Paul B. Savage, Yanshu Feng, and Jake Pollard. Brigham Young University, Provo, UT
Ceragenins are cholic acid-based antimicrobial agents that mimic the amphiphilic morphology of antimicrobial peptides. Antimicrobial peptides selectively disrupt bacterial membranes and are one of Nature's primary solutions for controlling the growth of bacteria in organisms ranging from mammals to insects. The ubiquity of antimicrobial peptides argues that targeting bacterial membranes may be an effective, long-term approach for controlling bacterial growth. As mimics of antimicrobial peptides, ceragenins display potent bactericidal activity against a broad range of bacteria including Gram-negative and positive organisms. Drug-resistant bacteria, including methicillin-, and vancomycin-resistant Staphylococcus aureus, are highly susceptible to ceragenins. As part of their mechanism of action, ceragenins bind to bacterial membrane components and cause membrane depolarization and permeabilization. Due to their relatively small size and affinity for bacterial membranes, ceragenins are active against established bacterial biofilms. As polycations, ceragenins can be sequestered by anionic polymers, and controlled release of ceragenins from thin films on medical devices can be achieved using water-insoluble anionic polymers. Thin films containing ceragenins prevent bacterial biofilm formation on surfaces even in the presence of large inocula of bacteria. Ceragenins are well tolerated by cells types that are normally exposed endogenous antimicrobial peptides. Furthermore, they are relatively easy to synthesize and are much more stable than antimicrobial peptides, that is, they are not substrates for proteases. Consequently, the ceragenins appear well suited for replacing or augmenting the antibacterial activities of antimicrobial peptides.