Aim: In order to search for novel antibacterial therapeutics against Gram-negative bacteria, the antibacterial efficacies and mechanism of action of tryptophan- and arginine-rich α-melanocyte-stimulating hormone analogs were investigated. Materials & methods: We performed a killing assay to determine their efficacy; fluorescence, microscopic studies were used to understand their mechanism and peptide-lipopolysaccharide interaction. A checkerboard assay was used to find the effective combination of peptide and antibiotics. Results: Ana-peptides displayed good killing activity against Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Their strong interaction with lipopolysaccharide damaged the bacterial membranes and led to their subsequent death. Ana-5, the highest cationic and hydrophobic analog, emerged as the most potent peptide, showing synergistic action with rifampicin and erythromycin. Conclusion: Ana-5 can be presented as an important therapeutic candidate against bacterial infections.
Keywords: Gram-negative bacteria; antimicrobial peptides; synergy; α-melanocyte-stimulating hormone.
Bacteria can cause infections. These infections are becoming harder to treat, because excessive use of antibiotics can cause these bacteria to become less susceptible to medicine. In hospitals, these bacteria can cause infections in the lungs, urinary tract, blood, or on the skin. Our bodies make small molecules called antimicrobial peptides (AMPs) to fight against bacteria. AMPs can weaken or quickly destroy bacteria by attaching to their surfaces and breaking them down. Our laboratory has made an AMP called Ana-5. Using Ana-5 with regular medicine is better at killing bacteria. Ana-5 is not only good at fighting these bacteria, but may also help to prevent future infections.