Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Arch Microbiol. 2020 Dec;202(10):2751-2760. doi: 10.1007/s00203-020-01992-y. Epub 2020 Jul 31.
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.
金黄色葡萄球菌是一种机会性病原体，能够引起广泛的疾病，包括浅表感染和严重的侵袭性生命威胁感染。金黄色葡萄球菌的致病性是由一组毒力因子介导的，这些因子介导了定植和穿透。由于抗生素的滥用，金黄色葡萄球菌的抗生素耐药性已经进化，使得感染的治疗变得非常困难，尤其是新抗生素的生产短缺。为了应对这种短缺，重新利用 FDA 批准的药物来对抗毒力因子是一种新的策略。研究发现，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。本研究旨在通过 qRT-PCR 从表型和基因型上证明双氯芬酸对临床耐甲氧西林金黄色葡萄球菌 (MRSA) 分离株的抗毒力作用。在这项研究中，与对照组相比，双氯芬酸显著减少了生物膜的形成，抑制率在 22.67%至 70%之间。此外，还发现溶血素活性有显著抑制（5.4-66.34%）。此外，双氯芬酸对金黄色素的产生有抑制作用（8-57.2%）。qRT-PCR 结果证实了这一点，表明测试的毒力基因显著下调。下调幅度从 SarA 的 43%至 64.05%，AgrA 的 36.85%至 64.75%，hla 的 50%至 63.2%，FnbA 的 38.55%至 60.35%，IcaA 的 46.75%至 61.05%，SigB 的 27.55%至 64%，CrtM 的 51.05%至 72.8%。总之，双氯芬酸可以与抗生素联合使用，作为抗多药耐药性-MRSA 的抗毒力剂，这将增强免疫系统清除感染的能力。
