The RNA Chaperone Hfq Is Important for Growth and Stress Tolerance in Francisella novicida

Chambers, Jacob R.; Bender, Kelly S.

doi:10.1371/journal.pone.0019797

Cited by 36 publications

(30 citation statements)

References 55 publications

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“…Biofilm formation could be an important factor in the infection process contributing to persistence and to the high incidence of clinical relapse (31,90). Hfq depletion increased C. difficile biofilm formation, as observed for hfq mutants of Francisella novicida and Moraxella catarrhalis (91,92). Interestingly, the expression of genes encoding cell wall-associated proteins and of sinR (CD2214) encoding an orthologue of the master biofilm regulator in B. subtilis (69) is induced in the Hfq-depleted strain.…”

Section: Discussionmentioning

confidence: 87%

“…In addition, a diguanylate cyclase (CD2887) and a phosphodiesterase (CD1616), involved in the turnover of c-di-GMP, a key molecule modulating cellular processes associated with community behavior, are inversely regulated when the Hfq level drops, suggesting that Hfq might influence c-di-GMP accumulation. Both Hfq and sRNAs participate in the regulatory networks controlling bacterial biofilms (14,17,(91)(92)(93). In E. coli and other enteric bacteria, Hfq-dependent sRNAs contribute to inverse regulation of the synthesis of flagella and biofilm matrix components during the transition to stationary phase (94)(95)(96)(97).…”

Section: Discussionmentioning

confidence: 99%

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Pleiotropic Role of the RNA Chaperone Protein Hfq in the Human Pathogen Clostridium difficile

et al. 2014

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cClostridium difficile is an emergent human pathogen and the most common cause of nosocomial diarrhea. Our recent data strongly suggest the importance of RNA-based mechanisms for the control of gene expression in C. difficile. In an effort to understand the function of the RNA chaperone protein Hfq, we constructed and characterized an Hfq-depleted strain in C. difficile. Hfq depletion led to a growth defect, morphological changes, an increased sensitivity to stresses, and a better ability to sporulate and to form biofilms. The transcriptome analysis revealed pleiotropic effects of Hfq depletion on gene expression in C. difficile, including genes encoding proteins involved in sporulation, stress response, metabolic pathways, cell wall-associated proteins, transporters, and transcriptional regulators and genes of unknown function. Remarkably, a great number of genes of the regulon dependent on sporulation-specific sigma factor, SigK, were upregulated in the Hfq-depleted strain. The altered accumulation of several sRNAs and interaction of Hfq with selected sRNAs suggest potential involvement of Hfq in these regulatory RNA functions. Altogether, these results suggest the pleiotropic role of Hfq protein in C. difficile physiology, including processes important for the C. difficile infection cycle, and expand our knowledge of Hfq-dependent regulation in Gram-positive bacteria.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Pleiotropic Role of the RNA Chaperone Protein Hfq in the Human Pathogen Clostridium difficile

et al. 2014

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“…A reducedvirulence phenotype in hfq mutants was also commonly observed in other Gram-negative pathogens, including Brucella abortus, Francisella tularensis, Neisseria meningitidis, Pseudomonas aeruginosa, and Yersinia pestis, and in the Gram-positive pathogen Listeria monocytogenes (28). Although Hfq has been implicated in controlling virulence in many bacterial pathogens, the regulatory targets of Hfq vary among species, from regulation of the T3SS (31,32) and stress tolerance (33,34) to biofilm formation (35). In some cases, the regulatory function of Hfq is still not clear (28).…”

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confidence: 87%

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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“…It has been reported that the functions of Hfq focus mainly on growth-dependent metabolism, resistance to stress, modulation of virulence and drug resistance [14,17e20]. For example, in Francisella novicida, Hfq was found to have a role in the stress response to osmotic changes, low pH, heat shock and oxidative stress [21]. The Hfq protein of enterohemorrhagic E. coli (EHEC) had an impact on virulence, cell growth and acid stress processes [22].…”

Section: Introductionmentioning

confidence: 99%

hfq regulates acid tolerance and virulence by responding to acid stress in Shigella flexneri

Yang

Wang

et al. 2015

Research in Microbiology

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Shigella flexneri is an important etiological agent of bacillary dysentery in developing countries. The Hfq protein is thought to play a major regulatory role in various cellular processes in this organism. However, the roles of Hfq in stress tolerance and virulence in S. flexneri in response to environmental stress have not been fully studied. In this study, hfq was highly expressed when S. flexneri was exposed to low pH. Growth retardation was observed in the hfq deletion mutant at pH values ranging from 5.0 to 7.0 and the survival rate of the mutant strain was reduced by 60% in acidic conditions (pH 3.0) compared with the wild-type strain. Additionally, competitive invasion assays in HeLa cells and lung invasion assays showed that the virulence of the hfq deletion mutant was significantly decreased. An evaluation of the mechanism revealed that, along with the expression of the Type III secretion system genes, acid resistance genes were also increased with acid stress. Interestingly, a statistically strong linear correlation was observed between the expression of hfq and Type III secretion system genes, as well as between hfq and acid resistance genes, under various pH conditions. In this study, we provide evidence that Hfq regulates genes related to acid resistance for survival under acid stress and controls virulence through the positive regulation of Type III secretion systems. Importantly, we propose that hfq is a key factor in maximal adaptation to host acid stress during infection, regulating acid stress tolerance and virulence in response to acid stress in S. flexneri.

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The RNA Chaperone Hfq Is Important for Growth and Stress Tolerance in Francisella novicida

Cited by 36 publications

References 55 publications

Pleiotropic Role of the RNA Chaperone Protein Hfq in the Human Pathogen Clostridium difficile

Pleiotropic Role of the RNA Chaperone Protein Hfq in the Human Pathogen Clostridium difficile

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

hfq regulates acid tolerance and virulence by responding to acid stress in Shigella flexneri

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