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Investigation of Lytic Activity of Melittin‐nNOS Chimeric Antimicrobial Peptides
Author(s) -
Fujii Maria,
StevensTruss Regina
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.809.3
Subject(s) - melittin , antimicrobial peptides , lytic cycle , peptide , antimicrobial , chimera (genetics) , liposome , lysis , amino acid , biochemistry , chemistry , peptide sequence , staphylococcus aureus , cytotoxicity , cytotoxic t cell , biology , microbiology and biotechnology , bacteria , gene , in vitro , virology , virus , genetics
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 the nNOS enzyme 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 activities of a series of Mel‐nNOS chimeras. In this study, the chimeras were produced by replacing the middle 10 residues of one peptide with that of the other ( nMel‐nNOS‐cMel and nnNOS‐Mel‐cnNOS ). 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 red blood cells (RBCs). The results show that both truncated peptides were completely inactive. In addition, both chimeras were found to effectively cause liposome lysis at concentrations below 3 uM and have minimal effect on RBC lysis. Chimera nnNOS‐MelcnNOS was found to have IC 50 values above 12 uM for both S. aureus and E. coli while chimera nMel‐nNOS‐cMel was found to be more selective for S. aureus (IC 50 values between 4 uM and 8 uM), with IC 50 for E. coli being greater than 16 uM. 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. Support or Funding Information The Authors would like to acknowledge the American Society for Biochemistry and Molecular Biology, as well as the Kalamazoo College Chemistry Department and Faculty Development Committee for funding. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .