Targeting phenol-soluble modulins: eco-friendly theragnostic strategies against Staphylococcus aureus biofilms

The growing resistance to antibiotics by Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) is a global health threat. Traditional antibiotics act on the viability of bacteria, whereas new ones are now increasingly targeting virulence factors. Phenol-soluble modulins (PSMs) are essential virulence factors that play important roles in inflammation, neutrophil lysis, cytotoxicity and biofilm formation. PubMed, Scopus, Web of Science and Google Scholar were used for literature search of articles published between 2010 and 2026. Green-synthesized metal nanoparticles (NPs) have been found to be capable of altering these mechanisms by inducing reactive oxygen species (ROS) production, membrane damage, and by interfering with the quorum-sensing mechanism of the bacteria, along with inhibiting the Agr system. Optimization of NP-based interventions can be supported by multi-omics approaches such as genomics, transcriptomics, proteomics and metabolomics. Other potential methods of targeted PSM pathway and Agr pathway suppression are also available, such as CRISPR-Cas9 and dCas9, but there are delivery difficulties. The potential use of combining nanotechnology, gene editing, multi-omics, artificial intelligence, and synthetic biology could allow for development of more advanced anti-virulence strategies against S. aureus infections targeted at PSM.