Abstract :Antimicrobial Peptides (AMPs) are one of the most promising future strategies for defeating the
antibiotic resistance. Alpha Melanocyte Stimulating Hormone (a-MSH) is a cationic neuropeptide
and we have previously reported its strong in vitro antimicrobial activity against Staphylococcus
aureus. However, the efficacy of this peptide needs to be tested against a large number of clinical
S. aureus isolates to ascertain its antistaphylococcal potential. Moreover, in vivo efficacy of alphaMSH
need to be determined for establishing its biological significance. In the present study, we
tested the susceptibility of a total of 100 clinical S. aureus isolates, including 43 MSSA and 57 MRSA
towards a-MSH and found that 10 µg/ml of a-MSH killed 95% and 77% of MSSA and MRSA
strains, respectively. To check if cross resistance existed among the a-MSH-non-susceptible strains,
a susceptibility profiling test was done towards three other AMPs belonging to different sources.
We chose gramicidin D, magainin 2 and human neutrophil peptide 1 for this purpose and it was
observed that cross resistance was not present among the study strains. We further evaluated in
vivo efficacy of a-MSH against S. aureus using mice intravenous and skin wound infection models.
Results revealed that the therapeutic efficacy of a-MSH at 8 mg/kg is superior to that of oxacillin in
animal infection model, leading to 100% survival of the S. aureus infected animals. The effectiveness
of a-MSH both in vitro and in vivo models further strengthened the clinical potential of this peptide.