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Chlamydia trachomatis prevents apoptosis via activation of PDPK1-MYC and enhanced mitochondrial binding of hexokinase II

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Item Type:Article
Title:Chlamydia trachomatis prevents apoptosis via activation of PDPK1-MYC and enhanced mitochondrial binding of hexokinase II
Creators Name:Al-Zeer, M.A. and Xavier, A. and Abu Lubad, M. and Sigulla, J. and Kessler, M. and Hurwitz, R. and Meyer, T.F.
Abstract:The intracellular human bacterial pathogen Chlamydia trachomatis pursues effective strategies to protect infected cells against death-inducing stimuli. Here, we show that Chlamydia trachomatis infection evokes 3-phosphoinositide-dependent protein kinase-1 (PDPK1) signaling to ensure the completion of its developmental cycle, further leading to the phosphorylation and stabilization of MYC. Using biochemical approaches and imaging we demonstrate that Chlamydia-induced PDPK1-MYC signaling induces host hexokinase II (HKII), which becomes enriched and translocated to the mitochondria. Strikingly, preventing the HKII interaction with mitochondria using exogenous peptides triggers apoptosis of infected cells as does inhibiting either PDPK1 or MYC, which also disrupts intracellular development of Chlamydia trachomatis. These findings identify a previously unknown pathway activated by Chlamydia infection, which exhibits pro-carcinogenic features. Targeting the PDPK1-MYC-HKII-axis may provide a strategy to overcome therapeutic resistance of infection.
Keywords:Warburg Effect, PDPK1, Host-Pathogen Interaction, Metabolism, MYC
Source:EBioMedicine
ISSN:2352-3964
Publisher:Elsevier (The Netherlands)
Volume:23
Page Range:100-110
Date:September 2017
Official Publication:https://doi.org/10.1016/j.ebiom.2017.08.005
PubMed:View item in PubMed

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