Transcriptional Profiling of Neisseria meningitidis Interacting with Human Epithelial Cells in a Long-Term
            <i>In Vitro</i>
            Colonization Model

Hey, Ariann; Li, Mingshi; Hudson, Michael J.; Langford, Paul R.; Kroll, J. Simon

doi:10.1128/iai.00397-13

Cited by 26 publications

(23 citation statements)

References 58 publications

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“…We are also grateful to Ming-Shi Li (Imperial College, London) for the sharing microarray data associated with the study described in Hey et al, (2013). This work was supported by the German Research Foundation (DFG) grant SCHO 1322/1-1.…”

mentioning

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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mentioning

confidence: 99%

Metabolism and virulence in Neisseria meningitidis

Schoen

Kischkies

Elias

et al. 2014

Front. Cell. Infect. Microbiol.

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“…ingitidis, the PNPase homolog has been shown to be upregulated during long-term colonization of human epithelial cells in vitro (35).…”

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confidence: 99%

Neisseria meningitidis Polynucleotide Phosphorylase Affects Aggregation, Adhesion, and Virulence

et al. 2016

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Neisseria meningitidis autoaggregation is an important step during attachment to human cells. Aggregation is mediated by type IV pili and can be modulated by accessory pilus proteins, such as PilX, and posttranslational modifications of the major pilus subunit PilE. The mechanisms underlying the regulation of aggregation remain poorly characterized. Polynucleotide phosphorylase (PNPase) is a 3=-5= exonuclease that is involved in RNA turnover and the regulation of small RNAs. In this study, we biochemically confirm that NMC0710 is the N. meningitidis PNPase, and we characterize its role in N. meningitidis pathogenesis. We show that deletion of the gene encoding PNPase leads to hyperaggregation and increased adhesion to epithelial cells. The aggregation induced was found to be dependent on pili and to be mediated by excessive pilus bundling. PNPase expression was induced following bacterial attachment to human cells. Deletion of PNPase led to global transcriptional changes and the differential regulation of 469 genes. We also demonstrate that PNPase is required for full virulence in an in vivo model of N. meningitidis infection. The present study shows that PNPase negatively affects aggregation, adhesion, and virulence in N. meningitidis.

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“…S5). The major outer membrane proteins (OMPs) PorB and RmpM, which we considered as controls in a nonimmunogenic environment, showed stable expression .…”

Section: Resultsmentioning

confidence: 99%

“…S5). The major outer membrane proteins (OMPs) PorB and RmpM, which we considered as controls in a nonimmunogenic environment, showed stable expression [17,53,54]. Table 1 was generated to validate the results obtained with LC-MS E and to create an overview of the genes with robust experimental evidence of regulation by Hfq.…”

Section: Results Of Proteomic Analysis Of Wt Vs Dhfqmentioning

confidence: 99%

The Hfq regulon of Neisseria meningitidis

et al. 2017

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The conserved RNA ‐binding protein, Hfq, has multiple regulatory roles within the prokaryotic cell, including promoting stable duplex formation between small RNA s and mRNA s, and thus hfq deletion mutants have pleiotropic phenotypes. Previous proteome and transcriptome studies of Neisseria meningitidis have generated limited insight into differential gene expression due to Hfq loss. In this study, reversed‐phase liquid chromatography combined with data‐independent alternate scanning mass spectrometry ( LC ‐ MS E ) was utilized for rapid high‐resolution quantitative proteomic analysis to further elucidate the differentially expressed proteome of a meningococcal hfq deletion mutant. Whole‐cell lysates of N. meningitidis serogroup B H44/76 wild‐type (wt) and H44/76Δ hfq (Δ hfq ) grown in liquid growth medium were subjected to tryptic digestion. The resulting peptide mixtures were separated by liquid chromatography ( LC ) prior to analysis by mass spectrometry ( MS E ). Differential expression was analyzed by Student's t ‐test with control for false discovery rate ( FDR ). Reliable quantitation of relative expression comparing wt and Δ hfq was achieved with 506 proteins (20%). Upon FDR control at q ≤ 0.05, 48 up‐ and 59 downregulated proteins were identified. From these, 81 were identified as novel Hfq‐regulated candidates, while 15 proteins were previously found by SDS / PAGE / MS and 24 with microarray analyses. Thus, using LC ‐ MS E we have expanded the repertoire of Hfq‐regulated proteins. In conjunction with previous studies, a comprehensive network of Hfq‐regulated proteins was constructed and differentially expressed proteins were found to be involved in a large variety of cellular processes. The results and comparisons with other gram‐negative model systems, suggest still unidentified sRNA analogs in N. meningitidis .

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Transcriptional Profiling of Neisseria meningitidis Interacting with Human Epithelial Cells in a Long-Term In Vitro Colonization Model

Cited by 26 publications

References 58 publications

Metabolism and virulence in Neisseria meningitidis

Metabolism and virulence in Neisseria meningitidis

Neisseria meningitidis Polynucleotide Phosphorylase Affects Aggregation, Adhesion, and Virulence

The Hfq regulon of Neisseria meningitidis

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