AUTHOR=Bui Ly Tuan Kiet , Bushra Fariha Alam , Rattananon Pirachat , Rimi Arifa Afrose , Lee Carmen , Tahmid S. M. , Tisha Sumaiya Akter , Jisan Irfan Fayaz , Das Rachita , Sneha Jahin Ibnat , Pitts Victoria , Owasanoye Olalekan Uchechukwu , Khadka Saphal , Islam Shariful TITLE=Strategic antagonism: how Lactobacillus plantarum counters Staphylococcus aureus pathogenicity JOURNAL=Frontiers in Microbiology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2025.1635123 DOI=10.3389/fmicb.2025.1635123 ISSN=1664-302X ABSTRACT=Staphylococcus aureus is a clinically significant pathogen known for its antibiotic resistance, immune evasion, and biofilm formation, making it a major contributor to persistent infections. Lactobacillus plantarum, a versatile probiotic bacterium, has emerged as a promising antagonist against S. aureus through multifaceted inhibitory mechanisms. This review synthesizes current evidence on the antagonistic interactions between L. plantarum and S. aureus, highlighting bacteriocin-mediated membrane disruption, quorum sensing interference, biofilm degradation, and metabolic competition. In addition, we explore how L. plantarum contributes to a less favorable inflammatory environment for S. aureus by modulating local immune responses at infection sites. Clinical relevance is explored across diverse anatomical sites such as the skin, vaginal tract, urinary system, and gastrointestinal tract, where L. plantarum demonstrates both direct and adjunctive therapeutic potential. We also consider environmental influences like pH and nutrient availability that modulate this antagonism. Together, the findings position L. plantarum as a compelling candidate for probiotic-based interventions against persistent and device-associated S. aureus infections.