the mode of action employed by S. maltophilia. JCMS virulence requires rpfF, xps and involves living bacteria that accumulate in the intestinal lumen. Additionally, the bacterial secretion encoding genes cs, p773, p1176, pi1y1 and xdi are involved in JCMS evasion of daf-2. In summary, we have discovered a novel host-pathogen interaction between C. elegans and S. maltophilia JCMS, revealed genes that are involved in each partner of the interaction, and established a new animal model for the study of S. maltophilia mode of action.
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Tujulin, Eva. "Host interactions of the intracellular bacterium Coxiella burnetii : internalisation, induction of bacterial proteins and host response upon infection /." Uppsala : Swedish Univ. of Agricultural Sciences (Sveriges lantbruksuniv.), 1999. http://epsilon.slu.se/avh/1999/91-576-5425-5.pdf.
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Moman, Raja. "Interactions of oral bacteria with host tissues and allochthonous microorganisms." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/interactions-of-oral-bacteria-with-host-tissues-and-allochthonous-microorganisms(4ddfd193-ba44-4062-8603-2082f2269273).html.
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THE UNIVERSITY OF MANCHESTER ABSTRACT OF THESIS submitted by Raja Moftah Moman for the Degree of Doctor of Philosophy entitled Interactions of Oral Bacteria with Host Tissues and Allochthonous Microorganism. 15th June 2017. The oral microbiome is a taxonomically diverse microbial community situated principally upon the hard and soft tissue surfaces of the mouth. It represents a readily accessible biofilm community for the investigation of bacteria-bacteria and bacteria-host interactions, which are responsible for some of the main features of oral biofilms in health and disease (colonisation resistance, antimicrobial tolerance, metabolic cross feeding, and other cooperative phenomena). In the oral cavity these relate specifically to cariogenesis and interactions with soft tissue that are responsible for periodontal disease. This doctoral thesis presents a series of investigations that consider processes for which growth in the biofilm phenotype or bacterial-bacteria or bacteria-host cell interaction are responsible. Four distinct methods were used to assess the effect of the biofilm phenotype on susceptibility of eight distinct oral hygiene actives with various modes of action. Bisphenol microbicide triclosan and the bis-biguanide chlorhexidine were most effective. All were markedly more effective against bacteria grown planktonically than the same organisms grown as biofilms illustrating antimicrobial tolerance, an important biofilm characteristic. In studies of interactions between oral isolates, bacteria previously isolated from the saliva and different oral sites of the oral cavity were tested using a modified cross streak method, in all possible pair-wise combinations. The frequency and strength of physical interactions (coaggregation) between these isolates was also assessed. The incidence of positive interactions was higher than the incidence of negative interactions (15.21% vs. 1.04%) and the incidence of coaggregation in bacteria isolated from saliva was significantly lower than for bacteria isolated from oral biofilms. Together, these data suggest that bacterial cooperation plays a greater role in oral biofilm development and maintenance than competition. With respect to putatively beneficial interactions between bacteria and host, the potential of the candidate dental probiotics L. rhamnosus GG, L. reuteri and S. salivarius to protect host tissues from damage by three Gram negative periodontal pathogens were investigated using human oral cells culture and the (invertebrate) G. mellonella model system. All probiotics inhibited the growth of the test pathogens when applied simultaneously, and significantly decreased toxicity (p P. gingivalis > A. actinomycetemcomitans) in two distinct cell lines. Whilst all probiotics conferred protection against the periodontal pathogens, L. rhamnosus GG, had the greatest protective effect, regardless of probiotic or pathogen used, followed by L. reuteri. S. salivarius was the least effective. Prophylactic treatment with probiotics conferred greater protection than treatment concomitant with pathogen challenge. The data presented in this doctoral thesis demonstrate the functional significance of interactions between taxonomically distinct bacteria and between bacteria and host tissues. Such interactions may determine the outcome of exposure to antimicrobials and are, particularly significant in health and through further research, may be harnessed for prevention and treatment of oral disease.
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Suri, Reetika. "The effect of welding fumes and smoking on host-pathogen interactions in bacterial pneumonia." Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/9100.
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Background: Epidemiological evidence supports a strong association between exposure to inhaled toxins and adverse respiratory outcomes such as pneumococcal pneumonia and chronic respiratory conditions such as chronic obstructive pulmonary disorder (COPD). Chronic exposure to airborne particulate matter in occupational settings, such as welding, has been shown to reversibly increase risk of pneumococcal pneumonia. However, biological plausibility of this has not been shown and the molecular mechanisms are unknown. Chronic cigarette smoking causes reduced lung function and increased morbidity in COPD patients. These patients are highly vulnerable to viral and secondary pneumococcal infections. The molecular mechanisms are unclear. Methods: Association between exposure to welding fumes (WF) and susceptibility to pneumococcal infection, rhinoviral infection and rhinoviral+secondary pneumococcal infection was assessed in lower airway and nasal epithelial cells in vitro. The role of the platelet activating factor receptor (PAFR), which is an entry receptor for the pneumococcus, was also assessed. Using two methods of WF exposure, susceptibility to pneumococcal infection following acute and chronic exposure was assessed in mice. Finally, PAFR expression was examined in the lungs of non-smokers, welders, smokers and smokers with COPD. Results: Exposure of alveolar, bronchial and nasal epithelial cells to WF significantly increases pneumococcal invasion of these cells in a PAFR dependent manner. Exposure to WF increases susceptibility to infection by rhinovirus and vulnerability to secondary pneumococcal infections in a PAFR dependent manner. Exposure to WF increases susceptibility of mice to pneumococcal infection and PAFR mRNA expression levels in the lungs. Finally, PAFR mRNA levels are elevated in smokers with COPD compared with non-smokers. PAFR protein expression in the lungs of smokers with COPD is localised to the bronchial epithelium and bronchial glands. 4 Conclusions: PAFR is a potential anti-infective agent in pneumococcal pneumonia caused by exposure to WF and in COPD caused by chronic exposure to smoking.
