Synthetic Antimicrobial Peptide Tuning Permits Membrane Disruption and Interpeptide Synergy
Francisco R. Fields, Giorgia Manzo, Charlotte K. Hind, Jeshina Janardhanan, Ilona P. Foik, Phoebe Do Carmo Silva, Rashna D. Balsara, Melanie Clifford, Henry M. Vu, Jessica Ross, Veronica R. Kalwajtys, Alejandro Gonzalez, Tam T. T. Bui, Victoria A. Ploplis, Francis Castellino, Albert Siryaporn, Mayland Chang, J. Mark Sutton, A. James Mason, Shaun W. Lee
Abstract
The ribosomally produced antimicrobial peptides of bacteria (bacteriocins) represent an unexplored source of membrane-active antibiotics. We designed a library of linear peptides from a circular bacteriocin and show that pore-formation dynamics in bacterial membranes are tunable via selective amino acid substitution. We observed antibacterial interpeptide synergy indicating that fundamentally altering interactions with the membrane enables synergy. Our findings suggest an approach for engineering pore-formation through rational peptide design and increasing the utility of novel antimicrobial peptides by exploiting synergy.