The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications

Acinetobacter baumannii is a significant cause of opportunistic hospital acquired infection and has been identified as an important emerging infection due to its high levels of antimicrobial resistance. Multidrug resistant A. baumannii has risen rapidly in Vietnam, where colistin is becoming the dru...

Full description

Bibliographic Details
Main Authors: Thi Khanh Nhu, Nguyen, Riordan, David W., Do Hoang Nhu, Tran, Thanh, Duy Pham, Thwaites, Guy, Huong Lan, Nguyen Phu, Wren, Brendan W., Baker, Stephen, Stabler, Richard A
Format: Online
Language:English
Published: Nature Publishing Group 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916428/
id pubmed-4916428
recordtype oai_dc
spelling pubmed-49164282016-06-27 The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications Thi Khanh Nhu, Nguyen Riordan, David W. Do Hoang Nhu, Tran Thanh, Duy Pham Thwaites, Guy Huong Lan, Nguyen Phu Wren, Brendan W. Baker, Stephen Stabler, Richard A Article Acinetobacter baumannii is a significant cause of opportunistic hospital acquired infection and has been identified as an important emerging infection due to its high levels of antimicrobial resistance. Multidrug resistant A. baumannii has risen rapidly in Vietnam, where colistin is becoming the drug of last resort for many infections. In this study we generated spontaneous colistin resistant progeny (up to >256 μg/μl) from four colistin susceptible Vietnamese isolates and one susceptible reference strain (MIC <1.5 μg/μl). Whole genome sequencing was used to identify single nucleotide mutations that could be attributed to the reduced colistin susceptibility. We identified six lpxACD and three pmrB mutations, the majority of which were novel. In addition, we identified further mutations in six A. baumannii genes (vacJ, pldA, ttg2C, pheS and conserved hypothetical protein) that we hypothesise have a role in reduced colistin susceptibility. This study has identified additional mutations that may be associated with colistin resistance through novel resistance mechanisms. Our work further demonstrates how rapidly A. baumannii can generate resistance to a last resort antimicrobial and highlights the need for improved surveillance to identified A. baumannii with an extensive drug resistance profile. Nature Publishing Group 2016-06-22 /pmc/articles/PMC4916428/ /pubmed/27329501 http://dx.doi.org/10.1038/srep28291 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Thi Khanh Nhu, Nguyen
Riordan, David W.
Do Hoang Nhu, Tran
Thanh, Duy Pham
Thwaites, Guy
Huong Lan, Nguyen Phu
Wren, Brendan W.
Baker, Stephen
Stabler, Richard A
spellingShingle Thi Khanh Nhu, Nguyen
Riordan, David W.
Do Hoang Nhu, Tran
Thanh, Duy Pham
Thwaites, Guy
Huong Lan, Nguyen Phu
Wren, Brendan W.
Baker, Stephen
Stabler, Richard A
The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications
author_facet Thi Khanh Nhu, Nguyen
Riordan, David W.
Do Hoang Nhu, Tran
Thanh, Duy Pham
Thwaites, Guy
Huong Lan, Nguyen Phu
Wren, Brendan W.
Baker, Stephen
Stabler, Richard A
author_sort Thi Khanh Nhu, Nguyen
title The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications
title_short The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications
title_full The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications
title_fullStr The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications
title_full_unstemmed The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications
title_sort induction and identification of novel colistin resistance mutations in acinetobacter baumannii and their implications
description Acinetobacter baumannii is a significant cause of opportunistic hospital acquired infection and has been identified as an important emerging infection due to its high levels of antimicrobial resistance. Multidrug resistant A. baumannii has risen rapidly in Vietnam, where colistin is becoming the drug of last resort for many infections. In this study we generated spontaneous colistin resistant progeny (up to >256 μg/μl) from four colistin susceptible Vietnamese isolates and one susceptible reference strain (MIC <1.5 μg/μl). Whole genome sequencing was used to identify single nucleotide mutations that could be attributed to the reduced colistin susceptibility. We identified six lpxACD and three pmrB mutations, the majority of which were novel. In addition, we identified further mutations in six A. baumannii genes (vacJ, pldA, ttg2C, pheS and conserved hypothetical protein) that we hypothesise have a role in reduced colistin susceptibility. This study has identified additional mutations that may be associated with colistin resistance through novel resistance mechanisms. Our work further demonstrates how rapidly A. baumannii can generate resistance to a last resort antimicrobial and highlights the need for improved surveillance to identified A. baumannii with an extensive drug resistance profile.
publisher Nature Publishing Group
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916428/
_version_ 1613597976384503808