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Vaitkevičius, Karolis. "Effects of Vibrio cholerae protease and pigment production on environmental survival and host interaction /." Umeå : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1474.
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Hutchinson, J. L. "Intracellular targeting mechanisms of Salmonella virulence effector proteins, and bacterial interactions with host antigen presentation pathways." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604849.
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SPI2 effectors are responsible for an observed Salmonella-specified downregulation of MHC Class II at the surface of infected cells. The cooperative contribution of SPI2 effector interactions to the maturation of the Salmonella-containing vacuole (SCV) leads to the hypothesis that correct localisation of effectors following their secretion into the host cell is important to their function. Work described herein characterises the localisation of a key virulence factor, SifA, which contains a cysteine-rich C-terminal motif previously proposed to be a site for host lipid attachment. A role was demonstrated for lipid modification in retention of SifA at the SCV following secretion. However, membrane association and initial localisation of SifA to the SCV was shown to be independent of C-terminal lipid attachment, and instead likely dependent on the protein N terminus which shares homology with a subset of SPI2 effector N termini previously implicated in intracellular targeting. This thesis also characterises the distribution of host antigen presenting molecules within infected cells, drawing comparison between MHC Class II and the four surface isoforms of the non-classical lipid antigen-presenting CD1 molecules. Salmonella was shown to traffic through CD1-positive compartments yet in contrast to MHC Class II none of the CD1 isoforms were downregulated at the surface of infected MelJuso cells.
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Vries, Frederik Peter de. "Colonization and invasion of human epithelia by Neisseria meningitidis bacterial surface variation and exploitation of host defense molecules /." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2001. http://dare.uva.nl/document/58434.
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Olive, Andrew James. "Immunity to Chlamydia trachomatis and Host-Pathogen Interactions During Infection." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11263.
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Infections with the bacterial pathogen Chlamydia trachomatis are a critical public health problem. Chlamydia remains the number one cause of preventable blindness worldwide and the leading cause of bacterial sexually transmitted infections in the United States. In humans, repeat and persistent infections with Chlamydia result in severe inflammation. Inflammation in the conjunctiva can result in blindness, while inflammation in the genital tract can result in pelvic inflammatory disease, ectopic pregnancy or infertility. In order to curb the increasing incidence of Chlamydia infections worldwide it will be necessary to develop a protective vaccine that affords long-term protection and prevents pathologies. To better inform vaccine development we must understand the mechanisms that drive long-term immunity in the genital tract and elucidate critical interactions between Chlamydia and host cells to uncover potential mechanisms of immune evasion.
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Boardman, Cynthia. "Host-Pathogen Interactions between Eastern Oysters (Crassostrea virginica) and the Bacterial Agent of Juvenile Oyster Disease (Roseovarius crassostreae)." Fogler Library, University of Maine, 2005. http://www.library.umaine.edu/theses/pdf/BoardmanC2005.pdf.
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Björkqvist, Maria. "Coagulase-negative staphylococci septicaemia in newborns : aspects on host-bacterial interactions with special regard to neutrophil and endothelial response /." Linköping : Univ, 2004. http://www.bibl.liu.se/liupubl/disp/disp2004/med861s.pdf.
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Sokolova, Nadiia Verfasser], and Theresia [Akademischer Betreuer] [Stradal. "Identification and characterization of interactions between bacterial WxxxE-virulence proteins and host cell proteins / Nadiia Sokolova ; Betreuer: Theresia Stradal." Braunschweig : Technische Universität Braunschweig, 2017. http://d-nb.info/1175817961/34.
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Thay, Bernard. "Vesicle-mediated and free soluble delivery of bacterial effector proteins by oral and systemic pathogens." Doctoral thesis, Umeå universitet, Institutionen för odontologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-82782.
