Anti-biofilm effect and inhibition of cell wall synthesis in foodborne Staphylococcus aureus by rafoxanide, an anthelmintic drug

Résumé fourni par la source

Staphylococcus aureus is a major foodborne pathogen whose increasing antimicrobial resistance and biofilm-associated persistence threaten dairy safety. The declining efficacy of conventional antibiotics underscores the need for alternative strategies. This study evaluated the antibacterial activity of rafoxanide against dairy-associated S. aureus and its effects on biofilm and cell wall biosynthesis. From 483 raw milk samples, 100 S. aureus isolates were identified, including 27 amoxicillin-resistant strains and 5 MRSA strains. Molecular typing identified ST398 and MRSA ST59-t437-SCC mec IV as predominant lineages. All isolates were highly susceptible to rafoxanide, with an MIC of 1 μg/mL. Rafoxanide primarily interfered with the initial adhesion stage of biofilm development, inhibiting biofilm formation and partially disrupting mature biofilms. This effect was associated with reduced extracellular polymeric substance production and downregulation of adhesion-related genes ( srtA and clfB ). Transcriptomic profiling and ultrastructural analysis indicated disruption of peptidoglycan and teichoic acid pathways. Molecular docking suggested interactions with multiple wall teichoic acid biosynthetic enzymes, supporting a multi-target mode of action. Additionally, rafoxanide enhanced β -lactam susceptibility in resistant isolates, and no MIC increase was observed during 15 days of serial passage. These findings highlight the potential of rafoxanide as an alternative strategy for controlling S. aureus contamination in dairy systems.

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