Antibacterial and antibiofilm effects of flufenamic acid against methicillin-resistant Staphylococcus aureus
Antibacterial and antibiofilm effects of flufenamic acid against methicillin-resistant Staphylococcus aureus
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氟芬那酸对耐甲氧西林金黄色葡萄球菌的抗菌和抗生物膜作用
DOI：
10.1016/j.phrs.2020.105067
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发表时间：
2020
影响因子：
9.3
通讯作者：
Bing Yue
中科院分区：
文献类型：
--
作者：
Shutao Zhang;Haozheng Tang;You Wang;Bin’en Nie;Hongtao Yang;Weien Yuan;Xinhua Qu;Bing Yue
耐甲氧西林金黄色葡萄球菌（MRSA）感染是外科手术最严重的并发症之一，其预防至关重要。氟芬那酸是一种非甾体抗炎药，被批准用于临床，以缓解类风湿关节炎患者的炎症和疼痛。在这项研究中，我们探讨了氟芬那酸的抗菌效果和这种效果的机制。通过最小抑菌浓度（MIC），时间-杀灭，耐药诱导试验，和抗生素协同试验，我们证明，氟芬那酸抑制甲氧西林耐药葡萄球菌的生长，并没有诱导耐药性时，它在MIC使用。此外，氟芬那酸与β-内酰胺抗生素苯唑西林协同作用，对哺乳动物细胞没有显着毒性。生物被膜抑制实验表明氟芬那酸能阻止医用植入物上细菌生物被膜的形成，并能破坏细菌细胞壁的超微结构。RNA测序和定量RT-PCR表明，氟芬那酸抑制与肽聚糖的生物合成，β-内酰胺类抗生素，群体感应，生物膜形成相关的基因的表达。此外，氟芬那酸有效地改善了由MRSA引起的小鼠局部感染。总之，氟芬那酸可能是一种有效的治疗化合物对MRSA感染和一个有前途的候选人的抗菌涂层的植入物和手术装置。
Methicillin-resistantStaphylococcus aureus(MRSA) infections are one of the most serious surgery complications, and their prevention is of utmost importance. Flufenamic acid is a non-steroid anti-inflammatory drug approved for clinical use to relieve inflammation and pain in rheumatoid arthritis patients. In this study, we explored the antibacterial efficacy of flufenamic acid and the mechanisms underlying this effect. By using minimal inhibitory concentration (MIC), time-kill, resistance induction assays, and the antibiotic synergy test, we demonstrated that flufenamic acid inhibited the growth of methicillin-resistant staphylococci and did not induce resistance when it was used at the MIC. Furthermore, flufenamic acid acted synergistically with the beta-lactam antibiotic oxacillin and did not show significant toxicity toward mammalian cells. The biofilm inhibition assay revealed that flufenamic acid could prevent biofilm formation on medical implants and destroy the ultrastructure of the bacterial cell wall. RNA sequencing and quantitative RT-PCR indicated that flufenamic acid inhibited the expression of genes associated with peptidoglycan biosynthesis, beta-lactam resistance, quorum sensing, and biofilm formation. Furthermore, flufenamic acid efficiently ameliorated a local infection caused by MRSA in mice. In conclusion, flufenamic acid may be a potent therapeutic compound against MRSA infections and a promising candidate for antimicrobial coating of implants and surgical devices.