Effect of charge on the antimicrobial activity of alpha-helical amphibian antimicrobial peptide

Antibiotic resistance is a severe threat to the world's public health, which has increased the need to discover novel antibacterial molecules. In this context, an emerging class of naturally occurring short peptide molecules called antimicrobial peptides (AMPs) has been considered potent antibacterial agents. Amphibians are one of the significant sources of AMPs, which have been extensively studied for the last few decades. Most amphibian AMPs are cationic, and several of these cationic AMPs adopt a well-defined alpha-helical structure in the presence of bacterial membranes. These cationic alpha-helical amphibian AMPs (CαAMPs) can selectively and preferentially bind with the negatively charged surfaces of Gram-positive and Gram-negative bacteria through electrostatic interaction, considered the main reason for their antibacterial activities. Here, we categorized these CαAMPs according to their charge, and to calculate the charge density; we divided the charge of each peptide by its corresponding length. To investigate the effect of charge among these categories, charge or charge density under each charge category was plotted against their corresponding minimum inhibitory concentration (MIC). Moreover, the effect of charge modification of some CαAMPs under specific charge categories in the context of MIC and hemolysis was also discussed. The information in this review will help us understand the antibacterial activity of accessible CαAMPs depending on each charge category across species. Additionally, this study suggests that designing novel functional antibacterial agents requires charge modification optimally.