National Institute of Allergy and Infectious Diseases 1R01AI198244-01

Clostridiodes difficile spore germination and therapeutic intervention

This award funds research to understand and inhibit Clostridioides difficile spore germination to prevent recurrent infections, aiming to develop new antibiotics and therapeutic interventions.

Description

Clostridioides difficile infections (CDIs) are difficult to treat, resulting in approximately 11,500 deaths in the United States every year. A challenge in treating CDI is the production of spores that germinate to vegetative cells, which cause the infection. Recurrence of infection occurs in 25% of patients. There are no antibiotics for the treatment of recurrent CDI. CDI is the deadliest of the five bacterial urgent threats. Understanding the process of spore germination is key to elucidating the basis for recurrent CDI. If spore germination could be prevented, the nefarious cycles of CDI will be interrupted, which will save lives. We disclose the discovery of a new class of antibiotics (the oxadiazoles) that kill C. difficile in the growing phase (vegetative cells). We also have found that certain oxadiazoles inhibit spore germination. Our goals are to elucidate the spore-germination pathway and to discover new and more effective oxadiazoles that inhibit spore germination in clinical settings.

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