The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for the bacteria to persist in mice
Open accessAbstract
The success of Mycobacterium tuberculosis (Mtb) as a human pathogen relies on its ability to resist eradication by the immune system. The identification of mechanisms that enable Mtb to persist is key for finding ways to limit latent tuberculosis, which affects one-third of the world's population. Here we show that conditional gene silencing can be used to determine whether an Mtb gene required for optimal growth in vitro is also important for virulence and, if so, during which phase of an infection it is required. Application of this approach to the prcBA genes, which encode the core of the mycobacterial proteasome, revealed an unpredicted requirement of the core proteasome for the persistence of Mtb during the chronic phase of infection in mice. Proteasome depletion also attenuated Mtb in interferon-γ–deficient mice, pointing to a function of the proteasome beyond defense against the adaptive immune response. Genes that are essential for growth in vitro, in vivo or both account for approximately 20% of Mtb's genome. Conditional gene silencing could therefore facilitate the validation of up to 800 potential Mtb drug targets and improve our understanding of host-pathogen dynamics.
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The Growing Burden of Tuberculosis: Global Trends and Interactions With the HIV Epidemic
Corbett, E. L., Watt, C. J., Walker, N., Maher, D., Williams, B. G., Raviglione, M. C., & Dye, C. (2003) · Archives of Internal Medicine · doi:10.1001/archinte.163.9.1009 · Cited by 2,553
Genes required for mycobacterial growth defined by high density mutagenesis
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Genetic requirements for mycobacterial survival during infection
Sassetti, C. M., & Rubin, E. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2134250100 · Cited by 1,354
Proteasomes and their kin: proteases in the machine age
Pickart, C. M., & Cohen, R. E. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1336 · Cited by 735
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The Proteasome of Mycobacterium tuberculosis Is Required for Resistance to Nitric Oxide
Darwin, K. H., Ehrt, S., Gutierrez-Ramos, J.-C., Weich, N., & Nathan, C. F. (2003) · Science · doi:10.1126/science.1091176 · Cited by 535
Self-citation
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Gengenbacher, M., & Kaufmann, S. H. E. (2012) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2012.00331.x · Cited by 696
Proteasome Inhibitors: An Expanding Army Attacking a Unique Target
Kisselev, A. F., van der Linden, W. A., & Overkleeft, H. S. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.01.003 · Cited by 527
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Ehrt, S., & Schnappinger, D. (2009) · Cellular Microbiology · doi:10.1111/j.1462-5822.2009.01335.x · Cited by 448
Self-citationGenome-wide gene expression tuning reveals diverse vulnerabilities of M. tuberculosis
Bosch, B., DeJesus, M. A., Poulton, N. C., Zhang, W., Engelhart, C. A., Zaveri, A., Lavalette, S., Ruecker, N., Trujillo, C., Wallach, J. B., et al. (2021) · Cell · doi:10.1016/j.cell.2021.06.033 · Cited by 316
Self-citationMarrero, J., Rhee, K. Y., Schnappinger, D., Pethe, K., & Ehrt, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000715107 · Cited by 347
Self-citationBacterial proteases, untapped antimicrobial drug targets
Culp, E., & Wright, G. D. (2017) · The Journal of Antibiotics · doi:10.1038/ja.2016.138 · Cited by 244
Shiloh, M. U., & DiGiuseppe Champion, P. A. (2010) · Current Opinion in Microbiology · doi:10.1016/j.mib.2009.11.006 · Cited by 137
Metadata
- Authors
- Gandotra, S., Schnappinger, D., Monteleone, M., Hillen, W., & Ehrt, S.
- Venue
- Nature Medicine
- Published
- 2007-12
- Volume
- 13
- Issue
- 12
- Pages
- 1515-1520
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2065542724
- Cited by
- 254
- References
- 34
- FWCI
- 10.77
- Type
- journal article
- Language
- en
- Open access
- green
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