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

EBioMedicine

Mirjana Kessler¹  Munir A. Al-Zeer¹  Janine Sigulla¹  Thomas F. Meyer¹  Mohammad Abu Lubad¹  Audrey Xavier¹  Robert Hurwitz² 

[1]Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany

[2]Protein Purification Core Facility, Max Planck Institute for Infection Biology, Berlin, Germany

关键词: Warburg effect;    PDPK1;    Host-pathogen interaction;    Metabolism;    MYC;   

DOI  :  10.1016/j.ebiom.2017.08.005

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown