Piroxicam repurposing approach as an anti-virulence agent against methicillin resistant Staphylococcus aureus clinical isolates

Abstract

Background: Methicillin resistant Staphylococcus aureus (MRSA) is a major pathogen that causes infections in a wide range due to its high virulence. Anti-virulence therapy is one of several strategies proposed to counteract antimicrobial resistance. FDA-approved drugs repurposing as antibacterial and anti-virulence agents is a promising and rapid approach. The study aimed to evaluate piroxicam effect, a repurposed drug, as anti-virulence agent against MRSA isolated from chronic infections. Methods: The minimum inhibitory concentration (MIC) of piroxicam against the MRSA isolates was estimated. The presence of various virulence factors including protease, hemolysin, staphyloxanthin and biofilm formation was assessed in the absence and presence of piroxicam at ½ MIC. The detection of agr genes was performed using PCR for agr typing of the isolates. Molecular docking studies was performed to investigate whether piroxicam can bind to specific virulence proteins. Results: Piroxicam exhibited an MIC of 2.5mg/ml against all tested isolates. Piroxicam ½ MIC caused a significant reduction in protease activity (20-100% inhibition), hemolysin activity (20.7-97.2% inhibition) and staphyloxanthin production (1.17 -94.63% inhibition). In terms of biofilm formation, there was a significant inhibition ranging from 4.6-76.1%. The isolates were either type agr1 (53.3%) or type agr3 (46.7%). The anti-virulence effect of piroxicam was confirmed through in-silico docking, which demonstrated interactions between piroxicam and virulence proteins. Conclusions: Piroxicam has significant anti-virulence and anti-biofilm effects at sub-MIC against MRSA isolates. Therefore, it can be concluded that piroxicam can be used as an anti-virulence agent against MRSA infections.