Treatment of infected cells with pan-caspase inhibitor IV and Z-WEHD-FMK, an inhibitor of inflammatory caspases, elicited a near-complete blockage of C. trachomatis-induced cleavage of golgin-84. Golgin-84 cleavage was blocked via treatment of infected cells with Z-WEHD-FMK, resulting in a lack of Golgi fragmentation and a 2-log reduction in numbers of infectious bacteria.
We treated infected cells with Z-WEHD-FMK, effectively preventing Golgi fragmentation, or with DMSO as a control and then labelled cells with fluorescent ceramide. Confocal images revealed that ceramide was rapidly incorporated into the inclusion membrane within DMSO-treated cells and accumulated inside the inclusion in bacterial membranes. In contrast, Z-WEHD-FMK-treated cells were only slightly fluorescent as the majority of lipid accumulated in a Golgi-like structure outside the inclusion1.
General caspase inhibitor (Z-Asp-CHz-DCB) and capase-5 inhibitor (Z-WEHD-FMK) could not induce rRNA fragmentation treated with ECyd. Caspase-5 (ICErei Ill/TY), member of ICE protease, activated pathway may be concerned with ECyd induced rRNA fragmentation2.
References:
1. D. Heuer, A.R. Lipinski et al. Chlamydia causes fragmentation of the Golgi compartment to ensure reproduction. NATURE, 457, 2009
2. Kamada, S., Funahashi, Y. and Tsujimoto, Y.(1997) Cell Death Diff. 4, 473-478.