NSF Award
2327691
The broader impact of this I-Corps project is to provide technology to combat the development of antimicrobial resistance in fungi. There are only three main classes of antifungal drugs used to treat the most common fungal infections. Species such as Cryptococcus neoformans have resistance to a large portion of one or more classes of antifungals. This means that much higher doses of these drugs are needed than usual. Clinical management of these cases can be difficult, causing extreme health difficulties as well as economic hardships for vulnerable populations like people who are elderly or who are immunocompromised with HIV/AIDS. The issues are further exacerbated by poor antimicrobial stewardship in agriculture where overuse of these same antifungals is leading to a rise in drug resistance even outside of the clinic. Technology is needed to improve the activity of existing antimicrobial drugs and make them safe and effective for use against even the most challenging drug-resistant strains. This project seeks to identify the market potential for technology that can lower the doses of drugs needed to treat resistant fungi. This technology has the potential to impact a multi-billion-dollar industry and keep the existing classes of antifungals useful for many years to come. <br/><br/>The project is based on the development of antimicrobial peptides from the outer loop region of the C. neoformans P4-ATPase enzyme. The enzyme controls the movement of lipids from the outer surface of the cell to the inside of the cell. The fungus C. neoformans is resistant to the drug Caspofungin. It was found that removing cdc50 makes treatment with caspofungin easier. Preventing the movement of lipids leaves the fungal cells vulnerable to attack from caspofungin and some of the main classes of antifungal drugs. The antimicrobial peptides block the movement of the lipids, and they can therefore be used in a combination treatment with other antifungal drugs. To this end, a patent has been filed to support the development of the technology. Several papers have been published and/or are in preparation related to this technology. Work will continue to be done to improve the peptide activity and make the most effective treatment possible.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
