Structural modification of lipopolysaccharide conferred by mcr-1 in gram-negative ESKAPE pathogens

Yi Yun Liu, Courtney E. Chandler, Lisa M. Leung, Christi L. McElheny, Roberta T. Mettus, Robert M.Q. Shanks, Jian Hua Liu, David R. Goodlett, Robert K. Ernst, Yohei Doi

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

mcr-1 was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of Escherichia coli and Klebsiella pneumoniae in China and has subsequently been identified worldwide in various species of the family Enterobacteriaceae. mcr-1 encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-Acylated lipid A in E. coli. Here, we investigated the effects of mcr-1 on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens, which are often treated clinically by colistin. The effects of mcr-1 on colistin resistance were determined using MIC assays of laboratory and clinical strains of E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. Lipid A structural changes resulting from MCR-1 were analyzed by mass spectrometry. The introduction of mcr-1 led to colistin resistance in E. coli, K. pneumoniae, and A. baumannii but only moderately reduced susceptibility in P. aeruginosa. Phosphoethanolamine modification of lipid A was observed consistently for all four species. These findings highlight the risk of colistin resistance as a consequence of mcr-1 expression among ESKAPE pathogens, especially in K. pneumoniae and A. baumannii. Furthermore, the observation that lipid A structures were modified despite only modest increases in colistin MICs in some instances suggests more sophisticated surveillance methods may need to be developed to track the dissemination of mcr-1 or plasmidmediated phosphoethanolamine transferases in general.

Original languageEnglish
Article numbere00580-17
JournalAntimicrobial agents and chemotherapy
Volume61
Issue number6
DOIs
Publication statusPublished - 01-06-2017

Fingerprint

Colistin
Lipopolysaccharides
Acinetobacter baumannii
Lipid A
Klebsiella pneumoniae
Pseudomonas aeruginosa
Escherichia coli
Transferases
Staphylococcal Pneumonia
Enterococcus faecium
Enterobacter
Klebsiella
Enterobacteriaceae
China
Mass Spectrometry
Plasmids
phosphorylethanolamine

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Liu, Y. Y., Chandler, C. E., Leung, L. M., McElheny, C. L., Mettus, R. T., Shanks, R. M. Q., ... Doi, Y. (2017). Structural modification of lipopolysaccharide conferred by mcr-1 in gram-negative ESKAPE pathogens. Antimicrobial agents and chemotherapy, 61(6), [e00580-17]. https://doi.org/10.1128/AAC.00580-17
Liu, Yi Yun ; Chandler, Courtney E. ; Leung, Lisa M. ; McElheny, Christi L. ; Mettus, Roberta T. ; Shanks, Robert M.Q. ; Liu, Jian Hua ; Goodlett, David R. ; Ernst, Robert K. ; Doi, Yohei. / Structural modification of lipopolysaccharide conferred by mcr-1 in gram-negative ESKAPE pathogens. In: Antimicrobial agents and chemotherapy. 2017 ; Vol. 61, No. 6.
@article{e6cd2c2a151e4d679d036dfa68a225c3,
title = "Structural modification of lipopolysaccharide conferred by mcr-1 in gram-negative ESKAPE pathogens",
abstract = "mcr-1 was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of Escherichia coli and Klebsiella pneumoniae in China and has subsequently been identified worldwide in various species of the family Enterobacteriaceae. mcr-1 encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-Acylated lipid A in E. coli. Here, we investigated the effects of mcr-1 on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens, which are often treated clinically by colistin. The effects of mcr-1 on colistin resistance were determined using MIC assays of laboratory and clinical strains of E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. Lipid A structural changes resulting from MCR-1 were analyzed by mass spectrometry. The introduction of mcr-1 led to colistin resistance in E. coli, K. pneumoniae, and A. baumannii but only moderately reduced susceptibility in P. aeruginosa. Phosphoethanolamine modification of lipid A was observed consistently for all four species. These findings highlight the risk of colistin resistance as a consequence of mcr-1 expression among ESKAPE pathogens, especially in K. pneumoniae and A. baumannii. Furthermore, the observation that lipid A structures were modified despite only modest increases in colistin MICs in some instances suggests more sophisticated surveillance methods may need to be developed to track the dissemination of mcr-1 or plasmidmediated phosphoethanolamine transferases in general.",
author = "Liu, {Yi Yun} and Chandler, {Courtney E.} and Leung, {Lisa M.} and McElheny, {Christi L.} and Mettus, {Roberta T.} and Shanks, {Robert M.Q.} and Liu, {Jian Hua} and Goodlett, {David R.} and Ernst, {Robert K.} and Yohei Doi",
year = "2017",
month = "6",
day = "1",
doi = "10.1128/AAC.00580-17",
language = "English",
volume = "61",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "6",

