PLoS Pathogens (Dec 2024)

The gut microbiota-independent virulence of noninvasive bacterial pathogen Citrobacter rodentium.

  • Yue Liu,
  • Dongqing Xu,
  • Songwei Guo,
  • Shuyu Wang,
  • Hua Ding,
  • Catherine Siu,
  • Fengyi Wan

DOI
https://doi.org/10.1371/journal.ppat.1012758
Journal volume & issue
Vol. 20, no. 12
p. e1012758

Abstract

Read online

Attaching and effacing (A/E) bacterial pathogens consist of human pathogens enteropathogenic Escherichia coli, enterohemorrhagic E. coli and their murine equivalent Citrobacter rodentium (CR). Emerging evidence suggests that the complex pathogen-microbiota-host interactions are critical in conferring A/E pathogen infection-induced severe symptoms and lethality in immunocompromised hosts; however, the precise underlying mechanisms remain enigmatic. Here we report that CR infection causes severe colitis and mortality in interleukin 22 knockout (Il22-/-) and Rag1 knockout (Rag1-/-) mice under germ-free (GF) conditions. In a gut microbiota-independent manner, CR colonizes in GF Il22-/- and Rag1-/- animals, triggers colonic epithelial tissue damage and systemic dissemination of CR, and results in lethal infections. Pretreatment with cefoxitin, a broad-spectrum antibiotic, exacerbates CR-induced colitis and lethality in specific-pathogen-free (SPF) Il22-/- and Rag1-/- mice. Together our results reveal that CR possesses a gut microbiota-independent virulence, which is better illustrated during infections in immunocompromised hosts associated with severe outcomes.