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Periodontitis, the primary cause of tooth-loss worldwide, is a bacterially induced chronic inflammatory disease of the periodontium. It is associated with systemic conditions such as cardiovascular disease (CVD). However, pathogenic mechanisms of periodontitis-associated bacteria that may contribute to the CVD association are unclear. The aim of this doctoral thesis project was to characterize bacterial mechanisms that can originate from the periodontal pocket and expose the host to multiple effector proteins, thereby potentially contributing to periodontal tissue degradation and systemic stimulation. As our main model, we have used Aggregatibacter actinomycetemcomitans, a Gram-negative species associated with aggressive forms of periodontitis, and with non-oral infections, such as endocarditis. Since Gram-positive species might be more common in periodontitis than previously believed, we have also investigated mechanisms of the multipotent bacterium, Staphylococcus aureus. Using an ex vivo insert model we showed that free-soluble surface material, released during growth by A. actinomycetemcomitans independently of outer membrane vesicles (OMVs), enhanced the expression of several proinflammatory cytokines in human whole blood. A clear LPS-independent effect suggested the involvement of effector proteins in this cytokine stimulation. This was supported by MALDI-TOF-MS and immunoblotting, which confirmed the release of GroEL and peptidoglycan-associated lipoprotein (PAL), in free-soluble form. We next demonstrated that A. actinomycetemcomitans OMVs could deliver multiple proteins including biologically active cytolethal distending toxin (CDT), a major virulence factor, into human gingival fibroblasts and HeLa cells. Using confocal microscopy, the active toxin unit, CdtB, was localized inside the nucleus of the intoxicated cells, whereas OmpA and proteins detected using an antibody specific to whole A. actinomycetemcomitans serotype a cells had a perinuclear distribution. By using a fluorescent probe, B-R18, it was shown that the OMVs fused with lipid rafts in the plasma membrane. These findings suggest that OMVs can deliver biologically active virulence factors such as CDT into susceptible cells of the periodontium. Using A. actinomycetemcomitans vesicles labeled with the lipophilic dye, PKH26, it was shown that the OMVs can be internalized into the perinuclear region of human cells in a cholesterol-dependent manner. Co-localization analysis supported that the internalized OMVs carried A. actinomycetemcomitans antigens. Inhibition assays suggested that although OMV internalization appeared to have a major role in effector protein delivery, additional interactions such as vesicle membrane fusion may also contribute. The OMVs strongly induced activation of the cytosolic pathogen recognition receptors NOD1 and NOD2 in HEK293T-cells, consistent with a role in triggering innate immunity by carrying PAMPs such as peptidoglycan into host cells. Membrane vesicles (MVs) from S. aureus were found to carry biologically active alpha-toxin, a key virulence factor, which was delivered to host cells and required for full cytotoxicity of the vesicles. Confocal microscopy analysis revealed that these MVs, similar to A. actinomycetemcomitans OMVs, interacted with HeLa cells via membrane fusion. Thus, as S. aureus is frequently found in individuals with aggressive periodontitis, MV production could have potential to contribute to the severity of tissue destruction.
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Langer, Melissa Natalie [Verfasser]. "Interactions of host defence peptides with innate immune cells : unravelling molecular mechanisms of immune modulation and bacterial killing / Melissa Natalie Langer." Hannover : Stiftung Tierärztliche Hochschule Hannover, 2018. http://d-nb.info/118040288X/34.
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Jehl, Marc-André [Verfasser], Dmitrij [Akademischer Betreuer] [Gutachter] Frischmann, and Thomas [Gutachter] Rattei. "Computational methods for the prediction of bacterial pathogen-host protein protein interactions / Marc-André Jehl. Betreuer: Dmitrij Frischmann. Gutachter: Thomas Rattei ; Dmitrij Frischmann." München : Universitätsbibliothek der TU München, 2016. http://d-nb.info/1100689001/34.
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Bhullar, Kirandeep. "Mucus-bacteria interactions in the gut : investigating the role of the mucin Muc2 and its glycosylation in host defense during enteric bacterial infections." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/57682.
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The intestinal mucus layer, which is largely composed of the secreted mucin Muc2 provides a first line of defense in the intestine. Muc2 is a heavily O-glycosylated protein with core 1 and core 3 derived O-glycans as primary constituents. It plays an important role in host defense against the attaching/effacing (A/E) pathogen Citrobacter rodentium. However whether it provides protection against the invasive human pathogen Salmonella is still unclear. Furthermore, the role of O-glycosylation in mediating the protective role played by the Muc2 mucin against enteric pathogens has not been investigated. Likewise, although almost all enteric bacterial pathogens must cross the overlying mucus layer to infect the intestinal epithelium, there is very little known about mucus-enteric bacterial interactions and virulence strategies used to accomplish this feat. We began our investigations by comparing Salmonella-induced colitis and mucus dynamics in Muc2-deficient (Muc2 -/-), C3GnT -/-, and C57BL/6 (WT) mice. While absence of core 3 derived O-glycosylation only impacted epithelial barrier integrity, absence of Muc2 resulted in significantly higher barrier disruption, host mortality rates, and increased colonic and systemic Salmonella burdens. Likewise, absence of core 1 derived O-glycans (C1galt1 -/- mice) resulted in heightened susceptibility to C. rodentium, characterized by impaired mucus levels in the lumen, and bacterial aggregation in close proximity to the intestinal epithelial surface, phenotypes not seen in WT or C3GnT -/- counterparts. To understand if the non-motile pathogen C. rodentium used bacterial proteases/mucinases as a mucus degrading strategy to gain access to the underlying epithelium, we investigated the role of a putative mucinase and a class 2 SPATE PicC. While PicC did not affect C. rodentium’s ability to colonize the colon, it appeared to have an unprecedented role in regulating C. rodentium’s activation of the innate receptor TLR2, suggesting that despite its mucinase activity, PicC's major roles in vivo may be to limit C. rodentium aggregation and its recognition by the host's innate immune system. Overall these studies highlight a novel protective role of Muc2 and its O-linked glycosylation in host defense against enteric infections and the importance of Muc2-mediated regulation of pathogen burdens at the intestinal epithelial surface.Medicine, Faculty of
Medicine, Department of
Experimental Medicine, Division of
Graduate
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Ripert, Gabrielle. "Etude du mode d’action des souches Bacillus subtilis CU1 et Bacillus clausii O/C, probiotiques humains, et de leurs interactions avec l'hôte via des modèles in vitro et in vivo." Thesis, Paris, AgroParisTech, 2013. http://www.theses.fr/2013AGPT0019.
