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Tumor Suppressor p53 Alters Host Cell Metabolism to Limit Chlamydia trachomatis Infection

Please always quote using this URN: urn:nbn:de:bvb:20-opus-118200
  • 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 chlamydialObligate 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.show moreshow less

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Metadaten
Author: Christine Siegl, Bhupesh K. Prusty, Karthika Karunakaran, Jörg Wischhusen, Thomas Rudel
URN:urn:nbn:de:bvb:20-opus-118200
Document Type:Journal article
Faculties:Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Cell Reports
ISSN:2211-1247
Year of Completion:2014
Volume:9
Issue:3
Pagenumber:918–929
Source:Cell Reports 9, 918–929. DOI:10.1016/j.celrep.2014.10.004
DOI:https://doi.org/10.1016/j.celrep.2014.10.004
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=25437549
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:chlamydia trachomatis; tumor
Release Date:2015/09/04
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitung