The bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction.

Journal Article (Journal Article)

Chlamydia trachomatis is the leading cause of sexually transmitted bacterial infections and a major threat to women's reproductive health in particular. This obligate intracellular pathogen resides and replicates within a cellular compartment termed an inclusion, where it is sheltered by unknown mechanisms from gamma-interferon (IFNγ)-induced cell-autonomous host immunity. Through a genetic screen, we uncovered the Chlamydia inclusion membrane protein gamma resistance determinant (GarD) as a bacterial factor protecting inclusions from cell-autonomous immunity. In IFNγ-primed human cells, inclusions formed by garD loss-of-function mutants become decorated with linear ubiquitin and are eliminated. Leveraging cellular genome-wide association data, we identified the ubiquitin E3 ligase RNF213 as a candidate anti-Chlamydia protein. We demonstrate that IFNγ-inducible RNF213 facilitates the ubiquitylation and destruction of GarD-deficient inclusions. Furthermore, we show that GarD operates as a cis-acting stealth factor barring RNF213 from targeting inclusions, thus functionally defining GarD as an RNF213 antagonist essential for chlamydial growth during IFNγ-stimulated immunity.

Full Text

Duke Authors

Cited Authors

  • Walsh, SC; Reitano, JR; Dickinson, MS; Kutsch, M; Hernandez, D; Barnes, AB; Schott, BH; Wang, L; Ko, DC; Kim, SY; Valdivia, RH; Bastidas, RJ; Coers, J

Published Date

  • December 14, 2022

Published In

Volume / Issue

  • 30 / 12

Start / End Page

  • 1671 - 1684.e9

PubMed ID

  • 36084633

Pubmed Central ID

  • PMC9772000

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2022.08.008


  • eng

Conference Location

  • United States