title: The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications.
abstract: 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.
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Thi Khanh Nhu
authors.affiliation: Department of Pathogen and Molecular Biology, London School of Hygiene &Tropical Medicine, London.
authors.forename: David W
authors.initials: DW
authors.lastname: Riordan
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Tran
authors.initials: T
authors.lastname: Do Hoang Nhu
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Duy Pham
authors.initials: DP
authors.lastname: Thanh
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, United Kingdom.
authors.forename: Guy
authors.initials: G
authors.lastname: Thwaites
authors.affiliation: The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Phu
authors.initials: NP
authors.lastname: Huong Lan
authors.affiliation: Department of Pathogen and Molecular Biology, London School of Hygiene &Tropical Medicine, London.
authors.forename: Brendan W
authors.initials: BW
authors.lastname: Wren
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Department of Pathogen and Molecular Biology, London School of Hygiene &Tropical Medicine, London.|Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
authors.affiliation: Department of Pathogen and Molecular Biology, London School of Hygiene &Tropical Medicine, London.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Stabler
mesh_terms: D040981:Acinetobacter baumannii / Q000235:genetics / Q000254:growth & development; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003091:Colistin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009154:Mutation; D014744:Vietnam
chemical_list: D001426:Bacterial Proteins; D003091:Colistin