Cargando…
Identification and characterization of a novel 6′-N-aminoglycoside acetyltransferase AAC(6′)-Va from a clinical isolate of Aeromonas hydrophila
BACKGROUND: Aeromonas 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 wa...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619662/ https://www.ncbi.nlm.nih.gov/pubmed/37920263 http://dx.doi.org/10.3389/fmicb.2023.1229593 |
_version_ | 1785130034588024832 |
---|---|
author | Zhang, Guozhi Zhang, Lei Sha, Yuning Chen, Qiaoying Lin, Naru Zhao, Jingxuan Zhang, Yuan Ji, Yongan Jiang, Weiyan Zhang, Xueya Li, Qiaoling Lu, Junwan Lin, Xi Li, Kewei Zhang, Hailin Bao, Qiyu Lu, Jun Hu, Yunliang Zhu, Tingting |
author_facet | Zhang, Guozhi Zhang, Lei Sha, Yuning Chen, Qiaoying Lin, Naru Zhao, Jingxuan Zhang, Yuan Ji, Yongan Jiang, Weiyan Zhang, Xueya Li, Qiaoling Lu, Junwan Lin, Xi Li, Kewei Zhang, Hailin Bao, Qiyu Lu, Jun Hu, Yunliang Zhu, Tingting |
author_sort | Zhang, Guozhi |
collection | PubMed |
description | BACKGROUND: Aeromonas 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. METHODS: The 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. RESULTS: The 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 [k(cat)/K(m) ratio = (3.35 ± 0.17) × 10(4) 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. CONCLUSION: The 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. |
format | Online Article Text |
id | pubmed-10619662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106196622023-11-02 Identification and characterization of a novel 6′-N-aminoglycoside acetyltransferase AAC(6′)-Va from a clinical isolate of Aeromonas hydrophila Zhang, Guozhi Zhang, Lei Sha, Yuning Chen, Qiaoying Lin, Naru Zhao, Jingxuan Zhang, Yuan Ji, Yongan Jiang, Weiyan Zhang, Xueya Li, Qiaoling Lu, Junwan Lin, Xi Li, Kewei Zhang, Hailin Bao, Qiyu Lu, Jun Hu, Yunliang Zhu, Tingting Front Microbiol Microbiology BACKGROUND: Aeromonas 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. METHODS: The 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. RESULTS: The 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 [k(cat)/K(m) ratio = (3.35 ± 0.17) × 10(4) 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. CONCLUSION: The 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. Frontiers Media S.A. 2023-10-18 /pmc/articles/PMC10619662/ /pubmed/37920263 http://dx.doi.org/10.3389/fmicb.2023.1229593 Text en Copyright © 2023 Zhang, Zhang, Sha, Chen, Lin, Zhao, Zhang, Ji, Jiang, Zhang, Li, Lu, Lin, Li, Zhang, Bao, Lu, Hu and Zhu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Zhang, Guozhi Zhang, Lei Sha, Yuning Chen, Qiaoying Lin, Naru Zhao, Jingxuan Zhang, Yuan Ji, Yongan Jiang, Weiyan Zhang, Xueya Li, Qiaoling Lu, Junwan Lin, Xi Li, Kewei Zhang, Hailin Bao, Qiyu Lu, Jun Hu, Yunliang Zhu, Tingting Identification and characterization of a novel 6′-N-aminoglycoside acetyltransferase AAC(6′)-Va from a clinical isolate of Aeromonas hydrophila |
title | Identification and characterization of a novel 6′-N-aminoglycoside acetyltransferase AAC(6′)-Va from a clinical isolate of Aeromonas hydrophila |
title_full | Identification and characterization of a novel 6′-N-aminoglycoside acetyltransferase AAC(6′)-Va from a clinical isolate of Aeromonas hydrophila |
title_fullStr | Identification and characterization of a novel 6′-N-aminoglycoside acetyltransferase AAC(6′)-Va from a clinical isolate of Aeromonas hydrophila |
title_full_unstemmed | Identification and characterization of a novel 6′-N-aminoglycoside acetyltransferase AAC(6′)-Va from a clinical isolate of Aeromonas hydrophila |
title_short | Identification and characterization of a novel 6′-N-aminoglycoside acetyltransferase AAC(6′)-Va from a clinical isolate of Aeromonas hydrophila |
title_sort | identification and characterization of a novel 6′-n-aminoglycoside acetyltransferase aac(6′)-va from a clinical isolate of aeromonas hydrophila |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619662/ https://www.ncbi.nlm.nih.gov/pubmed/37920263 http://dx.doi.org/10.3389/fmicb.2023.1229593 |
work_keys_str_mv | AT zhangguozhi identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT zhanglei identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT shayuning identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT chenqiaoying identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT linnaru identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT zhaojingxuan identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT zhangyuan identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT jiyongan identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT jiangweiyan identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT zhangxueya identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT liqiaoling identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT lujunwan identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT linxi identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT likewei identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT zhanghailin identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT baoqiyu identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT lujun identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT huyunliang identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila AT zhutingting identificationandcharacterizationofanovel6naminoglycosideacetyltransferaseaac6vafromaclinicalisolateofaeromonashydrophila |