smeRv突变使嗜麦芽窄养单胞菌对一线抗生素甲氧苄氨苄/磺胺甲恶唑和左氧氟沙星耐药。

IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES
Nuchjaree Boonyong, Nisanart Charoenlap, Parinya Tipanyo, Pitthawat Grittanaanun, Skorn Mongkolsuk, Paiboon Vattanaviboon
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引用次数: 0

摘要

背景:嗜麦芽窄养单胞菌是世界范围内医院获得性感染的常见病原体之一。嗜麦芽葡萄球菌感染的主要问题是其对多种抗生素的极端耐药性。方法:采用连续传代技术筛选嗜麦芽链球菌K279a耐恩诺沙星突变体。结果:本研究发现,从嗜麦芽链球菌K279a中筛选出的对兽药恩诺沙星耐药的突变株KE507对甲氧苄啶/磺胺甲恶唑(复方新诺明)、左氧氟沙星和米诺环素具有耐药性,符合临床与实验室标准协会的指南。这些抗生素是常规用于治疗嗜麦芽葡萄球菌感染的一线药物。KE507突变体对所有喹诺酮类药物、阿奇霉素和新霉素的耐药性也增加。利用全基因组测序、抗生素耐药基因表达谱和突变分析进行的分子表征表明,SmeRv (Q208insHSPRFTW)失活有助于对喹诺酮类药物(包括左氧氟沙星)、共新诺明和部分新霉素产生耐药性,但对阿奇霉素或米诺环素没有耐药性。SmeRv是SmeVWX多药外排泵的转录调节因子。这些数据以及硅结构分析表明,SmeRv的突变导致SmeRv结构的构象变化,从而导致SmeVWX外排转运体表达的激活,并随后对共新诺明和喹诺酮类抗生素产生耐药性。结论:S。因此,嗜麦芽菌可以通过SmeRv突变获得对主要用于治疗嗜麦芽菌感染的抗生素的耐药性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mutation of smeRv Renders Stenotrophomonas maltophilia Resistant to First-Line Antibiotics Trimethoprim/Sulfamethoxazole and Levofloxacin.

Background:Stenotrophomonas maltophilia is one of the common causative agents of hospital-acquired infections worldwide. The major concern regarding S. maltophilia infections is its extreme resistance to multiple antibiotics. Methods: Enrofloxacin-resistant mutants of S. maltophilia K279a were selected using a serial passage technique. Results: In this study, we showed that one of the mutant strains, KE507, which was selected from S. maltophilia K279a for its resistance to the veterinary drug enrofloxacin, conferred resistance to trimethoprim/sulfamethoxazole (co-trimoxazole), levofloxacin, and minocycline as per the Clinical and Laboratory Standards Institute guideline. These antibiotics are the first-line drugs routinely used to treat S. maltophilia infections. The KE507 mutant also showed increased resistance to all tested quinolones, azithromycin, and neomycin. Molecular characterization using whole genome sequencing, antibiotic resistance gene expression profiles, and mutational analysis indicated that inactivation of SmeRv (Q208insHSPRFTW), a transcriptional regulator of the SmeVWX multidrug efflux pump, contributes to resistance to quinolones (including levofloxacin), co-trimoxazole, and partially to neomycin, but not to azithromycin or minocycline. These data, together with in silico structural analysis, suggest that the mutation of SmeRv causes a conformational change in the SmeRv structure, which leads to the activation of SmeVWX efflux transporter expression and subsequent resistance to co-trimoxazole and quinolone antibiotics. Conclusion:S. maltophilia can thus acquire resistance to the antibiotics primarily used to treat S. maltophilia infections through the mutation of SmeRv.

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来源期刊
Antibiotics-Basel
Antibiotics-Basel Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
7.30
自引率
14.60%
发文量
1547
审稿时长
11 weeks
期刊介绍: Antibiotics (ISSN 2079-6382) is an open access, peer reviewed journal on all aspects of antibiotics. Antibiotics is a multi-disciplinary journal encompassing the general fields of biochemistry, chemistry, genetics, microbiology and pharmacology. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on the length of papers.
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