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Toxins 2015, 7(2), 621-637; doi:10.3390/toxins7020621

DXD Motif-Dependent and -Independent Effects of the Chlamydia trachomatis Cytotoxin CT166

1
Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany
2
Institute for Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Michel R. Popoff
Received: 19 December 2014 / Revised: 14 January 2015 / Accepted: 10 February 2015 / Published: 17 February 2015
(This article belongs to the Section Animal Venoms)
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Abstract

The Gram-negative, intracellular bacterium Chlamydia trachomatis causes acute and chronic urogenital tract infection, potentially leading to infertility and ectopic pregnancy. The only partially characterized cytotoxin CT166 of serovar D exhibits a DXD motif, which is important for the enzymatic activity of many bacterial and mammalian type A glycosyltransferases, leading to the hypothesis that CT166 possess glycosyltransferase activity. CT166-expressing HeLa cells exhibit actin reorganization, including cell rounding, which has been attributed to the inhibition of the Rho-GTPases Rac/Cdc42. Exploiting the glycosylation-sensitive Ras(27H5) antibody, we here show that CT166 induces an epitope change in Ras, resulting in inhibited ERK and PI3K signaling and delayed cell cycle progression. Consistent with the hypothesis that these effects strictly depend on the DXD motif, CT166 with the mutated DXD motif causes neither Ras-ERK inhibition nor delayed cell cycle progression. In contrast, CT166 with the mutated DXD motif is still capable of inhibiting cell migration, suggesting that CT166 with the mutated DXD motif cannot be regarded as inactive in any case. Taken together, CT166 affects various fundamental cellular processes, strongly suggesting its importance for the intracellular survival of chlamydia. View Full-Text
Keywords: chlamydia, glycosyltransferase; Clostridium difficile toxin B; Clostridium sordellii lethal toxin; Ras; Rho chlamydia, glycosyltransferase; Clostridium difficile toxin B; Clostridium sordellii lethal toxin; Ras; Rho
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Bothe, M.; Dutow, P.; Pich, A.; Genth, H.; Klos, A. DXD Motif-Dependent and -Independent Effects of the Chlamydia trachomatis Cytotoxin CT166. Toxins 2015, 7, 621-637.

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