TABLE 6.
Host cell factors that mediate cell surface binding and internalization of LCTs
| Host cell factora | Binding regionb | Expression in human tissuec | PDBd |
|---|---|---|---|
| TcdA | |||
| Sulfated glycosaminoglycans (sGAGs) (148) | 1–1832 (148) | Colonic epithelium (148) | NA |
| Low-density lipoprotein receptor (LDLR) (148) | 1–1832 (148) | ND | NA |
| Low-density lipoprotein receptor-related protein-1 (LRP1) (174) | ND | ND | NA |
| TcdB | |||
| Chondroitin sulfate proteoglycan 4 (CSPG4) (155) | 1500–1850 (154) | Multinucleated intestinal subepithelial myofibroblasts (179) | NA |
| Frizzled family receptors (FZD)1/2/7 (156) | Discontinuous surface, 1433–1599 (170) | Colonic epithelium (156) | 6C0B |
| Poliovirus receptor-like protein 3 (PVRL3) (157) | 1372–1493 (162) | Colonic epithelium (157) | NA |
| TcsL | |||
| Semaphorins (SEMA)6A/6B (158, 159) | Discontinuous surface, 1433–1601 (158) | Vascular endothelium (158, 159) | 6WTS |
| TpeL | |||
| LRP1 (160) | 1335–1779 (160) | ND | NA |
aLCTs are from the following strains: C. difficile VPI 10463, P. sordellii JGS6382 and 6018, and C. perfringens JGS1495. Under new subtyping analysis, TcdA and TcdB from C. difficile VPI 10463 are referred to as TcdA1 and TcdB1 (138). Sucrase isomaltase (275) and glycoprotein 96 (Gp96) (276) have also been identified as TcdA receptors, but their lack of expression on the intestinal epithelial cells makes their physiological relevance to C. difficile pathogenesis unclear.
bBinding region indicates the minimal region demonstrated to bind to the receptor or the stretch of LCT interface residues that bind to the receptor, as determined from the LCT-receptor complex. ND, not determined if the full-length LCT was used to detect binding.
cIncludes human tissues that are physiologically relevant for infection. ND, not determined.
d NA, not available.