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Les probiotiques sont des « microorganismes vivants qui, lorsqu’ils sont ingérés en quantité suffisante, exercent un effet positif sur la santé de l’hôte ». Ils agissent en modulant le système immunitaire, en empêchant l’adhésion et/ou la croissance des bactéries pathogènes, en renforçant la barrière intestinale et en stabilisant sa microflore. Cependant, les mécanismes d’action de ces bactéries restent encore peu connus.Ce travail de thèse propose d’élucider les modes d’action de deux souches de Bacillus probiotiques humains : Bacillus clausii O/C et de Bacillus subtilis CU1.L’adhésion des probiotiques aux surfaces intestinales est un facteur important pour leur persistance dans l’organisme, l’immunomodulation et la compétition envers les agents pathogènes. B. clausii et B. subtilis présentent de fortes capacités d’adhésion sous forme de spores grâce à leurs protéines de surface préférentiellement impliquées dans les interactions avec l’hôte. En effet, celles-ci jouent un rôle prépondérant dans la stimulation de l’expression des gènes codant les cytokines dans les cellules Caco-2 et la production de cytokines par les cellules immunitaires, induite par les souches probiotiques, via la liaison avec des récepteurs de l’hôte. Des protéines S-layers, protéines ribosomales et protéases ont été identifiées à la surface de ces souches, ainsi qu’une grande quantité de flagelline à la surface de B. subtilis.Par ailleurs, les composés sécrétés par les souches stimulent également la production de cytokines chimiotactiques et anti-inflammatoires. B. clausii sécrète une protéase capable de neutraliser plusieurs types de toxines dont celles sécrétées par C. difficile et B. cereus. B. subtilis n’a montré aucune propension pour l’inhibition de l’adhésion des agents pathogènes testés, mais un essai clinique a démontré sa capacité à moduler le système immunitaire et la composition du microbiote intestinalProbiotic are ”live microorganisms, which when administered in adequate amounts confer a health benefit on the host”. They act by modulating the immune system, preventing the adhesion and / or growth of pathogenic bacteria, reinforcing the intestinal barrier and stabilizing the microbiota.However, the mechanisms of action of these bacteria are still poorly understood.This thesis proposes to elucidate the mode of action of two human probiotic strains of Bacillus : Bacillus clausii O / C and Bacillus subtilis CU1.The adhesion of probiotics to intestinal surfaces is an important factor for their persistence in the host, immunomodulation and competition with pathogens. B. clausii and B. subtilis have strong abilities to adhere as spores, through their surface-associated proteins which are preferentially involved in interactions with the host. Indeed, they play a key role in the up-regulation of gene expression encoding cytokines in Caco-2 cells and in the stimulation of cytokine production by immune cells, induced by probiotic strains, through binding with host receptors. Some S-layers proteins, ribosomal proteins and proteases have been identified on the surface of these strains, and a large quantity of flagellin on the surface of B. subtilis.In addition, secreted compounds of these probiotics also stimulate the production of chemotactic and anti-inflammatory cytokines. B. clausii secretes a protease able to neutralize several types of toxins, including those secreted by C. difficile and B. cereus. B. subtilis has not predisposition to compete with the adhesion of pathogens tested, but a clinical trial has demonstrated its ability to modulate the immune system and the composition of the intestinal microbiota
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Schrallhammer, Martina, Filippo Ferrantini, Claudia Vannini, Stefano Galati, Michael Schweikert, Hans-Dieter Görtz, Franco Verni, and Giulio Petroni. "'Candidatus Megaira polyxenophila' gen. nov., sp. nov.: Considerations on Evolutionary History, Host Range and Shift of Early Divergent Rickettsiae." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-127288.
