Boonyong Nuchjaree, Charoenlap Nisanart, Tipanyo Parinya, Grittanaanun Pitthawat, Mongkolsuk Skorn, Vattanaviboon Paiboon
Program in Applied Biological Science-Environmental Health, Chulabhorn Graduate Institute, Bangkok 10210, Thailand.
Laboratory of Biotechnology, Chulabhorn Research Institute, Bangkok 10210, Thailand.
Antibiotics (Basel). 2025 May 28;14(6):550. doi: 10.3390/antibiotics14060550.
is one of the common causative agents of hospital-acquired infections worldwide. The major concern regarding infections is its extreme resistance to multiple antibiotics. Enrofloxacin-resistant mutants of K279a were selected using a serial passage technique. In this study, we showed that one of the mutant strains, KE507, which was selected from 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 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. can thus acquire resistance to the antibiotics primarily used to treat infections through the mutation of SmeRv.
是全球医院获得性感染的常见病原体之一。关于感染的主要担忧是其对多种抗生素具有极强的耐药性。使用连续传代技术筛选出了对恩诺沙星耐药的K279a突变体。在本研究中，我们发现其中一个突变菌株KE507，它是从K279a中筛选出来的，对兽药恩诺沙星具有耐药性，根据临床和实验室标准协会的指南，它对甲氧苄啶/磺胺甲恶唑（复方新诺明）、左氧氟沙星和米诺环素也具有耐药性。这些抗生素是常规用于治疗感染的一线药物。KE507突变体对所有测试的喹诺酮类药物、阿奇霉素和新霉素的耐药性也有所增加。使用全基因组测序、抗生素抗性基因表达谱和突变分析进行的分子特征分析表明，SmeVWX多药外排泵的转录调节因子SmeRv（Q208insHSPRFTW）失活导致对喹诺酮类药物（包括左氧氟沙星）、复方新诺明以及部分对新霉素产生耐药性，但对阿奇霉素或米诺环素没有耐药性。这些数据与计算机模拟结构分析一起表明，SmeRv的突变导致其结构发生构象变化，从而导致SmeVWX外排转运蛋白表达激活以及随后对复方新诺明和喹诺酮类抗生素产生耐药性。因此可以通过SmeRv的突变获得对主要用于治疗感染的抗生素的耐药性。
