Colonization resistance against genetically modifiedEscherichia coliK12 (W3110) strains is abrogated following broad-spectrum antibiotic treatment and acute ileitis

Abstract

Escherichia coli K12 (EcK12) is commonly used for gene technology purposes and regarded as a security strain due to its inability to adhere to epithelial cells. The conventional intestinal microbiota composition is critical for physiological colonization resistance against most bacterial species including pathogens. We were therefore interested whether intestinal colonization by a genetically modified EcK12 (W3110) strain carrying a chloramphenicol resistance cassette was facilitated following broad-spectrum antibiotic treatment eradicating the intestinal microbiota or induction of small intestinal inflammation accompanied by distinct microbiota shifts. Whereas conventional C57BL/6 and BALB/c mice had virtually expelled the EcK12 (W3110) strain within the first 3 days upon peroral infection, EcK12 (W3110) could establish within the small and large intestines of gnotobiotic mice generated by quintuple antibiotic treatment. Gnotobiotic mice perorally infected with EcK12 (W3110) plus fecal transplant from conventional donors harbored lower intestinal EcK12 (W3110) loads compared to animals challenged with EcK12 (W3110) alone. Furthermore, EcK12 (W3110) infection of conventional mice after but not before induction of ileitis resulted in stable colonization of ileum and colon by EcK12 (W3110). Taken together, broad-spectrum antibiotic treatment and intestinal inflammation compromise colonization resistance and thus facilitate colonization of the intestinal tract with genetically modified EcK12 security strains.