Staphylococcus aureus is an opportunistic pathogen that has the ability to cause a wide range of diseases including superficial infection and severe invasive life threatening infections. The pathogenicity of S. aureus is mediated by a group of virulence factors that mediate the colonization and penetration. The antibiotic resistance of S. aureus has evolved due to the abuse of antibiotics rendering the cure of infection very difficult especially with the shortage in new antibiotic production. To combat this shortage, repurposing of FDA-approved drugs against the virulence factors is a new strategy. The analgesic drug Diclofenac was found to have anti-virulence activity against Pseudomonas aeruginosa and Proteus mirabilis. This study aimed to demonstrate the anti-virulence effect of diclofenac against clinical MRSA isolates phenotypically and genotypically using qRT-PCR. In this study, diclofenac showed significant reduction in biofilm formation when compared to controls, the inhibition ranged between 22.67% and 70%. Also, remarkable inhibition of hemolysin activity was found (5.4–66.34%). Additionally, diclofenac has inhibitory activity against the staphyloxanthin production (8–57.2%). The results were confirmed by qRT-PCR that showed significant down-regulation of tested virulence genes. The down-regulation ranged from 43 to 64.05% for SarA, 36.85–64.75% for AgrA, 50–63.2% for hla, 38.55–60.35% for FnbA, 46.75–61.05% for IcaA, 27.55–64% for SigB and 51.05–72.8% for CrtM. In conclusion, diclofenac can be used in combination with antibiotics as anti-virulence agent against MDR-MRSA which will enhance the ability of immune system to eradicate infection.

中文翻译：

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双氯芬酸减轻耐多药金黄色葡萄球菌的毒力

金黄色葡萄球菌是一种机会性病原体，能够引起多种疾病，包括浅表感染和严重的危及生命的侵入性感染。金黄色葡萄球菌的致病性是由一组介导定植和渗透的毒力因子介导的。金黄色葡萄球菌的抗生素耐药性由于滥用抗生素而演变，使得感染的治愈变得非常困难，尤其是在新抗生素生产短缺的情况下。为了解决这种短缺，重新利用 FDA 批准的药物来对抗毒力因素是一种新策略。发现镇痛药双氯芬酸对铜绿假单胞菌和奇异变形杆菌具有抗毒力活性。本研究旨在使用 qRT-PCR 从表型和基因型上证明双氯芬酸对临床 MRSA 分离株的抗毒力作用。在这项研究中，与对照相比，双氯芬酸显示生物膜形成显着减少，抑制范围在 22.67% 和 70% 之间。此外，还发现对溶血素活性的显着抑制（5.4-66.34%）。此外，双氯芬酸对葡萄球菌黄素的产生具有抑制活性 (8–57.2%)。结果通过 qRT-PCR 得到证实，qRT-PCR 显示测试的毒力基因显着下调。SarA 的下调幅度为 43-64.05%，AgrA 为 36.85-64.75%，hla 为 50-63.2%，FnbA 为 38.55-60.35%，IcaA 为 46.75-61.05%，ScaA 为 24-515%。 CrtM 为 72.8%。综上所述，