An Investigation into the Lytic Activity of Melittin-nNOS Chimeric Peptides
Fujii, Maria E.
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Antibiotic resistance has become a growing problem in a world of prescription drug overuse and misuse. Antimicrobial peptides (AMPs) offer one possible solution. Melittin (Mel), isolated from bee venom, is a known AMP. It is active against a variety of microbes as well as cytotoxic towards eukaryotic cells. Previous work from our lab has demonstrated that the calmodulin-binding sequence of neuronal nitric oxide synthase (nNOS) possesses selective activity against S. aureus. Our lab has been investigating the role that specific amino acid residues of Mel play in its lytic activities, and possibly what role these amino acids play in selectivity, by investigating the lytic activities of a series of Mel-nNOS chimeras. In this study, two chimeras were produced by replacing the middle 10 residues of one peptide with that of the other (nMel-nNOS-cMel and nnNOS-MelcnNOS). We also assessed the activity of Mel truncated peptides (nMel and cMel). All experimental peptides were tested for their ability to inhibit the growth of S. aureus and E. coli as well as their ability to lyse liposomes and human red blood cells (RBCs). The results show that both truncated peptides were completely inactive. Both chimeras were found to effectively cause liposome lysis at concentrations below 5 μM and have minimal effect on RBC lysis. Chimera nnNOS-Mel-cnNOS was found to have IC50 values above 12 μM for both S. aureus and E. coli while chimera nMel-nNOS-cMel was found to be more selective for S. aureus (IC50 values between 4 μM and 8 μM), with IC50 for E. coli being greater than 16 μM. These results imply that the eight terminal residues of Mel are insufficient for bacterial growth inhibition. Further studies should focus on increasing the Mel to nNOS ratio of the chimeric AMPs.