Citrobacter rodentium Relies on Commensals for Colonization of the Colonic Mucosa

We investigated the role of commensals at the peak of infection with the colonic mouse pathogen Citrobacter rodentium. Bioluminescent and kanamycin (Kan)-resistant C. rodentium persisted avirulently in the cecal lumen of mice continuously treated with Kan. A single Kan treatment was sufficient to displace C. rodentium from the colonic mucosa, a phenomenon not observed following treatment with vancomycin (Van) or metronidazole (Met). Kan, Van, and Met induce distinct dysbiosis, suggesting C. rodentium relies on specific commensals for colonic colonization. Expression of the master virulence regulator ler is induced in germ-free mice, yet C. rodentium is only seen in the cecal lumen. Moreover, in conventional mice, a single Kan treatment was sufficient to displace C. rodentium constitutively expressing Ler from the colonic mucosa. These results show that expression of virulence genes is not sufficient for colonization of the colonic mucosa and that commensals are essential for a physiological infection course. A/E pathogens intimately adhere to the gut mucosa. Mullineaux-Sanders et al. demonstrate that inducing specific dysbiosis at the peak of murine infection with Citrobacter rodentium prevents mucosal colonization. This occurs via a mechanism independent of virulence gene expression modulation, indicating that enteric pathogens may rely on commensals for effective infection.