The National Institute of Allergy and Infectious Diseases has awarded $3.7 million to Kirk Hevener, PharmD, PhD, associate professor in the Department of Pharmaceutical Sciences at the University of Tennessee Health Science Center College of Pharmacy, for a project to develop new treatments for Clostridioides difficile (C. diff) infection, a serious and often deadly bacterial infection of the colon.

Drug-resistant strains of C. diff cause severe health problems, including life-threatening inflammation of the colon. Infection can lead to dehydration, kidney failure, and even death. With relapse rates as high as 35%, nearly 30,000 deaths annually, and a national health care cost exceeding $6.3 billion, there is an urgent need for new treatments, especially for recurrent C. diff infection (CDI).

Dr. Hevener's lab has identified a key bacterial enzyme, FabK, as a promising target for new drugs to treat CDI. FabK is essential for the bacteria to make fatty acids, which are a key component of the bacteria's cell membrane. Inhibiting this enzyme has shown strong antibacterial effects in animal studies, effectively treating CDI while showing minimal disruption to the normal gut flora.

With this new award, Dr. Hevener's team aims to improve the potency of their lead FabK inhibitor series, discover and develop new types of FabK inhibitors, and demonstrate the effectiveness of these inhibitors in treating CDI with minimal impact on the gut microbiome.

To achieve these goals, Dr. Hevener has assembled a team with expertise in microbiology, biochemistry, structural biology, synthetic medicinal chemistry, and pharmacokinetics. Dr. Hevener's collaborators on this work include Julian Hurdle, PhD, at Texas A&M Health Science Center, and Dianqing Sun, PhD, at the University of Hawaiʻi at Hilo.

This research is expected to provide new insights into treating CDI and advance FabK inhibitors as a new strategy for preventing and treating this serious infection.

"My team and I are thrilled to receive this NIH award," Dr. Hevener said. "It will help us develop new, narrow-spectrum treatments for C. difficile infections that prevent recurrence and allow the restoration of a healthy gut flora. I'm grateful to past and present members of my laboratory, my collaborators, and consultants for their hard work and support that made this possible."