Functional genomics of Neisseria meningitidis pathogenesis

Sun, Yaohui; Bakshi, Sharmila; Chalmers, Ronald; Tang, Christoph M.

doi:10.1038/81380

Cited by 189 publications

(172 citation statements)

References 19 publications

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“…This is in agreement with the finding in Ralstonia solanacearum that a knockout of ampD, involved in peptidoglycan synthesis, results in decreased plant infection (271). STM showed that Neisseria meningitidis AmpD is necessary during rat infection (267).…”

Section: Genes Involved In Cell Envelope Structure and Modificationsupporting

confidence: 92%

Unraveling the Secret Lives of Bacteria: Use of In Vivo Expression Technology and Differential Fluorescence Induction Promoter Traps as Tools for Exploring Niche-Specific Gene Expression

Rediers

Rainey

Vanderleyden

et al. 2005

Microbiol Mol Biol Rev

141

120

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A major challenge for microbiologists is to elucidate the strategies deployed by microorganisms to adapt to and thrive in highly complex and dynamic environments. In vitro studies, including those monitoring genomewide changes, have proven their value, but they can, at best, mimic only a subset of the ensemble of abiotic and biotic stimuli that microorganisms experience in their natural habitats. The widely used gene-to-phenotype approach involves the identification of altered niche-related phenotypes on the basis of gene inactivation. However, many traits contributing to ecological performance that, upon inactivation, result in only subtle or difficult to score phenotypic changes are likely to be overlooked by this otherwise powerful approach. Based on the premise that many, if not most, of the corresponding genes will be induced or upregulated in the environment under study, ecologically significant genes can alternatively be traced using the promoter trap techniques differential fluorescence induction and in vivo expression technology (IVET). The potential and limitations are discussed for the different IVET selection strategies and system-specific variants thereof. Based on a compendium of genes that have emerged from these promoter-trapping studies, several functional groups have been distinguished, and their physiological relevance is illustrated with follow-up studies of selected genes. In addition to confirming results from largely complementary approaches such as signature-tagged mutagenesis, some unexpected parallels as well as distinguishing features of microbial phenotypic acclimation in diverse environmental niches have surfaced. On the other hand, by the identification of a large proportion of genes with unknown function, these promoter-trapping studies underscore how little we know about the secret lives of bacteria and other microorganisms

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Section: Genes Involved In Cell Envelope Structure and Modificationsupporting

confidence: 92%

Unraveling the Secret Lives of Bacteria: Use of In Vivo Expression Technology and Differential Fluorescence Induction Promoter Traps as Tools for Exploring Niche-Specific Gene Expression

Rediers

Rainey

Vanderleyden

et al. 2005

Microbiol Mol Biol Rev

141

120

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“…meningitidis has several mechanisms to avoid lysis by the complement system, including sialylation of its LPS and expression of a polysaccharide capsule (21). Strains which express truncated LPS isoforms or lack a capsule are highly susceptible to complement-mediated lysis, and are markedly attenuated in animal models of bacteraemia (22)(23)(24)(25). The serogroup classification of N. meningitidis is based on the chemical composition of its polysaccharide capsule.…”

mentioning

confidence: 99%

Functional Significance of Factor H Binding toNeisseria meningitidis

Schneider

Exley

Chan

et al. 2006

The Journal of Immunology

Self Cite

220

197

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Neisseria meningitidis is an important cause of septicemia and meningitis. To cause disease, the bacterium must successfully survive in the bloodstream where it has to avoid being killed by host innate immune mechanisms, particularly the complement system. A number of pathogenic microbes bind factor H (fH), the negative regulator of the alternative pathway of complement activation, to promote their survival in vivo. In this study, we show that N. meningitidis binds fH to its surface. Binding to serogroups A, B, and C N. meningitidis strains was detected by FACS and Far Western blot analysis, and occurred in the absence of other serum factors such as C3b. Unlike Neisseria gonorrhoeae, binding of fH to N. meningitidis was independent of sialic acid on the bacterium, either as a component of its LPS or its capsule. Characterization of the major fH binding partner demonstrated that it is a 33-kDa protein; examination of insertion mutants showed that porins A and B, outer membrane porins expressed by N. meningitidis, do not contribute significantly to fH binding. We examined the physiological consequences of fH bound to the bacterial surface. We found that fH retains its activity as a cofactor of factor I when bound to the bacterium and contributes to the ability of N. meningitidis to avoid complement-mediated killing in the presence of human serum. Therefore, the recruitment of fH provides another mechanism by which this important human pathogen evades host innate immunity.

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“…58,59). STM has been applied to more that 30 pathogens, including MenB, where 65 novel genes required for infection that causes septicemia in infant rats were identified (60), and Helicobacter pylori, where 47 genes essential for colonization of the gerbil stomach were identified (61). Also of interest have been studies using TraSH to identify the mechanisms by which M. tuberculosis persists in the host (62) and those using GAMBIT to determine the complete set of genes required by H. influenzae for growth and viability in vitro (63).…”

Section: Functional Genomics: Essential Genes As Vaccine Candidatesmentioning

confidence: 99%

Vaccinology in the genome era

Rinaudo¹,

Telford²,

Rappuoli³

et al. 2009

J. Clin. Invest.

144

118

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Vaccination has played a significant role in controlling and eliminating life-threatening infectious diseases throughout the world, and yet currently licensed vaccines represent only the tip of the iceberg in terms of controlling human pathogens. However, as we discuss in this Review, the arrival of the genome era has revolutionized vaccine development and catalyzed a shift from conventional culture-based approaches to genome-based vaccinology. The availability of complete bacterial genomes has led to the development and application of high-throughput analyses that enable rapid targeted identification of novel vaccine antigens. Furthermore, structural vaccinology is emerging as a powerful tool for the rational design or modification of vaccine antigens to improve their immunogenicity and safety.

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Functional genomics of Neisseria meningitidis pathogenesis

Cited by 189 publications

References 19 publications

Unraveling the Secret Lives of Bacteria: Use of In Vivo Expression Technology and Differential Fluorescence Induction Promoter Traps as Tools for Exploring Niche-Specific Gene Expression

Unraveling the Secret Lives of Bacteria: Use of In Vivo Expression Technology and Differential Fluorescence Induction Promoter Traps as Tools for Exploring Niche-Specific Gene Expression

Functional Significance of Factor H Binding toNeisseria meningitidis

Vaccinology in the genome era

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