Bile Acid Induced Morphotype Switch Mediates Intestinal Colonization in Vancomycin Resistant <i>Enterococcus</i>

Abstract

Vancomycin resistant Enterococcus (VRE) is a highly antibiotic-resistant and readily transmissible pathogen that causes severe infections in hospitalized patients. We discovered that lithocholic acid (LCA), a secondary bile acid prevalent in the cecum and colon of mice and humans, impaired separation of growing VRE diplococci causing the formation of long chains, increasing biofilm formation and enhancing VRE’s ability to colonize the host intestine. Divalent cations reversed the switch to chaining and biofilm formation. Experimental evolution in the presence of LCA yielded mutations in yycG/walK and liaR that locked VRE in diplococcal mode, impaired biofilm formation and increased susceptibility to Daptomycin. These strains were deficient in host colonization specifically by affecting VRE’s ability to compete with intestinal microbiota. This morphotype switch presents a non-bactericidal therapeutic target that may help to clear VRE from the intestines of dominated patients, as occurs frequently during hematopoietic stem cell transplantation.