Facial Amphiphilic Antimicrobials Biomaterials Containing Fused Multicyclic Structures

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Non-technical: This award by the Biomaterials program to University of South Carolina at Columbia is to advance the knowledge of a class of antimicrobial agents. This award is co-funded by the following programs: 1) BMAT program in the Division of Materials Research; and 2) Biotechnology and Biochemical Engineering program in the Division of Chemical and Bioengineering, Environmental, and Transport Systems (ENG). Bacterial infections have now evolved into a global healthcare crisis. The ever-increasing emergence of bacterial resistance to traditional antibiotics is a puzzling issue in battling infectious diseases. One direct outcome of this program would be the development of prototype antimicrobial compounds and polymers. This project will provide training opportunities to graduate and undergraduate students in the polymer synthesis, modeling and antimicrobial compounds. Several integrated educational activities for high school, undergraduate and graduate students will be carried out to stimulate their interest in science and technology. This project will continue to expand the highly successful Project Seed Summer Research Program to high school students from economically disadvantaged families. Other activities involving K-12 students include a series of presentations called "Small World with Big Impacts: Nanobiology" and biomolecular visualization workshops. This project will also train students from underrepresented groups. These programs would also serve as integrated educational experience for academically bound graduate students. Research results and discoveries will be disseminated with publications in peer-reviewed journals and presentations at national and international conferences.Technical: This project is an integrated research, education, and outreach program in designing a class of multicyclic terpenoid-derived facial amphiphilic compounds and polymers as robust antimicrobial agents, which could kill a variety of bacteria, particularly multidrug resistant bacterial strains, while maintaining minimal cytotoxicity against mammalian cells. The major approach relies on a combination of hydrophobic fused multicyclic di- and tri-terpenoids and ionic motifs. This project includes fundamental biomaterials research on designing facial amphiphilic structures, uncovering mechanisms of action against bacteria, and fighting vexing bacterial resistance. The main aims of this project are to: 1) synthesize and characterize facial amphiphilic compounds and polymers from carnosic acid, cholic acid and glycyrrhetinic acid, and evaluate their antimicrobial activities; 2) design macromolecular nanostructures as a new tool to fighting bacterial resistance; and 3) model mechanisms of action between facial amphiphilic antimicrobial agents and bacterial cell membranes. The ultimate goal is to translate the most desirable and unique properties of terpenoid-based cationic compounds and polymers into new classes of antimicrobial agents with functionality and performance that are unprecedented for current antimicrobial materials.