Pakistan Journal of Pharmaceutical Sciences

Abstract: The rising incidence of antibiotic resistance in bacterial pathogens, notably methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (S. epidermidis), poses a considerable challenge to global public health. Conventional antibiotic treatments are increasingly undermined by the swift emergence of resistance. In light of this, anti-virulence strategies have gained attention as a viable alternative, concentrating on inhibiting the production of virulence factors instead of directly eliminating bacteria. The current study investigated the anti-virulence properties of the free QQ-5 peptide in relation to both S. epidermidis and MRSA. In vitro experiments, including a hemolysis assay, revealed a reduction in hemolytic activity for both bacterial strains upon the introduction of the QQ-5 peptide. Additionally, the MTT assay conducted with endothelial cells validated the safety profile of QQ-5, as no significant cytotoxic effects were detected. Moreover, kinase activity assays indicated that QQ-5 effectively and inhibits the phosphorylation of AgrC, highlighting its mechanism of action. The results of these studies suggest that QQ-5 specifically inhibits AgrC kinase in the agr system, representing a mechanistically distinct approach compared to conventional quorum-quenching strategies. QQ-5 exhibits robust anti-virulence activity and holds significant promise as a therapeutic agent for the treatment of MRSA and S. epidermidis infections.