Anti-MRSA Activity and Molecular Dynamics Simulations of a Novel Peptide from Hevea brasiliensis Latex Protein Waste Hydrolysates

The escalating methicillin-resistant Staphylococcus aureus (MRSA) crisis necessitates urgent therapeutic innovations. C-serum from Hevea brasiliensis is a protein-rich waste byproduct generated during rubber latex production. The primary objective of this research was to discover and evaluate a new antimicrobial peptide generated through the enzymatic digestion of C-serum protein waste. Enzymatic digestion liberated a novel cryptic hexapeptide, LLKKKY (CSPH-AMP). This peptide exhibited potent efficacy against planktonic and biofilm-associated S. aureus TISTR 517 and MRSA strains (142, 1096, and 2468). It demonstrated minimum inhibitory (MIC) and bactericidal (MBC) concentrations of 4 and 16 μg/mL, alongside minimum biofilm inhibitory (MBIC) and eradication (MBEC) concentrations of 16 and 128 μg/mL, respectively. SYTOX Green assays confirmed that the peptide induces rapid membrane permeabilization. Coarse-grained molecular dynamics simulations demonstrated that initial electrostatic peptide adsorption transitions into a bent transmembrane conformation, inducing localized lipid deformation and aqueous channel formation. Complementary proteomic analysis revealed that CSPH-AMP triggers targeted metabolic and structural cellular repair networks to counter membrane depolarization. Furthermore, CSPH-AMP demonstrated excellent thermal and proteolytic stability. By combining rapid membrane-lytic bactericidal action with robust physical stability, CSPH-AMP emerges as a promising, sustainably sourced candidate for future therapeutic development against drug-resistant MRSA.