Identification and characterization of a novel 6′-N-aminoglycoside acetyltransferase AAC(6′)-Va from a clinical isolate of Aeromonas hydrophila

Frontiers in Microbiology

Microbiology

Jun Lu¹  Kewei Li²  Yuan Zhang²  Naru Lin²  Yuning Sha²  Xi Lin²  Jingxuan Zhao²  Lei Zhang³  Junwan Lu⁴  Weiyan Jiang⁵  Hailin Zhang⁵  Xueya Zhang⁵  Qiaoying Chen⁵  Yongan Ji⁵  Yunliang Hu⁵  Qiaoling Li⁵  Tingting Zhu⁵  Guozhi Zhang⁶  Qiyu Bao⁷ 

[1]Department of Clinical Laboratory, Quzhou People’s Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China

[2]Key Laboratory of Medical Genetics of Zhejiang Province, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China

[3]Key Laboratory of Medical Genetics of Zhejiang Province, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China

[4]Department of Clinical Laboratory, Quzhou People’s Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China

[5]Medical Molecular Biology Laboratory, School of Medicine, Jinhua Polytechnic, Jinhua, China

[6]The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, China

[7]The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, China

[8]Key Laboratory of Medical Genetics of Zhejiang Province, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China

[9]The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, China

[10]Key Laboratory of Medical Genetics of Zhejiang Province, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China

[11]Medical Molecular Biology Laboratory, School of Medicine, Jinhua Polytechnic, Jinhua, China

关键词: AAC(6′)-Va;    aminoglycoside resistance;    aminoglycoside-modifying enzyme;    aminoglycoside 6′-acetyltransferase;    Aeromonas hydrophila;   

DOI  :  10.3389/fmicb.2023.1229593

 received in 2023-05-26, accepted in 2023-10-02,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundAeromonas species have been identified as agents responsible for various diseases in both humans and animals. Multidrug-resistant Aeromonas strains pose a significant public health threat due to their emergence and spread in clinical settings and the environment. The aim of this study was to determine a novel resistance mechanism against aminoglycoside antimicrobials in a clinical isolate.MethodsThe function of aac(6′)-Va was verified by gene cloning and antibiotic susceptibility tests. To explore the in vivo activity of the enzyme, recombinant proteins were expressed, and enzyme kinetics were tested. To determine the molecular background and mechanism of aac(6′)-Va, whole-genome sequencing and bioinformatic analysis were performed.ResultsThe novel aminoglycoside N-acetyltransferase gene aac(6′)-Va confers resistance to several aminoglycosides. Among the antimicrobials tested, ribostamycin showed the highest increase (128-fold) in the minimum inhibitory concentration (MIC) compared with the control strains. According to the MIC results of the cloned aac(6′)-Va, AAC(6′)-Va also showed the highest catalytic efficiency for ribostamycin [kcat/Km ratio = (3.35 ± 0.17) × 104 M−1 s−1]. Sharing the highest amino acid identity of 54.68% with AAC(6′)-VaIc, the novel aminoglycoside N-acetyltransferase constituted a new branch of the AAC(6′) family due to its different resistance profiles. The gene context of aac(6′)-Va and its close relatives was conserved in the genomes of species of the genus Aeromonas.ConclusionThe novel resistance gene aac(6′)-Va confers resistance to several aminoglycosides, especially ribostamycin. Our finding of a novel resistance gene in clinical A. hydrophila will help us develop more effective treatments for this pathogen’s infections.

【 授权许可】

Unknown   
Copyright © 2023 Zhang, Zhang, Sha, Chen, Lin, Zhao, Zhang, Ji, Jiang, Zhang, Li, Lu, Lin, Li, Zhang, Bao, Lu, Hu and Zhu.