Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus.

TitleMicrobiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus.
Publication TypeJournal Article
Year of Publication2019
AuthorsKim SG, Becattini S, Moody TU, Shliaha PV, Littmann ER, Seok R, Gjonbalaj M, Eaton V, Fontana E, Amoretti L, Wright R, Caballero S, Wang Z-MX, Jung H-J, Morjaria SM, Leiner IM, Qin W, Ramos RJJF, Cross JR, Narushima S, Honda K, Peled JU, Hendrickson RC, Taur Y, van den Brink MRM, Pamer EG
JournalNature
Volume572
Issue7771
Pagination665-669
Date Published2019 Aug
ISSN1476-4687
Abstract

Intestinal commensal bacteria can inhibit dense colonization of the gut by vancomycin-resistant Enterococcus faecium (VRE), a leading cause of hospital-acquired infections. A four-strained consortium of commensal bacteria that contains Blautia producta BP can reverse antibiotic-induced susceptibility to VRE infection. Here we show that BP 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 and L. lactis in vitro, only BP colonizes the colon and reduces VRE density in vivo. In comparison to nisin-A, the BP 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.

DOI10.1038/s41586-019-1501-z
Alternate JournalNature
PubMed ID31435014
PubMed Central IDPMC6717508
Grant ListU01 AI124275 / AI / NIAID NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
R01 AI095706 / AI / NIAID NIH HHS / United States
T34 GM007823 / GM / NIGMS NIH HHS / United States
R01 AI042135 / AI / NIAID NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States

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