Clostridioides difficile (C. diff) is a leading cause of hospital-acquired infection and diarrhea. C. diff infection requires the secretion of one or more bacterial toxins. Recent studies have suggested that the C. diff transferase toxin (CDT) increases the severity of infection.
To explore how CDT functions, D. Borden Lacy, PhD, and colleagues used cryo-electron microscopy to define the structure of the cell-binding component of CDT. The investigators identified four distinct CDT structural states and developed a model for the conformational changes in CDT as it forms a membrane pore.
The analysis revealed a previously unknown toxin domain and pinpointed the parts of the toxin involved in binding to the host cell receptor.
The findings, reported in the January issue of Nature Microbiology, provide a framework for understanding CDT function and may aid the design of novel therapeutics that block CDT to treat C. diff infections.
This research was supported by the U.S. Department of Veterans Affairs (award BX002943), the National Institutes of Health (grant AI095755) and Vanderbilt University.
