Abstract
SummaryWe 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.
Highlights
Antibiotic chemotherapy is often an effective treatment for bacterial infections, leading to a rapid reduction in bacterial burden, morbidity, and mortality
Daily oral treatments with Kan resulted in the number of shed C. rodentium plateauing at around 109 colony-forming units (CFUs)/g of feces for the duration of the study (Figure 1A), a phenomenon we term antibiotic-induced bacterial persistence (AIBP)
bioluminescent imaging (BLI) revealed that AIBP was accompanied by redistribution of the BL signal from the colon and cecum prior to Kan treatment to solely the cecum posttreatment (Figure 1B)
Summary
Antibiotic chemotherapy is often an effective treatment for bacterial infections, leading to a rapid reduction in bacterial burden, morbidity, and mortality. Unintentional targets of oral antibiotics are commensal bacteria, which provide a protective barrier against pathogens (Kamada et al, 2013; Zhang et al, 2013). Antibiotic-induced dysbiosis increases host susceptibility to bacterial colonization; by pre-treating mice with streptomycin pathogenic and non-pathogenic bacteria, e.g., Salmonella enterica serovar Typhimurium and Escherichia coli, can colonize the murine gastrointestinal tract, which is usually refractory to these strains (Barthel et al, 2003; Spees et al, 2013). In C57BL/6 mice, C. rodentium causes a selflimiting infection, without the need for antibiotic pre-treatment, and triggers robust colitis, colonic crypt hyperplasia (CCH), and dysbiosis (Collins et al, 2014). In which the LEE is not expressed, are avirulent, yet they can colonize germ-free mice (Kamada et al, 2012)
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