title: New aspects of RpoE in uropathogenic Proteus mirabilis.
abstract: Proteus mirabilis is a common human pathogen causing recurrent or persistent urinary tract infections (UTIs). The underlying mechanisms for P. mirabilis to establish UTIs are not fully elucidated. In this study, we showed that loss of the sigma factor E (RpoE), mediating extracytoplasmic stress responses, decreased fimbria expression, survival in macrophages, cell invasion, and colonization in mice but increased the interleukin-8 (IL-8) expression of urothelial cells and swarming motility. This is the first study to demonstrate that RpoE modulated expression of MR/P fimbriae by regulating mrpI, a gene encoding a recombinase controlling the orientation of MR/P fimbria promoter. By real-time reverse transcription-PCR, we found that the IL-8 mRNA amount of urothelial cells was induced significantly by lipopolysaccharides extracted from rpoE mutant but not from the wild type. These RpoE-associated virulence factors should be coordinately expressed to enhance the fitness of P. mirabilis in the host, including the avoidance of immune attacks. Accordingly, rpoE mutant-infected mice displayed more immune cell infiltration in bladders and kidneys during early stages of infection, and the rpoE mutant had a dramatically impaired ability of colonization. Moreover, it is noteworthy that urea (the major component in urine) and polymyxin B (a cationic antimicrobial peptide) can induce expression of rpoE by the reporter assay, suggesting that RpoE might be activated in the urinary tract. Altogether, our results indicate that RpoE is important in sensing environmental cues of the urinary tract and subsequently triggering the expression of virulence factors, which are associated with the fitness of P. mirabilis, to build up a UTI.
authors.affiliation: Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
authors.forename: Ming-Che
authors.initials: MC
authors.lastname: Liu
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Kuan-Ting
authors.initials: KT
authors.lastname: Kuo
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Hsiung-Fei
authors.initials: HF
authors.lastname: Chien
authors.affiliation: Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Tsai
authors.affiliation: Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China sjliaw@ntu.edu.tw.
authors.forename: Shwu-Jen
authors.initials: SJ
authors.lastname: Liaw
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology; D005260:Female; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011112:Polymyxin B / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011512:Proteus Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D011513:Proteus mirabilis / Q000187:drug effects / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D045522:Recombinases / Q000235:genetics / Q000378:metabolism; D012808:Sigma Factor / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D014508:Urea / Q000494:pharmacology; D014552:Urinary Tract Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D019459:Urothelium / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D014774:Virulence
chemical_list: D016209:Interleukin-8; D008070:Lipopolysaccharides; D045522:Recombinases; D012808:Sigma Factor; D014508:Urea; D011112:Polymyxin B