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“Neglected Rickettsiaceae” (i.e. those harboured by non-hematophagous eukaryotic hosts) display greater phylogenetic variability and more widespread dispersal than pathogenic ones; yet, the knowledge about their actual host range and host shift mechanism is scarce. The present work reports the characterization following the full-cycle rRNA approach (SSU rRNA sequence, specific in situ hybridization, and ultrastructure) of a novel rickettsial bacterium, herewith proposed as 'Candidatus Megaira polyxenophila' gen. nov., sp. nov. We found it in association with four different free-living ciliates (Diophrys oligothrix, Euplotes octocarinatus, Paramecium caudatum, and Spirostomum sp., all belonging to Alveolata, Ciliophora); furthermore it was recently observed as intracellular occurring in Carteria cerasiformis and Pleodorina japonica (Chlorophyceae, Chlorophyta). Phylogenetic analyses demonstrated the belonging of the candidate new genus to the family Rickettsiaceae (Alphaproteobacteria, Rickettsiales) as a sister group of the genus Rickettsia. In situ observations revealed the ability of the candidate new species to colonize either nuclear or cytoplasmic compartments, depending on the host organism. The presence of the same bacterial species within different, evolutionary distant, hosts indicates that 'Candidatus Megaira polyxenophila' recently underwent several distinct host shifts, thus suggesting the existence of horizontal transmission pathways. We consider these findings as indicative of an unexpected spread of rickettsial infections in aquatic communities, possibly by means of trophic interactions, and hence propose a new interpretation of the origin and phylogenetic diversification of rickettsial bacteria.
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Baudry, Lyam. "Investigating chromosome dynamics through Hi-C assembly." Electronic Thesis or Diss., Sorbonne université, 2019. http://www.theses.fr/2019SORUS026.
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L'avènement des technologies de séquençage ADN à haut-debit a initié une tendance grandissante dans l'assemblage de génomes. La qualité de ces génomes est un prérequis essentiel pour comprendre les interactions au sein de et entre ces chromosomes. Nos méthodes se basent principalement sur les technologies de capture de conformation de chromosomes comme le Hi-C. Lors d'un protocole de Hi-C, les molécules d'ADN sont réticulées avec les protéines environnantes pour former un complexe protéine-ADN statique et volumineux. Ceci permet de capturer la conformation spatiale en piégeant les molécules physiquement proches dans l'espace. Ainsi, le Hi-C est très approprié pour l'analyse de la structure 3D des génomes, ce qui permet d'obtenir un certain nombre d'informations sur le génome. Il a été ainsi montré que sa structure tridimensionnelle peut être reliée directement à sa structure 1D grâce aux propriétés physiques des polymères d'ADN. De plus, une telle proximité en 3D donne également accès à des informations de compartimentation, ce qui a ouvert la voie à une nouvelle approche de binning métagénomique, connue sous le nom de meta3C. Au cours de ce travail, nous étendons ces méthodes à des études de cas présentant une complexité grandissante. Tout d'abord, nous améliorons les outils d'assemblage de génomes et démontrons leur validité avec l'assemblage de Ectocarpus sp., puis nous mettons en évidence des réarrangements chromosomiques au sein d'assemblages joints de Trichoderma reesei et Cataglyphis hispanica. Enfin, nous utilisons la même approche avec le binning métagénomique sur des échantillons de souris in vivo afin de reconstruire des centaines de génomesThe advent of high-throughput DNA sequencing technologies has set off an expanding trend in genome assembling and scaffolding. Such genome quality is an essential preliminary to understand interactions between and among chromosomes. We built upon a computational and technological framework that let us tackle genome assembly problems of increasing complexity. Our methods are mainly based on chromosome conformation capture technologies such as Hi-C. In a Hi-C experiment, DNA molecules are cross-linked with the surrounding proteins and form a large, static protein-DNA complex. This captures the spatial conformation by trapping together molecules that are physically close to each other. Therefore, Hi-C is very suitable for 3D genome structure analysis, which lets us infer a wealth of information about the genome. It was indeed shown that the tridimensional structure of the genome can be unambiguously linked to its 1D structure thanks to the physical properties of DNA polymers. Moreover, such 3D proximity also gives access to cell compartment information, thus opening the way for an additional approach for metagenomic binning, known as meta3C. In this work, we expand upon these methods and apply them to use cases with more and more complexity. We first improve on tools for genome assembly and demonstrate their validity with the scaffolding of Ectocarpus sp., then unveil rearrangements in joint scaffoldings of Trichoderma reesei and Cataglyphis hispanica. Lastly, we use the same approach with metagenomic binning on live mouse microbiome samples to reconstruct hundreds of genomes
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Olofsson, Jenny. "Amoebae as Hosts and Vectors for Spread of Campylobacter jejuni." Doctoral thesis, Uppsala universitet, Institutionen för medicinska vetenskaper, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-255804.
