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Detection of S83V GyrA mutation in quinolone-resistant Shewanella algae using comparative genomics
Journal of Microbiology, Immunology and Infection ( IF 4.5 ) Pub Date : 2020-05-23 , DOI: 10.1016/j.jmii.2020.04.019
Chien-Hao Tseng , Jan-Fang Cheng , Shi-Yu Chen , Wen-Huei Chen , Zhi-Yuan Shi , Yu-Hui Lin , Che-An Tsai , Shih-Ping Lin , Yung-Chun Chen , Yu-Chia Lin , Yao-Ting Huang , Po-Yu Liu

Background

Shewanella algae is a zoonotic pathogen that poses a serious health threat to immunocompromised hosts. Treatment of S. algae infections is challenging due to the pathogen's intrinsic resistance to a variety of β-lactam antibiotics. Therapeutic options have become further limited by the emergence of quinolone-resistant strains. Currently, there are few studies concerning the genetic and molecular mechanisms underlying acquired quinolones resistance in S. algae. qnrA was once proposed as the candidate gene related to quinolones resistance in S. algae. However, recent studies demonstrated qnrA are highly conservative and does not confer resistance to quinolones in S. algae.

Methods

A total of 27 non-duplicated isolates of S. algae strains were examined. MICs of ciprofloxacin were determined using Vitek 2. Whole genome sequencing was performed using MiSeq platform. Comprehensive Antibiotic Resistance Database and ResFinder were used for annotation of quinolones resistance genes. Multiple sequence alignment by EMBOSS Clustal Omega were used to identified mutation in quinolone resistance-determining regions. To investigation of the alteration of protein structure induced by mutation, in silico molecular docking studies was conducted using Accryl Discovery studio visualizer.

Results

All S. algae harbored the quinolone-resistance associated genes (qnrA, gyrA, gyrB, parC, and parE) regardless its resistance to ciprofloxacin. Comparison of these genomes identified a nonsynonymous mutation (S83V) in chromosome-encoded gyrase subunits (GyrA) in quinolone-resistant strain. We found this mutation disrupts the water-metal ion bridge, reduces the affinity of the quinolone-enzyme complex for the metal ions and therefore decrease the capability of quinolones to stabilize cleavage complexes.

Conclusions

The study provides insight into the quinolone resistance mechanisms in S. algae, which would be helpful for the evolution of antibiotic resistance in this bacterium.



中文翻译:

使用比较基因组学检测耐喹诺酮类希瓦氏藻中的 S83V GyrA 突变

背景

Shewanella 藻类是一种人畜共患病病原体,对免疫功能低下的宿主构成严重的健康威胁。S 的处理。由于病原体对各种 β-内酰胺抗生素具有内在抗性,因此藻类感染具有挑战性。喹诺酮耐药菌株的出现进一步限制了治疗选择。目前,关于藻类获得性喹诺酮类抗性的遗传和分子机制的研究很少。qnrA曾被提出作为S.藻类中喹诺酮类抗性相关的候选基因。然而,最近的研究表明qnrA是高度保守的,并且不会对喹诺酮类药物产生耐药性。S. 藻类

方法

检查了总共 27 个非重复的S.藻类菌株分离株。使用 Vitek 2 确定环丙沙星的 MIC。使用 MiSeq 平台进行全基因组测序。综合抗生素耐药数据库和ResFinder用于喹诺酮类耐药基因的注释。EMBOSS Clustal Omega 的多序列比对用于鉴定喹诺酮耐药性决定区域的突变。为了研究由突变引起的蛋白质结构的改变,使用 Accryl Discovery Studio 可视化器进行了计算机分子对接研究。

结果

所有S. 藻类都含有喹诺酮抗性相关基因(qnrAgyrAgyrBparCparE),而不管其对环丙沙星的抗性。这些基因组的比较确定了喹诺酮抗性菌株中染色体编码的促旋酶亚基 (GyrA) 中的非同义突变 (S83V)。我们发现这种突变破坏了水-金属离子桥,降低了喹诺酮-酶复合物对金属离子的亲和力,因此降低了喹诺酮类稳定裂解复合物的能力。

结论

该研究提供了对S 中喹诺酮类耐药机制的深入了解。藻类,这将有助于这种细菌的抗生素耐药性的进化。

更新日期:2020-05-23
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