title: The Effect of Colistin Resistance-Associated Mutations on the Fitness ofAcinetobacter baumannii.
abstract: Acinetobacter baumanniihad emerged as an important nosocomial and opportunistic pathogen worldwide. To assess the evolution of colistin resistance inA. baumanniiand its effect on bacterial fitness, we exposed five independent colonies ofA. baumanniiATCC 17978 to increasing concentrations of colistin in agar (4/5) and liquid media (1/5). Stable resistant isolates were analyzed using whole genome sequencing. All strains were colistin resistant after exposure to colistin. In addition to the previously reportedlpxCADandpmrABmutations, we identified four novel putative colistin resistance genes:A1S_1983. hepA. A1S_3026, andrsfS. Lipopolysaccharide (LPS) loss mutants exhibited higher fitness costs than those of thepmrBmutant in nutrient-rich medium. The colistin-resistant mutants had a higher inhibition ratio in the serum growth experiment than that of the wild type strain in 100% serum. Minimum inhibitory concentration (MIC) results showed that the LPS-deficient but not thepmrBmutant had an altered antibiotic resistance profile. The compensatory mutations partially or completely rescued the LPS-deficient's fitness, suggesting that compensatory mutations play an important role in the emergence and spread of colistin resistance inA. baumannii.
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Xinli
authors.initials: X
authors.lastname: Mu
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Nanfei
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Keren
authors.initials: K
authors.lastname: Shi
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang UniversityHangzhou, China; State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang UniversityHangzhou, China.
authors.forename: Yunsong
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University Hangzhou, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Hua
keywords: Acinetobacter baumannii; colistin; fitness cost; resistance mechanism; whole genome sequencing