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Chlamydia trachomatis-containing vacuole serves as deubiquitination platform to stabilize Mcl-1 and to interfere with host defense.

Annette Fischer | Kelly S Harrison | Yesid Ramirez | Daniela Auer | Suvagata Roy Chowdhury | Bhupesh K Prusty | Florian Sauer | Zoe Dimond | Caroline Kisker | P Scott Hefty | Thomas Rudel
eLife | 2017

Obligate intracellular Chlamydia trachomatis replicate in a membrane-bound vacuole called inclusion, which serves as a signaling interface with the host cell. Here, we show that the chlamydial deubiquitinating enzyme (Cdu) 1 localizes in the inclusion membrane and faces the cytosol with the active deubiquitinating enzyme domain. The structure of this domain revealed high similarity to mammalian deubiquitinases with a unique α-helix close to the substrate-binding pocket. We identified the apoptosis regulator Mcl-1 as a target that interacts with Cdu1 and is stabilized by deubiquitination at the chlamydial inclusion. A chlamydial transposon insertion mutant in the Cdu1-encoding gene exhibited increased Mcl-1 and inclusion ubiquitination and reduced Mcl-1 stabilization. Additionally, inactivation of Cdu1 led to increased sensitivity of C. trachomatis for IFNγ and impaired infection in mice. Thus, the chlamydial inclusion serves as an enriched site for a deubiquitinating activity exerting a function in selective stabilization of host proteins and protection from host defense.

Pubmed ID: 28347402

Research resources used in this publication

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: P20 GM103638
  • Agency: NIGMS NIH HHS, United States
    Id: P20 GM113117
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI125929

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

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