Potential of Jelleine-I peptide on down-regulation of biofilm-associated genes and the biofilm formation of methicillin-resistant Staphylococcus aureus.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen with strong biofilm-forming ability, contributing to persistent infections and antibiotic resistance. This study evaluated the antibiofilm activity of Jelleine-I against MRSA and its effects on the expression of biofilm-associated genes. METHODS: Antibacterial activity was assessed by the broth microdilution method and time–kill assays, while biofilm inhibition and disruption were evaluated using the microplate assay and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Resistance development was monitored over 28 days, with vancomycin as a control, and hemolytic activity was tested on human red blood cells (RBCs). RESULTS: Jelleine-I showed a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 128 µM, eliminating MRSA within four hours at MIC. It inhibited biofilm formation by over 77%, disrupted mature biofilms by more than 40%, and reduced metabolic activity by over 80%. The MIC remained unchanged after 28 days, whereas vancomycin MIC increased fourfold. Jelleine-I exhibited low hemolytic activity and significantly downregulated fib (2.47-fold), icaA (2.22-fold), and icaD (1.25-fold) expression after 12 h. CONCLUSIONS: These findings demonstrate that Jelleine-I effectively targets MRSA biofilms at both phenotypic and genetic levels, supporting its potential as a candidate for further cytotoxicity and in vivo studies.