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Campylobacter jejuni is the leading bacterial cause of gastrointestinal diarrheal disease in humans worldwide. This zoonotic pathogen has a complex epidemiology due to its presence in many different host organisms. The overall aim of this thesis was to explore the role of amoebae of the genus Acanthamoeba as an intermediate host and vector for survival and dissemination of C. jejuni. Earlier studies have shown that C. jejuni can enter, survive and replicate within Acanthamoebae spp. In this thesis, I have shown that C. jejuni actively invades Acanthamoeba polyphaga. Once inside, C. jejuni could survive within the amoebae by avoiding localization to degradative lysosomes. We also found that A. polyphaga could protect C. jejuni in acid environments with pH levels far below the range in which the bacterium normally survives. Furthermore, low pH triggered C. jejuni motility and invasion of A. polyphaga. In an applied study I found that A. polyphaga also could increase the survival of C. jejuni in milk and juice both at room temperature and at +4ºC, but not during heating to recommended pasteurization temperatures. In the last study we found that forty environmental C. jejuni isolates with low bacterial concentrations could be successfully enriched using the Acanthamoeba-Campylobacter coculture (ACC) method. Molecular genetic analysis using multilocus sequence typing (MLST) and sequencing of the flaA gene, showed no genetic changes during coculture. The results of this thesis have increased our knowledge on the mechanisms behind C. jejuni invasion and intracellular survival in amoebae of the genus Acanthamoeba. By protecting C. jejuni from acid environments, Acanthamoebae could serve as important reservoirs for C. jejuni e.g. during acid sanitation of chicken stables and possibly as vectors during passage through the stomach of host animals. Furthermore, Acanthamoeba spp. could serve as a vehicle and reservoir introducing and protecting C. jejuni in beverages such as milk and juice. Validation of the ACC method suggests that it is robust and could be used even in outbreak investigations where genetic fingerprints are compared between isolates. In conclusion, Acanthamoeba spp. are good candidates for being natural hosts and vectors of C. jejuni.
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Weng, Dan. "Caspase-8 and RIP Kinases Regulate Bacteria-Induced Innate Immune Responses and Cell Death: A Dissertation." eScholarship@UMMS, 2014. https://escholarship.umassmed.edu/gsbs_diss/727.
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Yersinia pestis (Y. pestis), as the causative agent of plague, has caused deaths estimated to more than 200 million people in three historical plague pandemics, including the infamous Black Death in medieval Europe. Although infection with Yersinia pestis can mostly be limited by antibiotics and only 2000-5000 cases are observed worldwide each year, this bacterium is still a concern for bioterrorism and recognized as a category A select agent by the Centers for Disease Control and Prevention (CDC). The investigation into the host-pathogen interactions during Y. pestis infection is important to advance and broaden our knowledge about plague pathogenesis for the development of better vaccines and treatments.
Y. pestis is an expert at evading innate immune surveillance through multiple strategies, several mediated by its type three secretion system (T3SS). It is known that the bacterium induces rapid and robust cell death in host macrophages and dendritic cells. Although the T3SS effector YopJ has been determined to be the factor inducing cytotoxicity, the specific host cellular pathways which are targeted by YopJ and responsible for cell death remain poorly defined. This thesis research has established the critical roles of caspase-8 and RIP kinases in Y. pestis-induced macrophage cell death. Y. pestis-induced cytotoxicity is completely inhibited in RIP1-/- or RIP3-/-caspase-8-/- macrophages or by specific chemical inhibitors. Strikingly, this work also indicates that macrophages deficient in either RIP1, or caspase-8 and RIP3, have significantly reduced infection-induced production of IL-1β, IL-18, TNFα and IL-6 cytokines; impaired activation of NF-κB signaling pathway and greatly compromised caspase-1 processing; all of which are critical for innate immune responses and contribute to fight against pathogen infection. Y. pestis infection causes severe and often rapid fatal disease before the development of adaptive immunity to the V bacterium, thus the innate immune responses are critical to control Y. pestis infection. Our group has previously established the important roles of key molecules of the innate immune system: TLR4, MyD88, NLRP12, NLRP3, IL-18 and IL-1β, in host responses against Y. pestis and attenuated strains. Yersinia has proven to be a good model for evaluating the innate immune responses during bacterial infection. Using this model, the role of caspase-8 and RIP3 in counteracting bacterial infection has been determined in this thesis work. Mice deficient in caspase-8 and RIP3 are very susceptible to Y. pestis infection and display reduced levels of pro-inflammatory cytokines in spleen and serum, and decreased myeloid cell death. Thus, both in vitro and in vivo results indicate that caspase-8 and RIP kinases are key regulators of macrophage cell death, NF-κB and caspase-1 activation in Yersinia infection. This thesis work defines novel roles for caspase-8 and RIP kinases as the central components in innate immune responses against Y. pestis infection, and provides further insights to the host-pathogen interaction during bacterial challenge.
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Weng, Dan. "Caspase-8 and RIP Kinases Regulate Bacteria-Induced Innate Immune Responses and Cell Death: A Dissertation." eScholarship@UMMS, 2007. http://escholarship.umassmed.edu/gsbs_diss/727.
Full textAbstract:
Yersinia pestis (Y. pestis), as the causative agent of plague, has caused deaths estimated to more than 200 million people in three historical plague pandemics, including the infamous Black Death in medieval Europe. Although infection with Yersinia pestis can mostly be limited by antibiotics and only 2000-5000 cases are observed worldwide each year, this bacterium is still a concern for bioterrorism and recognized as a category A select agent by the Centers for Disease Control and Prevention (CDC). The investigation into the host-pathogen interactions during Y. pestis infection is important to advance and broaden our knowledge about plague pathogenesis for the development of better vaccines and treatments.
