Suppression of Quorum Sensing and Virulence Factors by Meloxicam and Celecoxib in Methicillin-Resistant Staphylococcus aureus Clinical Isolates

Abstract

Background: Staphylococcus aureus is a major cause of life-threatening infections, and increasing antimicrobial resistance necessitates alternative therapeutic strategies. This study evaluated the antiquorum sensing and antivirulence activities of selected nonsteroidal anti-inflammatory drugs (NSAIDs) against S. aureus clinical isolates by targeting the accessory gene regulator (agr). Methods: Antimicrobial susceptibility and virulence factor production were evaluated in 56 S. aureus clinical isolates. The MICs of six NSAIDs (Diclofenac, ketoprofen, ketorolac, meloxicam, indomethacin and celecoxib) were determined by broth microdilution, and the effects of sub-MICs (½ and ¼ MIC) on virulence factors were assessed. The expression of agrA, hlb, and hld was analyzed by qRT-PCR, and molecular docking was performed to evaluate interactions with AgrA receptor. Results: Among the isolates, high resistance rates were accompanied with cefoxitin, ceftazidime, and cefepime. Hemolysin, protease, and lipase production were detected in 42.86%, 89.28%, and 94.64% of isolates, respectively. Meloxicam and celecoxib at sub-MIC levels significantly reduced hemolysin, protease, and lipase activities. Additionally, both drugs markedly downregulated agrA expression by 88.9–95.3% and significantly reduced hlb and hld expression by 90.5–99.9% without affecting bacterial growth. Molecular docking demonstrated favorable binding interactions with AgrA. Conclusions: Meloxicam and celecoxib could be promising adjunctive therapies against S. aureus through suppression of the Agr-regulated virulence traits.