Abstract
In earlier reports, we have shown the antimicrobial activity of a host neuropeptide, alpha-melanocyte stimulating hormone (α-MSH) and its cationic analogues against Staphylococcus aureus. These analogues of α-MSH showed enhanced staphylocidal activity without any significant mammalian cell toxicity. Therefore, here, we explored the antimicrobial activity of α-MSH and its cationic analogues against Escherichia coli. Though the presence of lipopolysaccharide (LPS) in Gram-negative bacteria enables them to resist most conventional antibiotics, encouragingly α-MSH and its four analogues showed killing of both logarithmic and stationary phase E. coli cells in a time, dose and cationicity-dependent manner. In fact, the most cationic analogue, KKK-MSH with a + 5 charge, demonstrated successful eradication of 105 CFU/mL of E. coli cells within 15 min at a concentration as low as 1 µM. BC displacement experiment revealed that cationicity of the peptides was directly related to the killing efficacy of these α-MSH analogues against E. coli cells via initial LPS-binding, leading to rapid disruption of the LPS-outer membrane complex followed by inner bacterial membrane damage and eventual cell death. Here, we propose α-MSH based cationic peptides as promising future agents with broad-spectrum antibacterial efficacy against both Gram-negative and Gram-positive pathogens.