Y. pestis is an expert at evading innate immune surveillance through multiple strategies, several mediated by its type three secretion system (T3SS). It is known that the bacterium induces rapid and robust cell death in host macrophages and dendritic cells. Although the T3SS effector YopJ has been determined to be the factor inducing cytotoxicity, the specific host cellular pathways which are targeted by YopJ and responsible for cell death remain poorly defined. This thesis research has established the critical roles of caspase-8 and RIP kinases in Y. pestis-induced macrophage cell death. Y. pestis-induced cytotoxicity is completely inhibited in RIP1-/- or RIP3-/-caspase-8-/- macrophages or by specific chemical inhibitors. Strikingly, this work also indicates that macrophages deficient in either RIP1, or caspase-8 and RIP3, have significantly reduced infection-induced production of IL-1β, IL-18, TNFα and IL-6 cytokines; impaired activation of NF-κB signaling pathway and greatly compromised caspase-1 processing; all of which are critical for innate immune responses and contribute to fight against pathogen infection. Y. pestis infection causes severe and often rapid fatal disease before the development of adaptive immunity to the V bacterium, thus the innate immune responses are critical to control Y. pestis infection. Our group has previously established the important roles of key molecules of the innate immune system: TLR4, MyD88, NLRP12, NLRP3, IL-18 and IL-1β, in host responses against Y. pestis and attenuated strains. Yersinia has proven to be a good model for evaluating the innate immune responses during bacterial infection. Using this model, the role of caspase-8 and RIP3 in counteracting bacterial infection has been determined in this thesis work. Mice deficient in caspase-8 and RIP3 are very susceptible to Y. pestis infection and display reduced levels of pro-inflammatory cytokines in spleen and serum, and decreased myeloid cell death. Thus, both in vitro and in vivo results indicate that caspase-8 and RIP kinases are key regulators of macrophage cell death, NF-κB and caspase-1 activation in Yersinia infection. This thesis work defines novel roles for caspase-8 and RIP kinases as the central components in innate immune responses against Y. pestis infection, and provides further insights to the host-pathogen interaction during bacterial challenge.
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Geniez, Sandrine. "Investigation of Wolbachia symbiosis in isopods and filarial nematodes by genomic and interactome studies." Thesis, Poitiers, 2013. http://www.theses.fr/2013POIT2277/document.
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Les Wolbachia sont des alpha-proteobactéries présentes chez de nombreux arthropodes et nématodes filaires. Ces bactéries héritées maternellement induisent chez leurs hôtes des phénotypes allant du parasitisme au mutualisme, avec le long de ce continuum des phénotypes tels que la féminisation (F), l'incompatibilité cytoplasmique (IC) ou la mort des mâles. Wolbachia est ainsi un modèle particulièrement intéressant pour étudier les différents types de relations symbiotiques.Chez Brugia malayi, comme pour les autres nématodes filaires, Wolbachia vit en symbiose obligatoire avec son hôte. L'élimination de la bactérie par des traitements antibiotiques entraîne une perte de fertilité voire la mort du nématode. Chez l'isopode terrestre Armadillidium vulgare, Wolbachia induit la féminisation des mâles génétiques en femelles fonctionnelles entraînant des biais de sex-ratio vers les femelles dans la descendance.Pour comprendre les mécanismes impliqués dans ces deux symbioses, nous avons mis au point une nouvelle méthode de capture pour isoler l'ADN de Wolbachia et séquencer 8 souches de Wolbachia d'isopodes (F et IC). Une étude de génomique comparative a permis d'établir un premier pan-génome des bactéries du genre Wolbachia et d'identifier 2, 5 et 3 gènes présents seulement chez les souches mutualistes, féminisantes ou induisant la mort des mâles. L'expression des gènes potentiellement impliqués dans la féminisation ou le mutualisme a été étudiée au cours du développement de l'hôte. L'étude de l'interactome protéique bactérie-hôte a ensuite été initiée en utilisant comme appât des protéines bactériennes à domaines eucaryotes en vue d'identifier les cibles de Wolbachia chez l'hôteBacteria of the genus Wolbachia are gram-negative alpha-proteobacteria present in many arthropods and filarial nematodes. These obligate intracellular bacteria are maternally inherited and induce a large number of phenotypes across the symbiosis continuum from mutualism to parasitism, including feminization (F), cytoplasmic incompatibility (CI) or male killing. Studying Wolbachia symbioses is therefore of particular interest in the investigation of symbiotic relationships.In Brugia malayi and other filarial nematodes, they are obligate leading to a loss of worm fertility, and eventual death upon their depletion with antibiotic. In arthropods, they rather are parasitic. In the isopod crustacean Armadillidium vulgare they cause feminization when present: genetic males develop as functional female leading to female biased sex-ratio progenies.In order to understand the molecular mechanisms of these two symbioses, we set up a new capture procedure to catch Wolbachia DNA and performed whole-genome sequencing on 8 Wolbachia strains, symbionts of isopods (F & CI). Comparative genomics led to the establishment of the Wolbachia pan-genome as well as the identification of phenotype related gene patterns. We identified 2, 5 and 3 genes that are only found in mutualist, feminizing and male killing strains, respectively. Expression of genes potentially involved in feminization and mutualism were also analyzed throughout host post-embryonic development. Host-symbiont interactome approach was then initiated by protein-protein interaction studies using bacterial proteins with eukaryote like motifs as bait in order to identify Wolbachia host targets involved in symbiosis
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Lam, Grace. "Interactions of L. monocytogenes with Host Cellular Defenses." Thesis, 2012. http://hdl.handle.net/1807/32799.
