Characterization and Molecular Mechanism of Aminoglycoside-6-Adenyl Transferase Associated with Aminoglycoside Resistance from Elizabethkingia meningoseptica

作者：Shaoxing Zhang, Yuxin Zhang, Ruijie Liu, Shuying Yuan, Yanwen Chen, Wenjie Li, Xinrong Lu, Yongliang Tong, Linlin Hou, Li Chen, Guiqin Sun · 发表于：Infection and Drug Resistance · 年份：2023 · DOI：10.2147/idr.s423418 · 被引用次数：5 · 研究领域：Infections and bacterial resistance、Antibiotic Resistance in Bacteria、Plant Pathogenic Bacteria Studies

Purpose: Elizabethkingia meningoseptica (EM) is a multi-drug-resistant bacterium of global concern for its role in nosocomial infection and is generally resistant to aminoglycoside antibiotics. In the whole genome of an EM strain (FMS-007), an aminoglycoside-6-adenyl transferase gene ( ant(6)FMS-007 ) was predicted. This study aimed to characterize the biochemical function of ANT(6) FMS-007 and analyze the relationship between genotype and phenotype of ant(6) in clinical EM isolates, so as to provide evidence for clinical precision drug use. This study could establish a method for the verification of known or unknown functionally resistant genes. Methods: A total of 42 EM clinical isolates were collected from clinical departments during 2015– 2023. The phenotype of aminoglycoside antibiotics was analyzed by broth microdilution (BMD) and Kirby-Bauer (K-B) methods. The whole-length ant(6) from EM clinical isolates was analyzed by polymerase chain reaction (PCR) and sequencing. The biochemical function of predictive ANT(6) FMS-007 from the FMS-007 whole genome was identified by 3D plate experiment and mass spectrometry analysis. Candidate active sites were predicted by multi-species sequence alignment and molecular docking, and other important sites were identified in the comparison of ant(6) genotypes and phenotypes of EM clinical isolates. Drug susceptibility test was used to verify the function of these sites. Results: The predictive ANT(6) FMS-007 protein could inactivate ST...