title: DXD motif-dependent and -independent effects of the chlamydia trachomatis cytotoxin CT166.
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.
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. bothe.miriam@mh-hannover.de.
authors.forename: Miriam
authors.initials: M
authors.lastname: Bothe
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. dutow.pavel@mh-hannover.de.
authors.forename: Pavel
authors.initials: P
authors.lastname: Dutow
authors.affiliation: Institute for Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. pich.andreas@mh-hannover.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pich
authors.affiliation: Institute for Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. genth.harald@mh-hannover.de.
authors.forename: Harald
authors.initials: H
authors.lastname: Genth
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. klos.andreas@mh-hannover.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Klos
mesh_terms: D020816:Amino Acid Motifs; D002453:Cell Cycle / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002692:Chlamydia trachomatis / Q000201:enzymology* / Q000254:growth & development; D003603:Cytotoxins / Q000235:genetics / Q000502:physiology*; D005964:Glucosyltransferases / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D009154:Mutation; D014162:Transfection; D018631:ras Proteins / Q000037:antagonists & inhibitors
chemical_list: D003603:Cytotoxins; C554842:CT166 protein, Chlamydia trachomatis; D005964:Glucosyltransferases; D018631:ras Proteins