Disruption of MRSA Biofilm and Virulence by Deep-Sea Probiotics: Impacts on Energy metabolism and Host Antimicrobial Peptides

Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant threat to public health due to its resistance to conventional antibiotics and its ability to form robust biofilms on both biotic and abiotic surfaces. In this study, we explore the novel mechanisms by which deep-sea-derived probiotics serve as an alternative strategy to combat MRSA infections. Three promising probiotic candidates, Lactococcus lactis (L25_4) and two strains of Leuconostoc pseudomesenteroides (L25_6 and L25_7), were isolated from ocean water collected at a depth of 312 m off the eastern coast of Taiwan. Each candidate strain demonstrated potent antimicrobial activity, significantly reducing MRSA biofilm formation when applied to pork skin. The strains also improved survival rates in a Galleria mellonella infection model (> 90% survival). Immunomodulatory effects were evident, with marked upregulation of Cecropin antimicrobial peptide (AMP) and downregulation of Gloverin AMP in the host. Scanning and transmission electron microscopy (SEM and TEM) revealed that probiotic treatments compromised MRSA cell membrane integrity, consistent with transcriptomic analysis showing downregulation of genes related to protein translation, membrane structure, and transporter systems. Collectively, our comprehensive in vitro, in vivo, ex vivo, and transcriptomic analyses reveal the intricate mechanisms by which deep-sea probiotics modulate both host and MRSA gene expression, underscoring their potential as innovative tools for addressing antibiotic-resistant infections.