Targeting the quorum sensing mechanism in gram-positive strains using therapeutic peptides: A promising quorum quenching approach | [Pakistan Journal of Pharmaceutical Sciences • 2025]

Author(s):

1. Naifa Alenazi: Department of Pharmaceutical Science, College of Pharmacy, Princess Nourah bint Abdulrahman University,P.O. Box 84428, Riyadh 11671,Saudi Arabia

2. Hanan K Alghibiwi: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University,Riyadh 11451,Saudi Arabia

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, antivirulence 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 QQ5 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.

Page(s): 2105-2110

DOI: 10.36721/PJPS.2025.38.6.REG.14118.1

Published: Journal: Pakistan Journal of Pharmaceutical Sciences, Volume: 38, Issue: 6, Year: 2025

Keywords:

Resistance , Staphylococcus epidermidis , MethicillinResistant Staphylococcus aureus , QQ5 peptide , Antivirulence

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