}

Liu, YY, Chandler, CE, Leung, LM, McElheny, CL, Mettus, RT, Shanks, RMQ, Liu, JH, Goodlett, DR, Ernst, RK & Doi, Y 2017, 'Structural modification of lipopolysaccharide conferred by mcr-1 in gram-negative ESKAPE pathogens', Antimicrobial agents and chemotherapy, vol. 61, no. 6, e00580-17. https://doi.org/10.1128/AAC.00580-17

Structural modification of lipopolysaccharide conferred by mcr-1 in gram-negative ESKAPE pathogens. / Liu, Yi Yun; Chandler, Courtney E.; Leung, Lisa M.; McElheny, Christi L.; Mettus, Roberta T.; Shanks, Robert M.Q.; Liu, Jian Hua; Goodlett, David R.; Ernst, Robert K.; Doi, Yohei.

In: Antimicrobial agents and chemotherapy, Vol. 61, No. 6, e00580-17, 01.06.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Structural modification of lipopolysaccharide conferred by mcr-1 in gram-negative ESKAPE pathogens

AU - Liu, Yi Yun

AU - Chandler, Courtney E.

AU - Leung, Lisa M.

AU - McElheny, Christi L.

AU - Mettus, Roberta T.

AU - Shanks, Robert M.Q.

AU - Liu, Jian Hua

AU - Goodlett, David R.

AU - Ernst, Robert K.

AU - Doi, Yohei

PY - 2017/6/1

Y1 - 2017/6/1

N2 - mcr-1 was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of Escherichia coli and Klebsiella pneumoniae in China and has subsequently been identified worldwide in various species of the family Enterobacteriaceae. mcr-1 encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-Acylated lipid A in E. coli. Here, we investigated the effects of mcr-1 on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens, which are often treated clinically by colistin. The effects of mcr-1 on colistin resistance were determined using MIC assays of laboratory and clinical strains of E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. Lipid A structural changes resulting from MCR-1 were analyzed by mass spectrometry. The introduction of mcr-1 led to colistin resistance in E. coli, K. pneumoniae, and A. baumannii but only moderately reduced susceptibility in P. aeruginosa. Phosphoethanolamine modification of lipid A was observed consistently for all four species. These findings highlight the risk of colistin resistance as a consequence of mcr-1 expression among ESKAPE pathogens, especially in K. pneumoniae and A. baumannii. Furthermore, the observation that lipid A structures were modified despite only modest increases in colistin MICs in some instances suggests more sophisticated surveillance methods may need to be developed to track the dissemination of mcr-1 or plasmidmediated phosphoethanolamine transferases in general.

AB - mcr-1 was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of Escherichia coli and Klebsiella pneumoniae in China and has subsequently been identified worldwide in various species of the family Enterobacteriaceae. mcr-1 encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-Acylated lipid A in E. coli. Here, we investigated the effects of mcr-1 on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens, which are often treated clinically by colistin. The effects of mcr-1 on colistin resistance were determined using MIC assays of laboratory and clinical strains of E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. Lipid A structural changes resulting from MCR-1 were analyzed by mass spectrometry. The introduction of mcr-1 led to colistin resistance in E. coli, K. pneumoniae, and A. baumannii but only moderately reduced susceptibility in P. aeruginosa. Phosphoethanolamine modification of lipid A was observed consistently for all four species. These findings highlight the risk of colistin resistance as a consequence of mcr-1 expression among ESKAPE pathogens, especially in K. pneumoniae and A. baumannii. Furthermore, the observation that lipid A structures were modified despite only modest increases in colistin MICs in some instances suggests more sophisticated surveillance methods may need to be developed to track the dissemination of mcr-1 or plasmidmediated phosphoethanolamine transferases in general.

UR - http://www.scopus.com/inward/record.url?scp=85019671091&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019671091&partnerID=8YFLogxK

U2 - 10.1128/AAC.00580-17

DO - 10.1128/AAC.00580-17

M3 - Article

C2 - 28373195

AN - SCOPUS:85019671091

VL - 61

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 6

M1 - e00580-17

ER -