Anti-virulence peptides: a compromising strategy to treat Staphylococcus aureus chronic wound infection

Chronic wound infections, particularly those associated with Staphylococcus aureus (S. aureus), present a significant clinical challenge due to biofilm formation and increasing antibiotic resistance. This review explores the emerging role of commensal bacteria and natural compounds in modulating S. aureus virulence, with a focus on the inhibition of the accessory gene regulator quorum-sensing system Agr. We highlight antimicrobial peptides secreted by skin commensals such as Staphylococcus epidermidis (S. epidermidis), Staphylococcus hominis (S. hominis), and Corynebacterium spp., which interfere with agr signaling, biofilm development, and toxin production. Additionally, we examine natural molecules derived from fungi and plants that target Agr and other regulatory systems (e.g. Staphylococcal accessory element Regulator Sensor/Regulator System, Autolysis-related Regulator Sensor/Regulator System and Staphylococcal accessory regulator A), offering promising antivirulence strategies. These findings underscore the therapeutic potential of microbiota-derived and natural antivirulence agents as adjuncts or alternatives to antibiotics. Further research is needed to evaluate their stability, safety, and clinical applicability.