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Listeria monocytogenes is an intracellular bacterium that utilizes two phospholipases C (PLCs) and a pore-forming cytolysin (listeriolysin O, LLO) to escape the phagosome. However, prior to escape, the bacterium must overcome a number of phagosomal defenses, including autophagy and NOX2 NADPH oxidase production of reactive oxygen species (ROS).
Autophagy, the cellular process of self-digestion, is a key component of innate immunity. Previously, it has been shown that L. monocytogenes is targeted by autophagy (LC3+) at 1 h post infection (p.i.) but the mechanism remains elusive. Here, I show that at 1 h p.i., diacylglycerol (DAG) and ROS production are required for autophagy targeting to the bacteria, which are predominantly in phagosomes. It has been shown that autophagy targeting of cytosolic L. monocytogenes is mediated via protein ubiquitination. However, protein ubiquitination is not associated with LC3+ bacteria at 1 h p.i.. Thus, my data suggest that distinct signals mediate autophagy targeting of L. monocytogenes depending on the location within host cells.
Given that ROS mediate autophagy targeting to L. monocytogenes and that previous studies have demonstrated that ROS production limits bacterial escape, I investigated how L. monocytogenes overcomes ROS production prior to phagosomal escape. I found that LLO inhibits ROS production by preventing NOX2 NADPH oxidase localization to L. monocytogenes-containing phagosomes. LLO-deficient bacteria can be complemented by perfringolysin O, a related cytolysin, suggesting that other pathogens may also use pore-forming cytolysins to inhibit ROS production. While PLCs can activate ROS production, this effect is alleviated by LLO pore-formation. Therefore, the combined activities of PLCs and LLO allow L. monocytogenes to efficiently escape the phagosome while avoiding microbicidal ROS.
Together, this thesis provides a clearer understanding of the balance between host defense versus bacterial evasion. Greater insight into host-bacterial interaction may lead to better therapeutics that can “tip the balance” in the host’s favour.
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Venkatesh, Balakrishnan. "CHARACTERIZATION OF BACTERIAL LIPOPOLYSACCHARIDES (Pseudomonas syringae pv. tomato and Pseudomonas syringae pv. apii) AND PECTINS OF TOMATO AND CELERY PLANTS (Lycopersicon esculentum and Apium graveolens) REGARDING THEIR POSSIBLE ROLE IN HOST/PATHOGEN-INTERACTION." Doctoral thesis, 2002. http://hdl.handle.net/11858/00-1735-0000-0006-AC15-6.
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Hsieh, Shang-Chen. "Swarming regulation and bacteria-host interaction in Serratia marcescens: -A novel lipoprotein SspA regulates S. marcescens swarming -2,3-butanediol, a bacterial metabolite, ameliorates acute inflammatory response induced by LPS in rat model." 2008. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-1403200811054000.
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Hsieh, Shang-Chen, and 謝尚諶. "Swarming regulation and bacteria-host interaction in Serratia marcescens:-A novel lipoprotein SspA regulates S. marcescens swarming-2,3-butanediol, a bacterial metabolite, ameliorates acute inflammatory response induced by LPS in rat model." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/89712090934927673123.
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博士臺灣大學
醫學檢驗暨生物技術學研究所
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Swarming in Serratia marcescens is a specialized form of bacterial surface migration. S. marcescens swarms at 30 ºC but not at 37 ºC on 0.8 % LB agar plate. To unravel the underlying mechanisms of the temperature-dependent swarming behavior, transposon mutagenesis was performed to screen for mutants that swarmed at 37 ºC. SspA, a novel lipoprotein, was identified to involve the negative regulation of S. marcescens swarming at 37 ºC. Increased production of biosurfactant, over-synthesis of flagellum and the reduced biofilm formation in sspA mutant S. marcescens SC101 all might contribute to the precocious-swarming behavior of S. marcescens SC101 at 37 ºC. Furthermore, the increased hemolytic activity of precocious-swarming mutant suggested that the regulation of swarming is closely related to the pathogenesis of S. marcescens. Besides, we also asked why S. marcescens is an important nosocomial pathogen. Herein, we showed that gastric intubation of 2,3-butanediol, a pyruvate metabolite produced by S. marcescens, in rats significantly ameliorates acute lung injury and the inflammatory responses induced by S. marcescens derived endotoxin lipopolysaccharide (LPS), with an efficacy comparable to that of the polyphenol compound resveratrol. Such effect was further demonstrated to occur via modulation of the NF-κB signaling pathway. Our results indicated that bacterial metabolite, 2,3-butanediol has a negative regulatory effect on host innate immunity response, suggesting bacteria may use some metabolites for host immune evasion.
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Duncan, Robert Wayne. "The host-pathogen interaction and breeding and genetics of resistance for common bacterial blight of common bean (Phaseolus vulgaris L.) caused by Xanthomonas campestris pv. phaseoli and X. c. pv. phaseoli var. fuscans." Diss., 2009. http://proquest.umi.com/pqdweb?did=1978112521&sid=1&Fmt=2&clientId=48051&RQT=309&VName=PQD.
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