Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus

Abstract

Intestinal commensal bacteria can inhibit dense colonization of the gut by vancomycin-resistant Enterococcus faecium (VRE), a leading cause of hospital-acquired infections^1,2. A four-strained consortium of commensal bacteria that contains Blautia producta BP_SCSK can reverse antibiotic-induced susceptibility to VRE infection³. Here we show that BP_SCSK reduces growth of VRE by secreting a lantibiotic that is similar to the nisin-A produced by Lactococcus lactis. Although the growth of VRE is inhibited by BP_SCSK and L. lactis in vitro, 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 of VRE infection, high abundance of the lantibiotic gene is associated with reduced density of E. faecium. In germ-free mice transplanted with patient-derived faeces, resistance to VRE colonization correlates with abundance of the lantibiotic gene. Lantibiotic-producing commensal strains of the gastrointestinal tract reduce colonization by VRE and represent potential probiotic agents to re-establish resistance to VRE.