Antibacterial and antibiofilm effects of flufenamic acid against methicillin-resistant Staphylococcus aureus. (October 2020)

• Record Type: Journal Article
• Authors: Zhang, Shutao; Tang, Haozheng; Wang, You; Nie, Bin'en; Yang, Hongtao; Yuan, Weien; Qu, Xinhua; Yue, Bing
• Is Part Of: Pharmacological research. Volume 160(2020)
• Publication Date: 2020-10
• Subjects: CFU colony-forming unit -- CLSM confocal laser scanning microscopy -- DAPI 4′, 6-diamidino-2-phenylindole -- DEG differentially expressed gene -- FICI fractional inhibitory concentration index -- FITC fluorescein isothiocyanate -- H&E hematoxylin and eosin -- KEGG Kyoto Encyclopedia of Genes and Genomes -- MIC minimal inhibitory concentration -- MRSA methicillin-resistant Staphylococcus aureus -- MRSE methicillin-resistant S. epidermidis -- MSSA methicillin-sensitive S. aureus -- NSAID non-steroid anti-inflammatory drug -- RBMSC rat bone marrow mesenchymal stem cells -- RNA-Seq RNA sequencing -- SEM scanning electron microscopy -- SSI surgical site infection -- TSB tryptic soy broth -- TEM transmission electron microscopy; Flufenamic acid (PubChem CID: 3371) -- Vancomycin (PubChem CID: 14969) -- Daptomycin (PubChem CID: 16134395) -- Oxacillin (PubChem CID: 6196); Biofilm -- Flufenamic acid -- Non-steroid anti-inflammatory drug -- Methicillin-resistant Staphylococcus aureus; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.105067
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Highlights: The NSAID flufenamic acid inhibited MRSA growth in vitro. Flufenamic acid enhanced sensitivity of MRSA to the beta-lactam oxacillin. Flufenamic acid prevented biofilm formation on Ti6Al4V discs. Flufenamic acid ameliorated local infection caused by MRSA injection in mice. Abstract: Methicillin-resistant Staphylococcus 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.