1. The CpxRA two-component system is essential for Citrobacter rodentium virulence.
- Author
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Thomassin JL, Giannakopoulou N, Zhu L, Gross J, Salmon K, Leclerc JM, Daigle F, Le Moual H, and Gruenheid S
- Subjects
- Animals, Bacterial Proteins genetics, Citrobacter rodentium genetics, Colon microbiology, Enteritis pathology, Gene Deletion, Genetic Complementation Test, Mice, Inbred C3H, Mice, Inbred C57BL, Protein Kinases genetics, Survival Analysis, Virulence Factors genetics, Bacterial Proteins metabolism, Citrobacter rodentium pathogenicity, Enteritis microbiology, Protein Kinases metabolism, Virulence Factors metabolism
- 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., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
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