Antibiotic-resistant bacteria have been a significant concern to medical practice, diminishing the number of available treatment options by antibiotics. There is a compelling need to establish new antimicrobials that are active against antibiotic-resistant bacteria without contributing to emergent resistance development. Our laboratory focuses on a new molecular design of antimicrobial synthetic polymers with alternative mode of antibacterial action for multiple applications including pharmaceutical agents, antimicrobial coatings on catheters and implants, and dental composite fillings.
Antimicrobial peptide-mimetic polymers
To create new antimicrobial materials effective to drug resistant bacteria, our laboratory has developed the molecular mimicry of naturally occurring antimicrobial peptides using synthetic methacrylate polymers. These polymers are designed to mimic the cationic functionality and amphiphilic nature of antimicrobial peptides to act as membrane-active antimicrobial agents. These antimicrobial polymers represent the hallmarks of antimicrobial peptide such as antimicrobial activity against a broad spectrum of bacteria including antibiotic-resistant strains, low propensity for resistance development in bacteria, and no adverse toxicity against host cells.
Bacteria proficiently adhere to synthetic surfaces of medical devices or implants, and establish matrix-encased bacterial communities, known as biofilms. This biofilm formation is a concern because the biofilm matrix protects resident bacteria from host-defense mechanisms and antibiotic challenges, resulting in chronic and recurrent bacterial infections. To prevent the biofilm formation, our laboratory has developed versatile polymeric materials for bactericidal or anti-fouling coatings by utilizing a mussel protein mimetic adhesive group or a star-shaped polymer nano-architecture.
Thoma, L. M.; Boles, B. R. and Kuroda, K. "Cationic Methacrylate Polymers as Topical Antimicrobial Agents against Staphylococcus aureus Nasal Colonization." Biomacromolecules, 2014, 15(8), 2933.
Takahashi, H.; Palermo, E. F.; Yasuhara, K.; Caputo, G. A. and Kuroda, K. "Molecular Design, Structures, and Activity of Antimicrobial Peptide-Mimetic Polymers." Macromol. Biosci., 2013, 13(10), 1285.
Palermo, E. F.; Vemparala, S. and Kuroda, K. "Cationic Spacer Arm Design Strategy for Control of Antimicrobial Activity and Conformation of Amphiphilic Methacrylate Random Copolymers." Biomacromolecules,2012, 13(5), 1632.
Oda, Y.; Kanaoka, S.; Sato, T.; Aoshima, S. and Kuroda, K. "Block versus Random Amphiphilic Copolymers as Antibacterial Agents." Biomacromolecules, 2011, 12(10), 3581.
Kuroda, K. and DeGrado, W. F. "Amphiphilic polymethacrylate derivatives as antimicrobial agents," J Amer. Chem. Soc., 2005, 127, 4128.