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Chlamydia infection depends on a functional MDM2-p53 axis

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Item Type:Article
Title:Chlamydia infection depends on a functional MDM2-p53 axis
Creators Name:Gonzalez, E. and Rother, M. and Kerr, M.C. and Al-Zeer, M.A. and Abu-Lubad, M. and Kessler, M. and Brinkmann, V. and Loewer, A. and Meyer, T.F.
Abstract:Chlamydia, a major human bacterial pathogen, assumes effective strategies to protect infected cells against death-inducing stimuli, thereby ensuring completion of its developmental cycle. Paired with its capacity to cause extensive host DNA damage, this poses a potential risk of malignant transformation, consistent with circumstantial epidemiological evidence. Here we reveal a dramatic depletion of p53, a tumor suppressor deregulated in many cancers, during Chlamydia infection. Using biochemical approaches and live imaging of individual cells, we demonstrate that p53 diminution requires phosphorylation of Murine Double Minute 2 (MDM2; a ubiquitin ligase) and subsequent interaction of phospho-MDM2 with p53 before induced proteasomal degradation. Strikingly, inhibition of the p53-MDM2 interaction is sufficient to disrupt intracellular development of Chlamydia and interferes with the pathogen's anti-apoptotic effect on host cells. This highlights the dependency of the pathogen on a functional MDM2-p53 axis and lends support to a potentially pro-carcinogenic effect of chlamydial infection.
Keywords:Apoptosis, Chlamydia, Chlamydia Infections, Chlamydia trachomatis, HeLa Cells, Neoplastic Cell Transformation, Phosphorylation, Proto-Oncogene Proteins c-mdm2, Tumor Suppressor Protein p53, Western Blotting
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:5
Page Range:5201
Date:13 November 2014
Official Publication:https://doi.org/10.1038/ncomms6201
PubMed:View item in PubMed

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