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 NarushimaKenya Honda, Jonathan U. Peled, Ronald C. Hendrickson, Ying Taur, Marcel R.M. van den Brink, Eric G. Pamer

Research output: Contribution to journalLetter

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)665-669
Number of pages5
JournalNature
Volume572
Issue number7771
DOIs
Publication statusPublished - 2019 Aug 29

Fingerprint

Enterococcus faecium
Bacteriocins
Microbiota
Lactococcus lactis
Bacteria
Vancomycin-Resistant Enterococci
Probiotics
Growth
Feces
Genes
Gastrointestinal Tract
Colon
Anti-Bacterial Agents

ASJC Scopus subject areas

  • General

Cite this

Kim, S. G., Becattini, S., Moody, T. U., Shliaha, P. V., Littmann, E. R., Seok, R., ... Pamer, E. G. (2019). Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus. Nature, 572(7771), 665-669. https://doi.org/10.1038/s41586-019-1501-z

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

In: Nature, Vol. 572, No. 7771, 29.08.2019, p. 665-669.

Research output: Contribution to journalLetter

Kim, SG, Becattini, S, Moody, TU, Shliaha, PV, Littmann, ER, Seok, R, Gjonbalaj, M, Eaton, V, Fontana, E, Amoretti, L, Wright, R, Caballero, S, Wang, ZMX, Jung, HJ, 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 2019, 'Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus', Nature, vol. 572, no. 7771, pp. 665-669. https://doi.org/10.1038/s41586-019-1501-z
Kim SG, Becattini S, Moody TU, Shliaha PV, Littmann ER, Seok R et al. Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus. Nature. 2019 Aug 29;572(7771):665-669. https://doi.org/10.1038/s41586-019-1501-z
Kim, Sohn G. ; Becattini, Simone ; Moody, Thomas U. ; Shliaha, Pavel V. ; Littmann, Eric R. ; Seok, Ruth ; Gjonbalaj, Mergim ; Eaton, Vincent ; Fontana, Emily ; Amoretti, Luigi ; Wright, Roberta ; Caballero, Silvia ; Wang, Zhong Min X. ; Jung, Hea Jin ; Morjaria, Sejal M. ; Leiner, Ingrid M. ; Qin, Weige ; Ramos, Ruben J.J.F. ; Cross, Justin R. ; Narushima, Seiko ; Honda, Kenya ; Peled, Jonathan U. ; Hendrickson, Ronald C. ; Taur, Ying ; van den Brink, Marcel R.M. ; Pamer, Eric G. / Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus. In: Nature. 2019 ; Vol. 572, No. 7771. pp. 665-669.
@article{66daba91e3ff4cf48a5366eedfc3b43d,
title = "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 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.",
author = "Kim, {Sohn G.} and Simone Becattini and Moody, {Thomas U.} and Shliaha, {Pavel V.} and Littmann, {Eric R.} and Ruth Seok and Mergim Gjonbalaj and Vincent Eaton and Emily Fontana and Luigi Amoretti and Roberta Wright and Silvia Caballero and Wang, {Zhong Min X.} and Jung, {Hea Jin} and Morjaria, {Sejal M.} and Leiner, {Ingrid M.} and Weige Qin and Ramos, {Ruben J.J.F.} and Cross, {Justin R.} and Seiko Narushima and Kenya Honda and Peled, {Jonathan U.} and Hendrickson, {Ronald C.} and Ying Taur and {van den Brink}, {Marcel R.M.} and Pamer, {Eric G.}",
year = "2019",
month = "8",
day = "29",
doi = "10.1038/s41586-019-1501-z",
language = "English",
volume = "572",
pages = "665--669",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "7771",

}

TY - JOUR

T1 - Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus

AU - Kim, Sohn G.

AU - Becattini, Simone

AU - Moody, Thomas U.

AU - Shliaha, Pavel V.

AU - Littmann, Eric R.

AU - Seok, Ruth

AU - Gjonbalaj, Mergim

AU - Eaton, Vincent

AU - Fontana, Emily

AU - Amoretti, Luigi

AU - Wright, Roberta

AU - Caballero, Silvia

AU - Wang, Zhong Min X.

AU - Jung, Hea Jin

AU - Morjaria, Sejal M.

AU - Leiner, Ingrid M.

AU - Qin, Weige

AU - Ramos, Ruben J.J.F.

AU - Cross, Justin R.

AU - Narushima, Seiko

AU - Honda, Kenya

AU - Peled, Jonathan U.

AU - Hendrickson, Ronald C.

AU - Taur, Ying

AU - van den Brink, Marcel R.M.

AU - Pamer, Eric G.

PY - 2019/8/29

Y1 - 2019/8/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85071284500&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071284500&partnerID=8YFLogxK

U2 - 10.1038/s41586-019-1501-z

DO - 10.1038/s41586-019-1501-z

M3 - Letter

C2 - 31435014

AN - SCOPUS:85071284500

VL - 572

SP - 665

EP - 669

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 7771

ER -