Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus

Intestinal commensal bacteria can inhibit dense gut colonization by vancomycin-resistant Enterococcus faecium (VRE), a leading cause of hospital-acquired infections (1, 2). A consortium of commensal bacteria containing Blautia producta BP(SCSK) can reverse antibiotic-induced susceptibility to VRE infection (3). Herein we demonstrate that BP(SCSK) reduces VRE growth by secreting a lantibiotic similar to nisin-A produced by Lactococcus lactis. Although in vitro VRE growth is inhibited by BP(SCSK) and L. lactis, only BP(SCSK) colonizes the colon and reduces VRE density in vivo. In comparison to nisin-A, the BP(SCSK) lantibiotic has reduced activity against intestinal commensal bacteria. In patients at high risk for VRE infection, high lantibiotic gene abundance is associated with reduced E. faecium density. In germ free mice transplanted with patient-derived feces, resistance to VRE colonization correlates with lantibiotic gene abundance. Lantibiotic-producing commensal strains of the gastrointestinal tract reduce VRE colonization and represent potential probiotic agents to reestablish resistance to VRE.