Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus

Sohn G. Kim, Simone Becattini, Thomas U. Moody, Pavel V. Shliaha, Eric R. Littmann, Ruth Seok, Mergim Gjonbalaj, Vincent Eaton, Emily Fontana, Luigi Amoretti, Roberta Wright, Silvia Caballero, Zhong-Min X. Wang, Hea-Jin Jung, Sejal M. Morjaria, Ingrid M. Leiner, Weige Qin, Ruben J. J. F. Ramos, Justin R. Cross, Seiko Narushima, Kenya Honda, Jonathan U. Peled, Ronald C. Hendrickson, Ying Taur, Marcel R. M. Brink and Eric G. Pamer ()
Additional contact information
Sohn G. Kim: Memorial Sloan Kettering Cancer Center
Simone Becattini: Memorial Sloan Kettering Cancer Center
Thomas U. Moody: Memorial Sloan Kettering Cancer Center
Pavel V. Shliaha: Memorial Sloan Kettering Cancer Center
Eric R. Littmann: Memorial Sloan Kettering Cancer Center
Ruth Seok: Memorial Sloan Kettering Cancer Center
Mergim Gjonbalaj: Memorial Sloan Kettering Cancer Center
Vincent Eaton: Memorial Sloan Kettering Cancer Center
Emily Fontana: Memorial Sloan Kettering Cancer Center
Luigi Amoretti: Memorial Sloan Kettering Cancer Center
Roberta Wright: Memorial Sloan Kettering Cancer Center
Silvia Caballero: Memorial Sloan Kettering Cancer Center
Zhong-Min X. Wang: Memorial Sloan Kettering Cancer Center
Hea-Jin Jung: Memorial Sloan Kettering Cancer Center
Sejal M. Morjaria: Memorial Sloan Kettering Cancer Center
Ingrid M. Leiner: Memorial Sloan Kettering Cancer Center
Weige Qin: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Ruben J. J. F. Ramos: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Justin R. Cross: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Seiko Narushima: RIKEN Center for Integrative Medical Sciences
Kenya Honda: RIKEN Center for Integrative Medical Sciences
Jonathan U. Peled: Weill Cornell Medical College
Ronald C. Hendrickson: Memorial Sloan Kettering Cancer Center
Ying Taur: Memorial Sloan Kettering Cancer Center
Marcel R. M. Brink: Memorial Sloan Kettering Cancer Center
Eric G. Pamer: Memorial Sloan Kettering Cancer Center

Nature, 2019, vol. 572, issue 7771, 665-669

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41586-019-1501-z

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