The RNA chaperone Hfq is involved in stress tolerance and virulence in uropathogenic Proteus mirabilis

• Published in: PloS one 2014-01, Vol.9 (1), p.e85626
• Main Authors: Wang, Min-Cheng, Chien, Hsiung-Fei, Tsai, Yi-Lin, Liu, Ming-Che, Liaw, Shwu-Jen
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analysis; Animals; Antibiotics; Bacteria; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - physiology; Base Sequence; Biofilms; Biology; Biotechnology; Bladder; Cell survival; Chromosomes; Cytokines - biosynthesis; DNA Primers; Drug development; Drugs; E coli; Escherichia coli; Flagella; Gene expression; Gene Knockout Techniques; Health aspects; Helicobacter pylori; Homeostasis; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Infections; Interleukin 8; Kidneys; Laboratory animals; Macrophages; Male; Medicine; Membrane permeability; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Molecular Chaperones - chemistry; Molecular Chaperones - genetics; Molecular Chaperones - physiology; Molecular Sequence Data; Motility; Osmotic Pressure; Pathogenesis; Pathogens; Permeability; Plasmids; Proteins; Proteus mirabilis; Proteus mirabilis - metabolism; Proteus mirabilis - pathogenicity; Proteus mirabilis - physiology; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Ribonucleic acid; RNA; Salmonella; Sequence Homology, Amino Acid; Stationary phase; Stress; Stress response; Stresses; Urinary bladder; Urinary tract; Urinary Tract - metabolism; Urinary Tract - microbiology; Urinary tract infections; Urogenital system; Virulence; Virulence - physiology; Virulence factors; Wound infection
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0085626

Hfq is a bacterial RNA chaperone involved in the riboregulation of diverse genes via small noncoding RNAs. Here, we show that Hfq is critical for the uropathogenic Proteus mirabilis to effectively colonize the bladder and kidneys in a murine urinary tract infection (UTI) model and to establish burned wound infection of the rats. In this regard, we found the hfq mutant induced higher IL-8 and MIF levels of uroepithelial cells and displayed reduced intra-macrophage survival. The loss of hfq affected bacterial abilities to handle H2O2 and osmotic pressures and to grow at 50 °C. Relative to wild-type, the hfq mutant had reduced motility, fewer flagella and less hemolysin expression and was less prone to form biofilm and to adhere to and invade uroepithelial cells. The MR/P fimbrial operon was almost switched to the off phase in the hfq mutant. In addition, we found the hfq mutant exhibited an altered outer membrane profile and had higher RpoE expression, which indicates the hfq mutant may encounter increased envelope stress. With the notion of envelope disturbance in the hfq mutant, we found increased membrane permeability and antibiotic susceptibilities in the hfq mutant. Finally, we showed that Hfq positively regulated the RpoS level and tolerance to H2O2 in the stationary phase seemed largely mediated through the Hfq-dependent RpoS expression. Together, our data indicate that Hfq plays a critical role in P. mirabilis to establish UTIs by modulating stress responses, surface structures and virulence factors. This study suggests Hfq may serve as a scaffold molecule for development of novel anti-P. mirabilis drugs and P. mirabilis hfq mutant is a vaccine candidate for preventing UTIs.