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Characterization of blaOXA-542-mediated carbapenem resistance in Acinetobacter baumannii

鲍曼不动杆菌 碳青霉烯 生物 美罗培南 微生物学 肉汤微量稀释 头孢菌素 抗生素耐药性 不动杆菌 抗菌剂 遗传学 抗生素 最小抑制浓度 细菌 铜绿假单胞菌
作者
Jingchen Hao,Feng Lü,Ping Chen,Chengjie Ji,Na Li,Yue Xu,Yuan Chen,Cuicui Liu,Jian Hu,Guocai Li
出处
期刊:Journal of Antimicrobial Chemotherapy [Oxford University Press]
卷期号:80 (10): 2854-2861
标识
DOI:10.1093/jac/dkaf311
摘要

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) causes multiple anatomical site infections, representing a significant public health threat. Aim This study reports the isolation and characterization of a carbapenem-resistant A. baumannii harbouring blaOXA-542, followed by a comprehensive investigation of its antimicrobial resistance mechanisms and genomic characteristics. Methods Firstly, antimicrobial susceptibility testing was performed using the broth microdilution method. Subsequently, whole-genome sequencing was employed to identify and characterize the resistance and virulence determinants. The functional validation of resistance mechanisms was performed by gene knockdown and construction of expression vectors. The fitness cost of β-lactamase expression was identified by a bacterial growth kinetic test. Molecular docking was utilized to predict potential binding sites of β-lactamase and carbapenems. Finally, the genetic characteristics of the isolates were analysed through comparative genomics analyses and phylogenetic tree construction. Results and conclusions The results demonstrated that blaOXA-542 confers resistance to carbapenem and penicillin in A. baumannii and Escherichia coli while exhibiting no significant impact on cephalosporins. The ability of blaOXA-542 to hydrolyze meropenem was further confirmed by modified carbapenem inactivation assay (mCIM). Expression of blaOXA-542 in E. coli BL21 showed no significant growth rate alteration. Comparative analysis of the blaOXA-542 genetic environment revealed a close association with Acinetobacter pitti. This study reports the emergence of blaOXA-542-mediated carbapenem and penicillin resistance in a novel A. baumannii lineage (ST2795Pas/ST3464Oxf), highlighting the urgent need for rational antibiotic use against specific pathogens.
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