The effect of <i>hfq</i> on global gene expression and virulence in <i>Neisseria gonorrhoeae</i>

Dietrich, Manuela; Munke, Rebekka; Gottschald, Marion; Ziska, Elke; Boettcher, Jan Peter; Mollenkopf, Hans-Joachim; Friedrich, Alexandra

doi:10.1111/j.1742-4658.2009.07234.x

Cited by 36 publications

(31 citation statements)

References 61 publications

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“…Consequently, an hfq mutant of S. Typhimurium was found to be highly attenuated in a mouse infection model (23). Similarly, experiments employing murine or rat infection models revealed a role of Hfq in the virulence of several pathogenic bacteria (24)(25)(26)(27)(28).…”

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confidence: 99%

The RNA Chaperone Hfq Is Required for Virulence of Bordetella pertussis

et al. 2013

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bBordetella pertussis is a Gram-negative pathogen causing the human respiratory disease called pertussis or whooping cough. Here we examined the role of the RNA chaperone Hfq in B. pertussis virulence. Hfq mediates interactions between small regulatory RNAs and their mRNA targets and thus plays an important role in posttranscriptional regulation of many cellular processes in bacteria, including production of virulence factors. We characterized an hfq deletion mutant (⌬hfq) of B. pertussis 18323 and show that the ⌬hfq strain produces decreased amounts of the adenylate cyclase toxin that plays a central role in B. pertussis virulence. Production of pertussis toxin and filamentous hemagglutinin was affected to a lesser extent. In vitro, the ability of the ⌬hfq strain to survive within macrophages was significantly reduced compared to that of the wild-type (wt) strain. The virulence of the ⌬hfq strain in the mouse respiratory model of infection was attenuated, with its capacity to colonize mouse lungs being strongly reduced and its 50% lethal dose value being increased by one order of magnitude over that of the wt strain. In mixedinfection experiments, the ⌬hfq strain was then clearly outcompeted by the wt strain. This requirement for Hfq suggests involvement of small noncoding RNA regulation in B. pertussis virulence.

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confidence: 99%

The RNA Chaperone Hfq Is Required for Virulence of Bordetella pertussis

et al. 2013

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“…The transcriptional regulators Hfq, PhoP (MisR), and Lrp were upregulated during prolonged (Ͼ24 h) cocultivation, establishing their importance in modulating genome-wide patterns of gene expression during established colonization. Hfq binds small RNAs and is widely involved in gene regulation: hfq mutants are attenuated for epithelial cell adherence (48). Employing proteomic approaches, two studies using meningococcal hfq mutants have identified a number of deregulated proteins (49,50).…”

Section: Discussionmentioning

confidence: 99%

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

Hey

Hudson

et al. 2013

Infect Immun

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Neisseria meningitidis is a commensal of humans that can colonize the nasopharyngeal epithelium for weeks to months and occasionally invades to cause life-threatening septicemia and meningitis. Comparatively little is known about meningococcal gene expression during colonization beyond those first few hours. In this study, the transcriptome of adherent serogroup B N. meningitidis strain MC58 was determined at intervals during prolonged cocultivation with confluent monolayers of the human respiratory epithelial cell line 16HBE14. At different time points up to 21 days, 7 to 14% of the meningococcal genome was found to be differentially regulated. The transcriptome of adherent meningococci obtained after 4 h of coculture was markedly different from that obtained after prolonged cocultivation (24 h, 96 h, and 21 days). Genes persistently upregulated during prolonged cocultivation included three genes (hfq, misR/phoP, and lrp) encoding global regulatory proteins. Many genes encoding known adhesins involved in epithelial adherence were upregulated, including those of a novel locus (spanning NMB0342 to NMB0348 [NMB0342-NMB0348]) encoding epithelial cell-adhesive function. Sixteen genes (including porA, porB, rmpM, and fbpA) encoding proteins previously identified by their immunoreactivity to sera from individuals colonized long term with serogroup B meningococci were also upregulated during prolonged cocultivation, indicating that our system models growth conditions in vivo during the commensal state. Surface-expressed proteins downregulated in the nasopharynx (and thus less subject to selection pressure) but upregulated in the bloodstream (and thus vulnerable to antibody-mediated bactericidal activity) should be interesting candidate vaccine antigens, and in this study, three new proteins fulfilling these criteria have been identified: NMB0497, NMB0866, and NMB1882.

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“…However, the role of Hfq as a virulence regulator is not universal among pathogens. For example, in Staphylococcus aureus, an hfq mutant, virulence for the worm Caenorhabditis elegans was not affected (48), and in Neisseria gonorrhoeae, the virulence of an hfq mutant was not altered in cell culture models (49).…”

Section: Discussionmentioning

confidence: 99%

Global Small RNA Chaperone Hfq and Regulatory Small RNAs Are Important Virulence Regulators in Erwinia amylovora

2013

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Hfq is a global small RNA (sRNA) chaperone that interacts with Hfq-regulated sRNAs and functions in the posttranscriptional regulation of gene expression. In this work, we identified Hfq to be a virulence regulator in the Gram-negative fire blight pathogen Erwinia amylovora. Deletion of hfq in E. amylovora Ea1189 significantly reduced bacterial virulence in both immature pear fruits and apple shoots. Analysis of virulence determinants in strain Ea1189⌬hfq showed that Hfq exerts pleiotropic regulation of amylovoran exopolysaccharide production, biofilm formation, motility, and the type III secretion system (T3SS). Further characterization of biofilm regulation by Hfq demonstrated that Hfq limits bacterial attachment to solid surfaces while promoting biofilm maturation. Characterization of T3SS regulation by Hfq revealed that Hfq positively regulates the translocation and secretion of the major type III effector DspE and negatively controls the secretion of the putative translocator HrpK and the type III effector Eop1. Lastly, 10 Hfq-regulated sRNAs were identified using a computational method, and two of these sRNAs, RprA and RyhA, were found to be required for the full virulence of E. amylovora.

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The effect of hfq on global gene expression and virulence in Neisseria gonorrhoeae

Cited by 36 publications

References 61 publications

The RNA Chaperone Hfq Is Required for Virulence of Bordetella pertussis

The RNA Chaperone Hfq Is Required for Virulence of Bordetella pertussis

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

Global Small RNA Chaperone Hfq and Regulatory Small RNAs Are Important Virulence Regulators in Erwinia amylovora

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