title: Tumor suppressor p53 alters host cell metabolism to limit Chlamydia trachomatis infection.
abstract: Obligate intracellular bacteria depend entirely on nutrients from the host cell for their reproduction. Here, we show that obligate intracellular Chlamydia downregulate the central tumor suppressor p53 in human cells. This reduction of p53 levels is mediated by the PI3K-Akt signaling pathway, activation of HDM2, and subsequent proteasomal degradation of p53. The stabilization of p53 in human cells severely impaired chlamydial development and caused the loss of infectious particle formation. DNA-damage-induced p53 interfered with chlamydial development through downregulation of the pentose phosphate pathway (PPP). Increased expression of the PPP key enzyme glucose-6-phosphate dehydrogenase rescued the inhibition of chlamydial growth induced by DNA damage or stabilized p53. Thus, downregulation of p53 is a key event in the chlamydial life cycle that reprograms the host cell to create a metabolic environment supportive of chlamydial growth.
authors.affiliation: Department of Microbiology, University of Würzburg Biocenter, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Siegl
authors.affiliation: Department of Microbiology, University of Würzburg Biocenter, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Bhupesh K
authors.initials: BK
authors.lastname: Prusty
authors.affiliation: Department of Microbiology, University of Würzburg Biocenter, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Karthika
authors.initials: K
authors.lastname: Karunakaran
authors.affiliation: Frauenklinik, University Clinic Würzburg, Josef-Schneider-Str. 4, 97080 Würzburg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Wischhusen
authors.affiliation: Department of Microbiology, University of Würzburg Biocenter, Am Hubland, 97074 Würzburg, Germany. Electronic address: thomas.rudel@biozentrum.uni-wuerzburg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rudel
mesh_terms: D000818:Animals; D016923:Cell Death; D002690:Chlamydia Infections / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D002692:Chlamydia trachomatis / Q000502:physiology*; D004260:DNA Repair; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006019:Glycolysis; D054884:Host-Pathogen Interactions; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D055550:Protein Stability; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D005954:Glucosephosphate Dehydrogenase; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D019869:Phosphatidylinositol 3-Kinases