Chlamydia infection depends on a functional MDM2-p53 axis

Erik González, Marion Rother, Markus C. Kerr, Munir A. Al-Zeer, Mohammad Abu-Lubad, Mirjana Kessler, Volker Brinkmann, Alexander Loewer and Thomas F. Meyer ()
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Erik González: Max Planck Institute for Infection Biology
Marion Rother: Max Planck Institute for Infection Biology
Markus C. Kerr: Max Planck Institute for Infection Biology
Munir A. Al-Zeer: Max Planck Institute for Infection Biology
Mohammad Abu-Lubad: Max Planck Institute for Infection Biology
Mirjana Kessler: Max Planck Institute for Infection Biology
Volker Brinkmann: Max Planck Institute for Infection Biology
Alexander Loewer: Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine
Thomas F. Meyer: Max Planck Institute for Infection Biology

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6201

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