Project Grant F32AI197474

Federal Project Grant Award Summary

The National Institute of Allergy and Infectious Diseases (NIAID) awarded Tufts University School of Medicine a $227,640 Project Grant under the Allergy and Infectious Diseases Research program (CFDA 93.855) on September 30, 2026, with completion anticipated by March 29, 2029. The award funds research into the molecular mechanisms regulating amidase activity during bacterial spore development in Clostridioides difficile, a significant pathogenic organism. The research employs genetic, biochemical, and structural approaches to elucidate three critical areas: the allosteric activation circuit controlling zinc cofactor binding in the CWLD amidase enzyme, the mechanisms governing CWLD localization during forespore development, and the impact of CWLD on cortex synthesis and coat assembly. Understanding these regulatory pathways has direct implications for understanding spore germination and disease initiation in clostridial pathogens.

The project deliverables include experimental findings and peer-reviewed scientific publications documenting the conformational changes induced by GERS (a regulatory lipoprotein) binding to CWLD, the identification of key regulatory regions controlling zinc binding, and clarification of the localization signals that position CWLD around the developing forespore. These outputs advance fundamental knowledge of bacterial spore biology and may inform the development of novel antimicrobial strategies targeting spore-forming pathogens of public health importance.