Utilization of a CRISPRi-based <i>ex vivo</i> challenge model to reveal temporally dependent gene essentiality in intracellular <i>Mycobacterium tuberculosis</i>
. IMPORTANCE: model exploiting single-cell suspensions from Mtb-infected mouse lung homogenates to identify genes critical for intracellular survival at different time points in the infection continuum. This novel approach enabled us to identify how different bacterial metabolic pathways were of greater importance to the bacterium at different time points post-infection. The results provide insights into how the evolving immune response to infection shapes the metabolic and replicative status of the bacterium. This information has significance in the design of therapeutic strategies toward cure.
Authors
- Davide Pisu (ORCID: https://orcid.org/0000-0001-5641-8877)
- Joshua B. Wallach
- Monique Theriault (ORCID: https://orcid.org/0000-0002-9502-3402)
- David G. Russell (ORCID: https://orcid.org/0000-0002-9748-750X)
- Gabrielle Lê-Bury (ORCID: https://orcid.org/0000-0002-4650-5990)
- Dirk Schnappinger
- Michael A. DeJesus (ORCID: https://orcid.org/0000-0003-3867-0299)
- Andrew I. Wong
- Jeremy M. Rock (ORCID: https://orcid.org/0000-0002-9310-951X)
- Bom Nae Rin Lee
- Shuqi Li
- Greana Kirukubar
Institutions
- Cornell University (US)
- New York State College of Veterinary Medicine (US)
- Weill Cornell Medicine (US)
- Rockefeller University (US)
Publication Details
- Journal
- mBio
- Published
- 2026-04-20
- DOI
- https://doi.org/10.1128/mbio.00610-26
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bill and Melinda Gates Foundation
- Rita Allen Foundation
- National Institute of Allergy and Infectious Diseases