title: The CpxRA two-component system is essential for Citrobacter rodentium virulence.
abstract: Citrobacter rodentium is a murine intestinal pathogen used as a model for the foodborne human pathogens enterohemorrhagic Escherichia coli and enteropathogenic E. coli. During infection, these pathogens use two-component signal transduction systems to detect and adapt to changing environmental conditions. In E. coli, the CpxRA two-component signal transduction system responds to envelope stress by modulating the expression of a myriad of genes. Quantitative real-time PCR showed that cpxRA was expressed in the colon of C57BL/6J mice infected with C. rodentium. To determine whether CpxRA plays a role during C. rodentium infection, a cpxRA deletion strain was generated and found to have a colonization defect during infection. This defect was independent of an altered growth rate or a defective type III secretion system, and single-copy chromosomal complementation of cpxRA restored virulence. The C. rodentium strains were then tested in C3H/HeJ mice, a lethal intestinal infection model. Mice infected with the ΔcpxRA strain survived infection, whereas mice infected with the wild-type or complemented strains succumbed to infection. Furthermore, we found that the cpxRA expression level was higher during early infection than at a later time point. Taken together, these data demonstrate that the CpxRA two-component signal transduction system is essential for the in vivo virulence of C. rodentium. In addition, these data suggest that fine-tuned cpxRA expression is important for infection. This is the first study that identifies a C. rodentium two-component transduction system required for pathogenesis. This study further indicates that CpxRA is an interesting target for therapeutics against enteric pathogens.
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
authors.forename: Jenny-Lee
authors.initials: JL
authors.lastname: Thomassin
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
authors.forename: Natalia
authors.initials: N
authors.lastname: Giannakopoulou
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Gross
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
authors.forename: Kristiana
authors.initials: K
authors.lastname: Salmon
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
authors.forename: Jean-Mathieu
authors.initials: JM
authors.lastname: Leclerc
authors.affiliation: Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: France
authors.initials: F
authors.lastname: Daigle
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec, Canada Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Moual
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec, Canada samantha.gruenheid@mcgill.ca.
authors.forename: Samantha
authors.initials: S
authors.lastname: Gruenheid
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D044082:Citrobacter rodentium / Q000235:genetics / Q000472:pathogenicity*; D003106:Colon / Q000382:microbiology; D004751:Enteritis / Q000382:microbiology* / Q000473:pathology; D017353:Gene Deletion; D005816:Genetic Complementation Test; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; C085504:CpxR protein, Bacteria; D011494:Protein Kinases; C092472:CpxA protein, bacteria