Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits

Infection with antibiotic- resistant bacteria, such as vancomycin-resistant Enterococcus ( VRE), is a dangerous and costly complication of broad- spectrum antibiotic therapy(1,2). How antibiotic-mediated elimination of commensal bacteria promotes infection by antibiotic- resistant bacteria is a fertile area for speculation with few defined mechanisms. Here we demonstrate that antibiotic treatment of mice notably downregulates intestinal expression of RegIII gamma ( also known as Reg3g), a secreted C- type lectin that kills Gram- positive bacteria, including VRE. Downregulation of RegIII gamma markedly decreases in vivo killing of VRE in the intestine of antibiotic- treated mice. Stimulation of intestinal Toll- like receptor 4 by oral administration of lipopolysaccharide re-induces RegIII gamma, thereby boosting innate immune resistance of antibiotic-treated mice against VRE. Compromised mucosal innate immune defence, as induced by broad- spectrum antibiotic therapy, can be corrected by selectively stimulating mucosal epithelial Toll- like receptors, providing a potential therapeutic approach to reduce colonization and infection by antibiotic- resistant microbes.