Abstract
Bombolitins, a class of peptides produced by bees of the genus Bombus, target and disrupt cellular membranes, leading to lysis. Antimicrobial peptides exhibit various mechanisms of action resulting from the interplay between peptide structure, lipid composition, and cellular target membrane selectivity. Herein, two bombolitins displaying significant amino-acid-sequence similarity, BII and BL6, were assessed for antimicrobial activity as well as correlated dodecylphosphocholine (DPC) micelle binding and membrane-induced peptide conformational changes. Infrared and circular dichroism spectroscopies were used to assess the structure-function relationship of each bombolitin, and the results indicate that BII forms a rigid and helically ordered secondary structure upon binding to DPC micelles, whereas BL6 largely lacks secondary structural order. Moreover, the binding affinity of each peptide to DPC micelles was determined, revealing that BL6 displayed a difference in binding affinity by over two orders of magnitude. Further investigations into the growth-inhibitory activity of the two bombolitins were performed against Escherichia coli and Saccharomyces cerevisiae. Interestingly, BII specifically targeted S. cerevisiae, whereas BL6 more effectively inhibited E. coli growth. Overall, the antimicrobial selectivity and specificity of BII and BL6 are largely dependent on the primary as well as secondary structural content of the peptides and the membrane composition.