Clostridioides difficile (C. difficile) produces TcdB, essential for its virulence and the pathogenesis of the infection it causes. TcdB, a large protein, functions by hijacking host cell processes, leading to severe colonic inflammation and tissue damage. Different variants of TcdB (specifically TcdB1 and TcdB2) have different cell-binding properties due to variations in their amino acid sequences. Understanding these differences in cell tropism is crucial for grasping the variations in the impact and progression of C. difficile infections. Research has delved into the role of calcium (Ca2+) in the interaction of TcdB variants with cells, focusing on how Ca2+ influences TcdB’s receptor preferences and toxicity. The study discovered that TcdB favors binding to CSPG4 over FZD proteins in the presence of Ca2+. This preference is linked to Ca2+’s ability to enhance TcdB’s interaction with CSPG4. Moreover, the research showed that chondroitin sulfate, a key component of CSPG4, is crucial for TcdB’s entry into cells. These findings illuminate the complex dynamics of TcdB’s interaction with host cells and reveal how external factors like calcium levels can significantly influence the course of C. difficile infection.
Reference: Doyle DA, DeAngelis PL, Ballard JD. CSPG4-dependent cytotoxicity for C. difficile TcdB is influenced by extracellular calcium and chondroitin sulfate. mSphere. 2024 Mar 12:e0009424. doi: 10.1128/msphere.00094-24. Epub ahead of print. PMID: 38470254.
