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. Author manuscript; available in PMC: 2011 Nov 24.
Published in final edited form as: Chem Biol. 2010 Nov 24;17(11):1201–1211. doi: 10.1016/j.chembiol.2010.09.011

Figure 5. TcdB CPD inhibitors block holotoxin function.

Figure 5

(A) Primary human foreskin fibroblasts (HFFs) pretreated with Hpa-SL-AOMK are protected from holotoxin-mediated cell rounding. HFFs treated with the catalytically inactivated C698A holotoxin or left untreated exhibit minimal cell rounding.

(B) Quantification of inhibitor effects on holotoxin-mediated HFF cell rounding. Pre-treatment with Hpa-SL-AOMK or Hpa-KL-AOMK was protective, while Cbz-EL-AOMK and the pan-cathepsin inhibitor JPM-OEt had no effect on toxin function. Data represents the mean of three experiments ± standard deviation.

(C) Addition of wildtype TcdB holotoxin to HFFs results in complete glucosylation of the Rho GTPase Rac1, as seen by Western blot with the glucosylation-sensitive α-Rac1 monoclonal antibody mAb102. Pre-treating the cells with Hpa-SL-AOMK or Hpa-KL-AOMK protected HFFs from toxin effector domain activity, while inhibiting cathepsin activity with JPM-OEt did not.

See also Figure S3.