Efficiency of NSAIDs in preventing prosthetic joint infections (PJIs): inhibition of Staphylococcus aureus biofilms by etoricoxib through down regulation of bacterial adhesion genes.

内容摘要

Biofilm-associated prosthetic joint infections (PJIs) are becoming an increasing public health concern due to their ability to form biofilm on prosthetic implants and cause significant morbidity owing to antibiotics resistance. Therefore, new drugs and management procedures are required to improve the treatment outcome for PJIs and the drug repurposing is an excellent method to develop new antimicrobials. Thus, the present study evaluated etoricoxib, a selective COX2 inhibitor for its antibacterial and antibiofilm activities against Staphylococcus aureus - one of the major biofilm-forming bacteria causing the PJIs. The anti-S. aureus potential of etoricoxib was analyzed and the minimum inhibitory concentration (MIC) was found to be as low as 25 µg/mL. The killing-kinetics of etoricoxib was observed at 2 h and the drug showed synergistic effect along with ampicillin and tetracycline, reducing the MIC by 4-fold. Further, etoricoxib exhibited antibiofilm activity by inhibiting biofilm formation and displaying mature biofilm eradication by 90% after the treatment. To prevent biofilm formation on implant material, etoricoxib was coated on the implant material and it reduced 80% of bacterial attachment which was further confirmed by FDA/PI staining that revealed 79% of dead cells on the coated material. The docking analysis revealed the strong binding affinity of etoricoxib towards bacterial biofilm adhesion proteins and the drug downregulated the biofilm adhesion protein encoded genes namely icaA, clfA, cna, fnbA, and fib expression levels after the treatment. Moreover, etoricoxib treatment caused S. aureus cell damage resulting in cell death and was noticed through scanning electron microscope (SEM) analysis. Thus, as etoricoxib was effective in eliminating and preventing biofilms and the authors recommend further in vitro and in vivo studies to explore the possibility for new therapeutic option for implant-associated infections.