Anti-quorum sensing mediated anti-infective efficacy of pentadecanoic acid against Staphylococcus aureus infections through in vitro, and in silico analyses

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant human pathogen that is recognized for its tendency to produce biofilms, which plays a role in the development of antibiotic resistance and chronic infections. Since quorum sensing (QS) systems and biofilm formation are essential to S. aureus pathogenicity, they are significant targets for therapeutic intervention. Pentadecanoic acid (PA) was identified in Hydnocarpus wightianus seed extract. It's odd-chain saturated fatty acid with numerous benefits for cardiovascular, immunological, and liver function. It was found to be non-cytotoxic at all concentrations tested, with dose-dependent, broad anti-inflammatory and antiproliferative properties. PA showed concentration-dependent antibacterial action and its sub-inhibitory doses significantly decreased biofilm formation in all S. aureus strains. In addition, PA substantially lowered the formation of extracellular polymeric substance (EPS), protease activity, microbial adhesion, and motility, demonstrating its capacity to reduce bacterial pathogenicity. Microscopic examination revealed that the PA-treated cells had reduced biofilm development. The production of the virulence factor staphyloxanthin by S. aureus strains were substantially reduced in the presence of PA. Strong binding affinities of PA were found by molecular docking experiments to important target proteins associated with biofilm and QS, such as collagen adhesin (cna; PDB ID-1AMX), AgrA (PDB ID-4G4K), AgrC (PDB ID-4BXI), SarA (PDB ID-2FNP), and dehydrosqualene synthase (CrTM; PDB ID-2ZCO). The stability of PA with the S. aureus protein complex was further validated by molecular dynamics simulations. PA has the potential to be an efficient anti-virulence drug against S. aureus infections, providing a possible route for alternative therapies.