Loading…

Chlamydia trachomatis Prevents Apoptosis Via Activation of PDPK1-MYC and Enhanced Mitochondrial Binding of Hexokinase II

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 o...

Full description

Saved in:
Bibliographic Details
Published in:EBioMedicine 2017-09, Vol.23 (C), p.100-110
Main Authors: Al-Zeer, Munir A., Xavier, Audrey, Abu Lubad, Mohammad, Sigulla, Janine, Kessler, Mirjana, Hurwitz, Robert, Meyer, Thomas F.
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. •MYC oncogene expression is induced and stabilized in Chlamydia-infected cells via activation of PDPK1.•Activation of the PDPK1-MYC axis enhances hexokinase II expression.•HKII-mitochondria association prevents apoptosis to support chlamydial growth. Activation of oncogenes promotes cell survival and metabolic reprogramming. Intracellular pathogens target oncogenes to exploit cellular machineries and inhibit apoptosis. Al-Zeer et al. now highlight the role of the oncogene MYC for inducing hexokinase II activation during Chlamydia infection, linking cell survival to energy metabolism.
ISSN:2352-3964
2352-3964
DOI:10.1016/j.ebiom.2017.08.005