The majority of genes in the pathogenic Neisseria species are present in non-pathogenic Neisseria lactamica, including those designated as 'virulence genes'

Snyder, Lori; Saunders, N.

doi:10.1186/1471-2164-7-128

Cited by 110 publications

(94 citation statements)

References 39 publications

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“…Spot data were extracted from images and manually flagged to remove artifacts before fusion. Fused data were filtered according to the pON value (20). Spots with pON values Ͻ0.5 in both channels were excluded to eliminate the bias generated by the inclusion of unhybridized spots in the statistical interpretation of the data, and the data were globally adjusted such that the mean rRNA ratio was 1.0.…”

Section: Strains Plasmids Oligonucleotide Primers and Gene Identifmentioning

confidence: 99%

Coordinated Regulation of the Neisseria gonorrhoeae-truncated Denitrification Pathway by the Nitric Oxide-sensitive Repressor, NsrR, and Nitrite-insensitive NarQ-NarP

Overton

Whitehead

et al. 2006

Journal of Biological Chemistry

123

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Neisseria gonorrhoeae survives anaerobically by reducing nitrite to nitrous oxide catalyzed by the nitrite and nitric oxide reductases, AniA and NorB. P aniA is activated by FNR (regulator of fumarate and nitrate reduction), the two-component regulatory system NarQ-NarP, and induced by nitrite; P norB is induced by NO independently of FNR by an uncharacterized mechanism. We report the results of microarray analysis, bioinformatic analysis, and chromatin immunoprecipitation, which revealed that only five genes with readily identified NarP-binding sites are differentially expressed in narP ؉ and narP strains. These include three genes implicated in the truncated gonococcal denitrification pathway: aniA, norB, and narQ. We also report that (i) nitrite induces aniA transcription in a narP mutant; (ii) nitrite induction involves indirect inactivation by nitric oxide of a gonococcal repressor, NsrR, identified from a multigenome bioinformatic study; (iii) in an nsrR mutant, aniA, norB, and dnrN (encoding a putative reactive nitrogen species response protein) were expressed constitutively in the absence of nitrite, suggesting that NsrR is the only NO-sensing transcription factor in N. gonorrhoeae; and (iv) NO rather than nitrite is the ligand to which NsrR responds. When expressed in Escherichia coli, gonococcal NarQ and chimaeras of E. coli and gonococcal NarQ are ligand-insensitive and constitutively active: a "locked-on" phenotype. We conclude that genes involved in the truncated denitrification pathway of N. gonorrhoeae are key components of the small NarQP regulon, that NarP indirectly regulates P norB by stimulating NO production by AniA, and that NsrR plays a critical role in enabling gonococci to evade NO generated as a host defense mechanism.In contrast to Escherichia coli that can inhabit a variety of environments and utilize numerous carbon sources and electron acceptors, some niche dwellers such as the obligate human pathogen Neisseria gonorrhoeae are far less versatile. The gonococcus can grow aerobically using glucose, lactate, or pyruvate as carbon sources and electron donors, and for many years it was thought to be an obligate aerobe. However, following the isolation of gonococci from patients alongside obligate anaerobes, it became clear that they could survive in the absence of oxygen in vivo using nitrite as an alternative electron acceptor (1, 2). Although gonococci express both a copper-containing nitrite reductase, AniA (NGO1276), and a single subunit nitric oxide reductase, NorB (NGO1275), which reduce nitrite via nitric oxide to nitrous oxide (2-5), denitrification is incomplete, because they lack genes for nitrate reduction, and there is a premature stop codon in the nitrous oxide reductase gene (nosZ, XNG1300), and the putative regulator of the nitrous oxide reduction genes, nosR (XNG1301), is also degenerate (see Fig. 1A). During oxygen-limited or anaerobic growth, AniA is the major anaerobically induced outer membrane protein (6). It is expressed by bacteria infecting patients, confirming th...

