Ceragenins and Antimicrobial Peptides Kill Bacteria through Distinct Mechanisms
Gabriel Mitchell, Melanie R. Silvis, Kelsey C. Talkington, Jonathan M. Budzik, Claire E. Dodd, Justin M. Paluba, Erika A. Oki, Kristine L. Trotta, Daniel J. Licht, David Jimenez‐Morales, Seemay Chou, Paul B. Savage, Carol A. Gross, Michael A. Marletta, Jeffery S. Cox
Abstract
The development of novel antibiotics is essential because the current arsenal of antimicrobials will soon be ineffective due to the widespread occurrence of antibiotic resistance. The development of naturally occurring cationic antimicrobial peptides (CAMPs) for therapeutics to combat antibiotic resistance has been hampered by high production costs and protease sensitivity, among other factors. The ceragenins are a family of synthetic CAMP mimics that kill a broad spectrum of bacterial species but are less expensive to produce, resistant to proteolytic degradation, and seemingly resistant to the development of high-level resistance. Determining how ceragenins function may identify new essential biological pathways of bacteria that are less prone to the development of resistance and will further our understanding of the design principles for maximizing the effects of synthetic CAMPs.