Profiling of omadacycline resistance in clinical MRSA: A nationwide genomic survey and in vitro evolutionary analysis.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Profiling of omadacycline resistance in clinical MRSA: A nationwide genomic survey and in vitro evolutionary analysis.
Συγγραφείς: Chen Y; Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China., Hong Y; Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Wang X; School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang, China., Cheng X; Hangzhou normal university, Hangzhou, Zhejiang, China., Zhu F; Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Wang H; Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Wang Z; Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Jiang S; Centre of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China., Chen M; Hangzhou Center for Disease Control and Prevention, Hangzhou, Zhejiang, China., Zhuang H; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Liu Y; Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Chen Y; Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China. Electronic address: chenyan@zju.edu.cn., Sun L; Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China. Electronic address: lusun@zju.edu.cn., Yu Y; Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. Electronic address: yvys119@zju.edu.cn.
Πηγή: International journal of antimicrobial agents [Int J Antimicrob Agents] 2025 Jul; Vol. 66 (1), pp. 107499. Date of Electronic Publication: 2025 Apr 01.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 9111860 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7913 (Electronic) Linking ISSN: 09248579 NLM ISO Abbreviation: Int J Antimicrob Agents Subsets: MEDLINE
Imprint Name(s): Original Publication: Amsterdam : Elsevier Science Publishers, c1991-
Ιατρικοί όροι (MeSH): Methicillin-Resistant Staphylococcus aureus*/drug effects , Methicillin-Resistant Staphylococcus aureus*/genetics , Methicillin-Resistant Staphylococcus aureus*/isolation & purification , Anti-Bacterial Agents*/pharmacology , Tetracyclines*/pharmacology , Drug Resistance, Bacterial*/genetics, Staphylococcal Infections/microbiology ; Ribosomal Proteins/genetics ; Bacterial Proteins/genetics ; Microbial Sensitivity Tests ; Humans ; Mutation ; Ribosomal Protein L3
Περίληψη: Objective: We aimed to evaluate the susceptibility of various clinical methicillin-resistant Staphylococcus aureus (MRSA) lineages to omadacycline and investigate the mechanisms underlying omadacycline resistance.
Methods: Omadacycline MICs for all MRSA isolates were determined via broth dilution. Representative clinical MRSA isolates of ST59, ST5 and ST9 were exposed to increasing concentrations of omadacycline. Mutants developing omadacycline resistance were isolated, sequenced, and compared using breseq. Molecular cloning was employed to elucidate the mechanisms of omadacycline resistance.
Results: Omadacycline MICs against MRSA ranged from 0.06 to 8 mg/L, with MIC50 and MIC90 values at 0.25 and 4 mg/L, respectively, and an overall resistance rate of 13%. All CC59 isolates were susceptible to omadacycline. Resistant isolates were mainly concentrated in HA-MRSA clones CC5. All 47 isolates with MICs ≥4 mg/L harbored tet(M) and the rpsJ K57M mutation. Cloning experiments demonstrated that both tet(M) and mutated rpsJ reduced susceptibility to omadacycline. The rpsJ gene was a common target in different MRSA lineages for decreased omadacycline susceptibility. Continuous exposure to omadacycline induced novel mutations in rpsJ (H56Y in ST9; H56R, K57M in ST59; and K57M, H56Y in ST5), which cloning experiments confirmed could variably reduce omadacycline susceptibility. Furthermore, mutated mepA also contributed to reduced omadacycline susceptibility.
Conclusion: Susceptibility to omadacycline varied among different MRSA lineages, while some CC5 isolates exhibiting the resistance phenotype. The rpsJ gene serves as a general target for the evolution of omadacycline resistance and plays an important role in the refinement of future tetracycline derivatives.
(Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Contributed Indexing: Keywords: MRSA; Omadacycline; Resistance; rpsJ. tet(M)
Substance Nomenclature: 0 (Anti-Bacterial Agents)
090IP5RV8F (omadacycline)
0 (Tetracyclines)
0 (Ribosomal Proteins)
0 (Bacterial Proteins)
0 (RPL3 protein, human)
0 (Ribosomal Protein L3)
Entry Date(s): Date Created: 20250403 Date Completed: 20250509 Latest Revision: 20260127
Update Code: 20260130
DOI: 10.1016/j.ijantimicag.2025.107499
PMID: 40180147
Βάση Δεδομένων: MEDLINE