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Section: Strains Plasmids Oligonucleotide Primers and Gene Identifmentioning

confidence: 99%

Coordinated Regulation of the Neisseria gonorrhoeae-truncated Denitrification Pathway by the Nitric Oxide-sensitive Repressor, NsrR, and Nitrite-insensitive NarQ-NarP

Overton

Whitehead

et al. 2006

Journal of Biological Chemistry

123

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“…In turn, molecular epidemiology has provided clear observational evidence for a significant association between certain bacterial genotypes (hyperinvasive lineages) and IMD [5]. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous evidence of the presence of indispensable virulence factors [6, 7]. …”

Section: Introductionmentioning

confidence: 99%

Comparative Genome Sequencing Reveals Within-Host Genetic Changes in Neisseria meningitidis during Invasive Disease

et al. 2017

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Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation. In line with the hypothesis that phase variation evolved as an adaptation to colonize diverse hosts, computational comparisons of all 27 to date completely sequenced and annotated meningococcal genomes retrieved from public databases showed that contingency genes are indeed enriched for genes involved in host interactions. To assess within-host genetic changes in meningococci, we further used ultra-deep whole-genome sequencing of throat-blood strain pairs isolated from four patients suffering from invasive meningococcal disease. We detected up to three mutations per strain pair, affecting predominantly contingency genes involved in type IV pilus biogenesis. However, there was not a single (set) of mutation(s) that could invariably be found in all four pairs of strains. Phenotypic assays further showed that these genetic changes were generally not associated with increased serum resistance, higher fitness in human blood ex vivo or differences in the interaction with human epithelial and endothelial cells in vitro. In conclusion, we hypothesize that virulence of meningococci results from accidental emergence of invasive variants during carriage and without within host evolution of invasive phenotypes during disease progression in vivo.

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“…In fact, many of the so called meningococcal “virulence genes” have also been found in purely commensal neisserial species (Snyder and Saunders, 2006; Marri et al, 2010). Likewise, although statistically significant associations between some mobile genetic elements and hyperinvasive lineages have been found in genome-wide analyses the potential mechanistic contribution if any of these elements to virulence still remains elusive (Bille et al, 2008; Joseph et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Metabolism and virulence in Neisseria meningitidis

Schoen

Kischkies

Elias

et al. 2014

Front. Cell. Infect. Microbiol.

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A longstanding question in infection biology addresses the genetic basis for invasive behavior in commensal pathogens. A prime example for such a pathogen is Neisseria meningitidis. On the one hand it is a harmless commensal bacterium exquisitely adapted to humans, and on the other hand it sometimes behaves like a ferocious pathogen causing potentially lethal disease such as sepsis and acute bacterial meningitis. Despite the lack of a classical repertoire of virulence genes in N. meningitidis separating commensal from invasive strains, molecular epidemiology suggests that carriage and invasive strains belong to genetically distinct populations. In recent years, it has become increasingly clear that metabolic adaptation enables meningococci to exploit host resources, supporting the concept of nutritional virulence as a crucial determinant of invasive capability. Here, we discuss the contribution of core metabolic pathways in the context of colonization and invasion with special emphasis on results from genome-wide surveys. The metabolism of lactate, the oxidative stress response, and, in particular, glutathione metabolism as well as the denitrification pathway provide examples of how meningococcal metabolism is intimately linked to pathogenesis. We further discuss evidence from genome-wide approaches regarding potential metabolic differences between strains from hyperinvasive and carriage lineages and present new data assessing in vitro growth differences of strains from these two populations. We hypothesize that strains from carriage and hyperinvasive lineages differ in the expression of regulatory genes involved particularly in stress responses and amino acid metabolism under infection conditions.

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The majority of genes in the pathogenic Neisseria species are present in non-pathogenic Neisseria lactamica, including those designated as 'virulence genes'

Cited by 110 publications

References 39 publications

Coordinated Regulation of the Neisseria gonorrhoeae-truncated Denitrification Pathway by the Nitric Oxide-sensitive Repressor, NsrR, and Nitrite-insensitive NarQ-NarP

Coordinated Regulation of the Neisseria gonorrhoeae-truncated Denitrification Pathway by the Nitric Oxide-sensitive Repressor, NsrR, and Nitrite-insensitive NarQ-NarP

Comparative Genome Sequencing Reveals Within-Host Genetic Changes in Neisseria meningitidis during Invasive Disease

Metabolism and virulence in Neisseria meningitidis

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