The Chlamydia effector Dre1 binds dynactin to reposition host organelles during infection
The obligate intracellular pathogen Chlamydia trachomatis replicates in a specialized membrane-bound compartment where it repositions host organelles during infection to acquire nutrients and evade host surveillance. We describe a bacterial effector, Dre1, that binds specifically to dynactin associated with host microtubule organizing centers without globally impeding dynactin function. Dre1 is required to reposition the centrosome, mitotic spindle, Golgi apparatus, and primary cilia around the inclusion and contributes to pathogen fitness in cell-based and mouse models of infection. We utilized Dre1 to affinity purify the megadalton dynactin protein complex and determined the first cryoelectron microscopy (cryo-EM) structure of human dynactin. Our results suggest that Dre1 binds to the pointed end of dynactin and uncovers the first bacterial effector that modulates dynactin function. Our work highlights how a pathogen employs a single effector to evoke targeted, large-scale changes in host cell organization that facilitate pathogen growth without inhibiting host viability.
Authors
- Joanne N. Engel (ORCID: https://orcid.org/0000-0002-2168-9711)
- Jeffrey R. Johnson (ORCID: https://orcid.org/0000-0002-4221-298X)
- Lee Dolat (ORCID: https://orcid.org/0000-0003-1271-4863)
- Eleanor McMahon
- Raphael H. Valdivia (ORCID: https://orcid.org/0000-0003-0961-073X)
- Nevan J. Krogan (ORCID: https://orcid.org/0000-0003-4902-337X)
- Robyn M. Kaake (ORCID: https://orcid.org/0000-0002-8341-3067)
- Robert J. Bastidas (ORCID: https://orcid.org/0000-0001-9219-572X)
- Cherilyn A. Elwell (ORCID: https://orcid.org/0000-0001-7702-3938)
- Komal Ishwar Pawar (ORCID: https://orcid.org/0000-0002-1968-9851)
- I-Chang Chang
- Kliment A. Verba (ORCID: https://orcid.org/0000-0002-2238-8590)
- Erin P. Smith (ORCID: https://orcid.org/0000-0003-4822-476X)
- Jessica Sherry
- Danielle L. Swaney (ORCID: https://orcid.org/0000-0001-6119-6084)
- Khavong Pha
- Clara Herrera
Institutions
- University of California, San Francisco (US)
- Duke Medical Center (US)
- Duke University Hospital (US)
- University of San Francisco (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115509
- Primary Topic
- Reproductive tract infections research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- National Institutes of Health
- University of California, San Francisco
- Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases