Antimicrobial efficacy of viridicatol derived from P. crustosum S14 against MRSA: Mechanistic insights from a comprehensive multi-omics analysis

Methicillin-resistant Staphylococcus aureus (MRSA) presents a formidable challenge to public health, necessitating alternative strategies to address the superbug-related infections. This study systematically evaluates the antibacterial efficacy of Viridicatol, a compound isolated from the fermentation products of Penicillium crustosum derived from marine. Special emphasis was placed on its potent activity against MRSA USA300. Through a comprehensive suite of morphological, biophenotypic, genomic, and metabolomic analyses, we elucidate the mechanisms of action of this agent. Our findings reveal that Viridicatol exhibits significant bactericidal effects, primarily through the disruption of bacterial structural integrity and the induction of severe intracellular metabolic disturbances. These effects were further corroborated in an animal full-thickness wound infection model. Our study provides both a foundational understanding and mechanistic insight into Viridicatol, while also shedding light on the clinical control and management of MRSA.