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Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus

2019; Nature Portfolio; Volume: 572; Issue: 7771 Linguagem: Inglês

10.1038/s41586-019-1501-z

1476-4687

Sohn G. Kim, Simone Becattini, Thomas Moody, Pavel V. Shliaha, Eric R. Littmann, Ruth Seok, Mergim Gjonbalaj, Vincent Eaton, Emily Fontana, Luigi A. Amoretti, Roberta J. Wright, Silvia Caballero, Zhong-Min Wang, Hea-Jin Jung, Sejal Morjaria, Ingrid M. Leiner, Weige Qin, Rúben J. Ramos, Justin R. Cross, Seiko Narushima, Kenya Honda, Jonathan U. Peled, Ronald C. Hendrickson, Ying Taur, Marcel R.M. van den Brink, Eric G. Pamer,

Clostridium difficile and Clostridium perfringens research

Intestinal commensal bacteria can inhibit dense colonization of the gut by vancomycin-resistant Enterococcus faecium (VRE), a leading cause of hospital-acquired infections1,2. A four-strained consortium of commensal bacteria that contains Blautia producta BPSCSK can reverse antibiotic-induced susceptibility to VRE infection3. Here we show that BPSCSK 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 BPSCSK and L. lactis in vitro, only BPSCSK colonizes the colon and reduces VRE density in vivo. In comparison to nisin-A, the BPSCSK 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. The gut commensal Blautia producta secretes a lantibiotic that reduces colonization of the gut by the major pathogen vancomycin-resistant Enterococcus faecium, and transplantation of microbiota with high abundance of the lantibiotic gene enhances resistance to colonization in mice.