Antibiotic treatment of patients undergoing complex medical treatments can deplete commensal bacterial strains from the intestinal microbiota, thereby reducing colonization resistance against a wide range of
antibiotic-resistant pathogens. Loss of colonization resistance can lead to marked expansion of
vancomycin-resistant Enterococcus faecium (VRE), Klebsiella pneumoniae, and Escherichia coli in the intestinal lumen, predisposing patients to bloodstream invasion and
sepsis. The impact of intestinal domination by these
antibiotic-resistant pathogens on mucosal immune defenses and epithelial and
mucin-mediated barrier integrity is unclear. We used a mouse model to study the impact of intestinal domination by
antibiotic-resistant bacterial species and strains on the colonic mucosa. Intestinal colonization with K. pneumoniae, Proteus mirabilis, or Enterobacter cloacae promoted greater recruitment of neutrophils to the colonic mucosa. To test the hypothesis that the residual microbiota influences the severity of
colitis caused by
infection with Clostridioides difficile, we coinfected mice that were colonized with
ampicillin-resistant bacteria with a virulent strain of C. difficile and monitored colonization and pathogenesis. Despite the compositional differences in the gut microbiota, the severity of C. difficile
infection (CDI) and mortality did not differ significantly between mice colonized with different
ampicillin-resistant bacterial species. Our results suggest that the virulence mechanisms enabling CDI and epithelial destruction outweigh the relatively minor impact of less-virulent
antibiotic-resistant intestinal bacteria on the outcome of CDI.