Methicillin-resistant Staphylococcus aureus (MRSA) causes severe infections and poses a global healthcare challenge. The utilization of novel molecules which confer synergistical effects to existing MRSA-directed antibiotics is one of the well-accepted strategies in lieu of de novo development of new antibiotics. Thymol is a key component of the essential oil of plants in the Thymus and Origanum genera. Despite the absence of antimicrobial potency, thymol is known to inhibit MRSA biofilm formation. However, the anti-MRSA activity of thymol analogs is not well characterized. Here, we assessed the antimicrobial activity of several thymol derivatives and found that 4-chloro-2-isopropyl-5-methylphenol (chlorothymol) has antimicrobial activity against MRSA and in addition it also prevents biofilm formation. Chlorothymol inhibited staphyloxanthin production, slowed MRSA motility, and altered bacterial cell density and size. This compound also showed a synergistic antimicrobial activity with oxacillin against highly resistant S. aureus clinical isolates and biofilms associated with these isolates. Our results demonstrate that chlorinated thymol derivatives should be considered as a new lead compound in anti-MRSA therapeutics.

中文翻译：

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4-Chloro-2-Isopropyl-5-Methylphenol 对耐甲氧西林金黄色葡萄球菌具有抗菌和辅助活性。

耐甲氧西林金黄色葡萄球菌(MRSA) 会引起严重感染，并对全球医疗保健构成挑战。利用赋予现有 MRSA 定向抗生素协同作用的新型分子是代替从头开发新抗生素的广为接受的策略之一。百里酚是百里香和牛至属植物精油的关键成分。尽管缺乏抗菌效力，但已知百里酚可抑制 MRSA 生物膜的形成。然而，百里酚类似物的抗 MRSA 活性尚未得到很好的表征。在这里，我们评估了几种百里酚衍生物的抗菌活性，发现 4-chloro-2-isopropyl-5-methylphenol (chlorothymol) 对 MRSA 具有抗菌活性，此外它还可以防止生物膜形成。氯百里酚抑制葡萄黄素的产生，减缓 MRSA 的运动，并改变了细菌细胞的密度和大小。该化合物还显示出与苯唑西林对高度耐药的协同抗菌活性金黄色葡萄球菌临床分离株和与这些分离株相关的生物膜。我们的结果表明，氯化百里酚衍生物应被视为抗 MRSA 治疗的新先导化合物。