3-D structure of C. difficile toxin engaged with CSPG4 receptor. (IMAGE)
Caption
Clostridioides difficile (C. difficile) is classified as an urgent antibiotic resistance threat by the CDC. The 3-D structure shows how a key C. difficile toxin, TcdB (grey surface model), engages the human receptor CSPG4 (shown in green) for cell entry, and how an FDA-approved therapeutic antibody bezlotoxumab (shown in blue and purple) recognize two epitopes on TcdB. Some C. difficile hypervirulent strains evolve mutations in the bezlotoxumab-binding sites (blue and purple surface, while the mutated amino acids are colored red) that weaken the antibody potency. In contrast, the CSPG4-binding site on TcdB (gold surface) is highly conserved, suggesting a strategy to develop broad-spectrum therapeutics against TcdB.
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UCI School of Medicine
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