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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.

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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
Walsh, Stephen C., Jeffrey R. Reitano, Mary S. Dickinson, Miriam Kutsch, Dulcemaria Hernandez, Alyson B. Barnes, Benjamin H. Schott, et al. “The bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction.Cell Host Microbe 30, no. 12 (December 14, 2022): 1671-1684.e9. https://doi.org/10.1016/j.chom.2022.08.008.
Walsh SC, Reitano JR, Dickinson MS, Kutsch M, Hernandez D, Barnes AB, et al. The bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction. Cell Host Microbe. 2022 Dec 14;30(12):1671-1684.e9.
Walsh, Stephen C., et al. “The bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction.Cell Host Microbe, vol. 30, no. 12, Dec. 2022, pp. 1671-1684.e9. Pubmed, doi:10.1016/j.chom.2022.08.008.
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. The bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction. Cell Host Microbe. 2022 Dec 14;30(12):1671-1684.e9.
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