Executive Summary : | ?-Melanocyte Stimulating Hormone (?-MSH) is an endogenous neuro, tridecapeptide, known for its anti-inflammatory and antipyretic activity. To elucidate the role of its amino acid sequences in staphylocidal mechanism, investigated the antimicrobial activity of different fragments of ?-MSH and compared with whole peptide. C-terminal containing peptides ?-MSH(6-13), ?-MSH(11-13) efficiently killed Staphylococcus aureus cells even in presence of salt and their efficiency were as comparable as entire ?-MSH, whereas N-terminal region ?-MSH(1-5) was found to be ineffective against S. aureus. Similar to the parent peptide ?-MSH, ?-MSH (6-13), ?-MSH (11-13) depolarized and permeabilized Staphylococcus cells. Furthermore, scanning and transmission electron microscopy showed remarkable morphological changes on S. aureus cell surface due to exposure of ?-MSH and its C-terminal fragments. Like whole peptide, ?-MSH (6-13) was very effective against clinical MRSA strains whereas ?-MSH (11- 13) was effective against clinical MSSA strains. Moreover, ?-MSH and ?-MSH (6-13) showed negligible cytotoxic effects. The in vitro synergistic potential of ?-MSH with five selected conventional antibiotics viz., oxacillin (OX), ciprofloxacin (CF), tetracycline (TC), gentamicin (GM) and rifampicin (RF) against a clinical resistant MRSA strain. The supplementation of ?-MSH with GM, CF and TC resulted in ? 64, 8 and 4 fold reductions in their minimum bactericidal concentrations (MBCs), respectively. Thus, present observations indicated that C-terminal fragments of ?-MSH retain antimicrobial activity of whole peptide, and their mechanism of action is similar to that of entire peptide. The synergistic activity of ?-MSH with antibiotics is encouraging, and promises to restore the lost potency of discarded antibiotics. These observations are important and critical in rational designing of ?-MSH based therapeutics with optimal efficacy. |