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

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 act...

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Autores principales: Bothe, Miriam, Dutow, Pavel, Pich, Andreas, Genth, Harald, Klos, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344646/
https://www.ncbi.nlm.nih.gov/pubmed/25690695
http://dx.doi.org/10.3390/toxins7020621
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author Bothe, Miriam
Dutow, Pavel
Pich, Andreas
Genth, Harald
Klos, Andreas
author_facet Bothe, Miriam
Dutow, Pavel
Pich, Andreas
Genth, Harald
Klos, Andreas
author_sort Bothe, Miriam
collection PubMed
description 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.
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spelling pubmed-43446462015-03-18 DXD Motif-Dependent and -Independent Effects of the Chlamydia trachomatis Cytotoxin CT166 Bothe, Miriam Dutow, Pavel Pich, Andreas Genth, Harald Klos, Andreas Toxins (Basel) Article 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. MDPI 2015-02-17 /pmc/articles/PMC4344646/ /pubmed/25690695 http://dx.doi.org/10.3390/toxins7020621 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bothe, Miriam
Dutow, Pavel
Pich, Andreas
Genth, Harald
Klos, Andreas
DXD Motif-Dependent and -Independent Effects of the Chlamydia trachomatis Cytotoxin CT166
title DXD Motif-Dependent and -Independent Effects of the Chlamydia trachomatis Cytotoxin CT166
title_full DXD Motif-Dependent and -Independent Effects of the Chlamydia trachomatis Cytotoxin CT166
title_fullStr DXD Motif-Dependent and -Independent Effects of the Chlamydia trachomatis Cytotoxin CT166
title_full_unstemmed DXD Motif-Dependent and -Independent Effects of the Chlamydia trachomatis Cytotoxin CT166
title_short DXD Motif-Dependent and -Independent Effects of the Chlamydia trachomatis Cytotoxin CT166
title_sort dxd motif-dependent and -independent effects of the chlamydia trachomatis cytotoxin ct166
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344646/
https://www.ncbi.nlm.nih.gov/pubmed/25690695
http://dx.doi.org/10.3390/toxins7020621
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