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

Publication ,  Journal Article
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 in: Cell Host Microbe
December 14, 2022

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.

Duke Scholars

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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

December 14, 2022

Volume

30

Issue

12

Start / End Page

1671 / 1684.e9

Location

United States

Related Subject Headings

  • Ubiquitins
  • Ubiquitination
  • Ubiquitin-Protein Ligases
  • Interferon-gamma
  • Immunology
  • Humans
  • Hela Cells
  • HeLa Cells
  • Genome-Wide Association Study
  • Female
 

Citation

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Walsh, S. C., Reitano, J. R., Dickinson, M. S., Kutsch, M., Hernandez, D., Barnes, A. B., … Coers, J. (2022). The bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction. Cell Host Microbe, 30(12), 1671-1684.e9. https://doi.org/10.1016/j.chom.2022.08.008
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

December 14, 2022

Volume

30

Issue

12

Start / End Page

1671 / 1684.e9

Location

United States

Related Subject Headings

  • Ubiquitins
  • Ubiquitination
  • Ubiquitin-Protein Ligases
  • Interferon-gamma
  • Immunology
  • Humans
  • Hela Cells
  • HeLa Cells
  • Genome-Wide Association Study
  • Female