The small RNA chaperone Hfq is required for the virulence of Yersinia pseudotuberculosis.

Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
Infection and immunity (Impact Factor: 4.16). 03/2010; 78(5):2034-44. DOI: 10.1128/IAI.01046-09
Source: PubMed

ABSTRACT Bacterial small, noncoding RNAs (sRNAs) participate in the posttranscriptional regulation of gene expression, often by affecting protein translation, transcript stability, and/or protein activity. For proper function, many sRNAs rely on the chaperone Hfq, which mediates the interaction of the sRNA with its target mRNA. Recent studies have demonstrated that Hfq contributes to the pathogenesis of a number of bacterial species, suggesting that sRNAs play an essential role in the regulation of virulence. The enteric pathogen Yersinia pseudotuberculosis causes the disease yersiniosis. Here we show that Hfq is required by Y. pseudotuberculosis to cause mortality in an intragastric mouse model of infection, and a strain lacking Hfq is attenuated 1,000-fold compared to the wild type. Hfq is also required for virulence through the intraperitoneal route of infection and for persistence of the bacterium in the Peyer's patches, mesenteric lymph nodes, and spleen, suggesting a role for Hfq in systemic infection. Furthermore, the Deltahfq mutant of Y. pseudotuberculosis is hypermotile and displays increased production of a biosurfactant-like substance, reduced intracellular survival in macrophages, and decreased production of type III secretion effector proteins. Together, these data demonstrate that Hfq plays a critical role in the virulence of Y. pseudotuberculosis by participating in the regulation of multiple steps in the pathogenic process and further highlight the unique role of Hfq in the virulence of individual pathogens.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Author Summary Many bacterial pathogens cycle between environmental sources and mammalian hosts. Adaptation to the different natural habitats and host niches is achieved through complex regulatory networks which adjust synthesis of the large repertoire of crucial virulence factors and fitness determinants. To uncover underlying control circuits, we determined the first in-depth single-nucleotide resolution transcriptome of Yersinia . This revealed important novel genetic information, such as global locations of transcriptional start sites, non-coding RNAs, potential riboswitches and provided a set of virulence-relevant expression profiles, which constitute a valuable tool for the research community. The analysis further uncovered a temperature-induced global reprogramming of central metabolic functions, likely to support intestinal colonization of the pathogen. This is accompanied by a major reorganization of the CRP regulon, which involves a multitude of regulatory RNAs. The primary consequence is a fine-tuned, coordinated control of metabolism and virulence through a plethora of environmentally controlled regulatory RNAs allowing rapid adaptation and high flexibility during life-style changes.
    PLoS Genetics 02/2015; 11(3-3):e1005087. DOI:10.1371/journal.pgen.1005087 · 8.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cronobacter spp. is an opportunistic pathogen that causes neonatal meningitis and sepsis with high mortality in neonates. Despite the peril associated with Cronobacter infection, the mechanisms of pathogenesis are being unraveled. Hfq, which is known as an RNA chaperone, participates in the interaction with bacterial small RNAs (sRNAs) to regulate post-transcriptionally the expression of various genes. Recent studies have demonstrated that Hfq contributes to the pathogenesis of numerous species of bacteria, and its roles are varied between bacterial species. Here, we tried to elucidate the role of Hfq in C. sakazakii virulence. In the absence of hfq, C. sakazakii was highly attenuated in dissemination in vivo, showed defects in invasion (3-fold) into animal cells and survival (10(3)-fold) within host cells, and exhibited low resistance to hydrogen peroxide (10(2)-fold). Remarkably, the loss of hfq led to hyper-motility on soft agar, which is contrary to what has been observed in other pathogenic bacteria. The hyper-flagellated bacteria were likely to be attributable to the increased transcription of genes associated with flagella biosynthesis in a strain lacking hfq. Together, these data strongly suggest that hfq plays important roles in the virulence of C. sakazakii by participating in the regulation of multiple genes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Infection and Immunity 03/2015; 83(5). DOI:10.1128/IAI.03161-14 · 4.16 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lysobacter enzymogenes is an important biocontrol agent with the ability to produce a variety of lytic enzymes and novel antibiotics. Little is known about their regulatory mechanisms. Understanding these will be helpful for improving biocontrol of crop diseases and potential medical application. In the present study, we generated an hfq (encoding a putative ribonucleic acid chaperone) deletion mutant, and then utilized a new genomic marker-free method to construct an hfq-complemented strain. We showed for the first time that Hfq played a pleiotropic role in regulating the antibacterial antibiotic biosynthesis and extracellular lytic enzyme activity in L. enzymogenes. Mutation of hfq significantly increased the yield of WAP-8294A2 (an antibacterial antibiotic) as well as the transcription of its key biosynthetic gene, waps1. However, inactivation of hfq almost abolished the extracellular chitinase activity and remarkably decreased the activity of both extracellular protease and cellulase in L. enzymogenes. We further showed that the regulation of hfq in extracellular chitinase production was in part through the impairment of the secretion of chitinase A. Collectively, our results reveal the regulatory roles of hfq in antibiotic metabolite and extracellular lytic enzymes in the underexplored genus of Lysobacter.
    Microbial Biotechnology 02/2015; 8(3). DOI:10.1111/1751-7915.12246 · 3.21 Impact Factor