title: Tigecycline resistance in Acinetobacter baumannii mediated by frameshift mutation in plsC, encoding 1-acyl-sn-glycerol-3-phosphate acyltransferase.
abstract: Acinetobacter baumannii is an important pathogen of healthcare-associated infections and shows multidrug resistance. With the increasing application of tigecycline, isolates resistant to this antibiotic are of growing concern clinically. However, the definitive mechanism of tigecycline resistance remains unclear. To explore the mechanism of tigecycline resistance in A. baumannii, a tigecycline-resistant strain was obtained by increasing the concentration of the antimicrobial in liquid culture. Three mutations were identified by the whole genome comparison, including one synonymous substitution in a hypothetical protein and a frameshift mutation in plsC and omp38. The plsC gene was confirmed to cause decreased susceptibility to tigecycline by a complementation experiment and cellular membrane change was detected by flow cytometry. By measuring the relative growth rate, the fitness cost of plsC was estimated to be approximately 8 %. In conclusion, plsC was found to play an important role in tigecycline resistance in A. baumannii. The minor fitness cost of plsC indicates a high risk of the emergence and development of tigecycline resistance in A. baumannii.
authors.affiliation: Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Ji
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Hua
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics*; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016368:Frameshift Mutation; D005816:Genetic Complementation Test; D016680:Genome, Bacterial; D006801:Humans; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D012641:Selection, Genetic; D012692:Serial Passage; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D008911:Minocycline