title: Rapid emergence of high-level tigecycline resistance in Escherichia coli strains harbouring blaNDM-5 in vivo.
abstract: Tigecycline (TIG) resistance is a growing concern because this antibiotic is regarded as one of the last resorts to treat infections caused by multidrug-resistant and extensively drug-resistant (XDR) bacteria. Information regarding TIG-resistant Escherichia coli isolates is scarce. In this study, we report the emergence of high-level TIG resistance in a longitudinal series of XDR E. coli isolates collected during TIG treatment. Whole-genome sequencing was performed for six E. coli strains harbouring bla(NDM-5) and genomic comparison revealed two amino acid substitutions. Mutation in rpsJ could be a significant factor conferring TIG resistance in these isolates. The fitness cost of TIG resistance in resistant strains was evaluated by determining the relative growth rate, indicating that TIG resistance reduced fitness by ca. 7%. This study is the first report to demonstrate high-level TIG resistance in E. coli in vivo. In addition, we report the first treatment-emergent minimum inhibitory concentration (MIC) development of TIG from 1mg/L to 64 mg/L in E. coli. Clinicians should be aware of the risk of an increase in the MIC of TIG under therapy.
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, 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, Zhejiang 310016, 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, Zhejiang 310016, China.
authors.forename: Yunxing
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Hua
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, 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, Zhejiang 310016, China.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ruan
authors.affiliation: Department of Respiratory Medicine, Hangzhou Red Cross Hospital, Hangzhou 310003, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China. Electronic address: yvys119@163.com.
authors.forename: Yunsong
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D008137:Longitudinal Studies; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D000078304:Tigecycline; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D001618:beta-Lactamases; C552864:beta-lactamase NDM-1; D008911:Minocycline
keywords: Efflux pumps; Escherichia coli; Fitness cost; Tigecycline resistance