Related Content
Search Google Scholar for:
More Information
Related Jobs from ScienceCareers
|
|
Science 12 December 2003:
Vol. 302. no. 5652, pp. 1963 - 1966
DOI: 10.1126/science.1091176
|
|
Reports
The Proteasome of Mycobacterium tuberculosis Is Required for Resistance to Nitric Oxide
K. Heran Darwin,1
Sabine Ehrt,1
José-Carlos Gutierrez-Ramos,2
Nadine Weich,2
Carl F. Nathan1,3*
The production of nitric oxide and other reactive nitrogen intermediates (RNI) by macrophages helps to control infection by Mycobacterium tuberculosis (Mtb). However, the protection is imperfect and infection persists. To identify genes that Mtb requires to resist RNI, we screened 10,100 Mtb transposon mutants for hypersusceptibility to acidified nitrite. We found 12 mutants with insertions in seven genes representing six pathways, including the repair of DNA (uvrB) and the synthesis of a flavin cofactor (fbiC). Five mutants had insertions in proteasome-associated genes. An Mtb mutant deficient in a presumptive proteasomal adenosine triphosphatase was attenuated in mice, and exposure to proteasomal protease inhibitors markedly sensitized wild-type Mtb to RNI. Thus, the mycobacterial proteasome serves as a defense against oxidative or nitrosative stress.
1 Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
2 Millennium Pharmaceuticals, 75 Sidney Street, Cambridge, MA 02139, USA.
3 Programs in Immunology and Molecular Biology, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA.
* To whom correspondence should be addressed. E-mail: cnathan{at}med.cornell.edu
Read the Full Text
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
- Regulation of the SigH stress response regulon by an essential protein kinase in Mycobacterium tuberculosis.
- S. T. Park, C.-M. Kang, and R. N. Husson (2008)
PNAS
105, 13105-13110
| Abstract »
| Full Text »
| PDF »
- Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents.
- K. Kurthkoti, P. Kumar, R. Jain, and U. Varshney (2008)
Microbiology
154, 2776-2785
| Abstract »
| Full Text »
| PDF »
- Crystal Structures of F420-dependent Glucose-6-phosphate Dehydrogenase FGD1 Involved in the Activation of the Anti-tuberculosis Drug Candidate PA-824 Reveal the Basis of Coenzyme and Substrate Binding.
- G. Bashiri, C. J. Squire, N. J. Moreland, and E. N. Baker (2008)
J. Biol. Chem.
283, 17531-17541
| Abstract »
| Full Text »
| PDF »
- Mycobacterial persistence requires the utilization of host cholesterol.
- A. K. Pandey and C. M. Sassetti (2008)
PNAS
105, 4376-4380
| Abstract »
| Full Text »
| PDF »
- Genetic and Proteomic Analyses of a Proteasome-Activating Nucleotidase A Mutant of the Haloarchaeon Haloferax volcanii.
- P. A. Kirkland, M. A. Gil, I. M. Karadzic, and J. A. Maupin-Furlow (2008)
J. Bacteriol.
190, 193-205
| Abstract »
| Full Text »
| PDF »
- Mycobacterium smegmatis mc2 155 fbiC and MSMEG_2392 are involved in triphenylmethane dye decolorization and coenzyme F420 biosynthesis.
- D. Guerra-Lopez, L. Daniels, and M. Rawat (2007)
Microbiology
153, 2724-2732
| Abstract »
| Full Text »
| PDF »
- A Genetic Screen for Mycobacterium tuberculosis Mutants Defective for Phagosome Maturation Arrest Identifies Components of the ESX-1 Secretion System.
- J. A. MacGurn and J. S. Cox (2007)
Infect. Immun.
75, 2668-2678
| Abstract »
| Full Text »
| PDF »
- Genome-Wide Identification of Francisella tularensis Virulence Determinants.
- J. Su, J. Yang, D. Zhao, T. H. Kawula, J. A. Banas, and J.-R. Zhang (2007)
Infect. Immun.
75, 3089-3101
| Abstract »
| Full Text »
| PDF »
- Characterization of the Proteasome Accessory Factor (paf) Operon in Mycobacterium tuberculosis.
- R. A. Festa, M. J. Pearce, and K. H. Darwin (2007)
J. Bacteriol.
189, 3044-3050
| Abstract »
| Full Text »
| PDF »
- Characterization of the Helicase Activity and Substrate Specificity of Mycobacterium tuberculosis UvrD.
- E. Curti, S. J. Smerdon, and E. O. Davis (2007)
J. Bacteriol.
189, 1542-1555
| Abstract »
| Full Text »
| PDF »
- A Mycobacterium marinum mel2 Mutant Is Defective for Growth in Macrophages That Produce Reactive Oxygen and Reactive Nitrogen Species.
- S. Subbian, P. K. Mehta, S. L. G. Cirillo, L. E. Bermudez, and J. D. Cirillo (2007)
Infect. Immun.
75, 127-134
| Abstract »
| Full Text »
| PDF »
- Dihydrolipoamide Acyltransferase Is Critical for Mycobacterium tuberculosis Pathogenesis.
- S. Shi and S. Ehrt (2006)
Infect. Immun.
74, 56-63
| Abstract »
| Full Text »
| PDF »
- Identification of Histoplasma capsulatum Transcripts Induced in Response to Reactive Nitrogen Species.
- M. P. Nittler, D. Hocking-Murray, C. K. Foo, and A. Sil (2005)
Mol. Biol. Cell
16, 4792-4813
| Abstract »
| Full Text »
| PDF »
- Inactivation of the 20S proteasome in Streptomyces lividans and its influence on the production of heterologous proteins.
- B. Hong, L. Wang, E. Lammertyn, N. Geukens, L. Van Mellaert, Y. Li, and J. Anne (2005)
Microbiology
151, 3137-3145
| Abstract »
| Full Text »
| PDF »
- Role for Nucleotide Excision Repair in Virulence of Mycobacterium tuberculosis.
- K. H. Darwin and C. F. Nathan (2005)
Infect. Immun.
73, 4581-4587
| Abstract »
| Full Text »
| PDF »
- S-nitroso proteome of Mycobacterium tuberculosis: Enzymes of intermediary metabolism and antioxidant defense.
- K. Y. Rhee, H. Erdjument-Bromage, P. Tempst, and C. F. Nathan (2005)
PNAS
102, 467-472
| Abstract »
| Full Text »
| PDF »
- Identification of Mycobacterium tuberculosis Counterimmune (cim) Mutants in Immunodeficient Mice by Differential Screening.
- K. B. Hisert, M. A. Kirksey, J. E. Gomez, A. O. Sousa, J. S. Cox, W. R. Jacobs Jr., C. F. Nathan, and J. D. McKinney (2004)
Infect. Immun.
72, 5315-5321
| Abstract »
| Full Text »
| PDF »
- Mechanisms of Resistance to Oxidative and Nitrosative Stress: Implications for Fungal Survival in Mammalian Hosts.
- T. A. Missall, J. K. Lodge, and J. E. McEwen (2004)
Eukaryot. Cell
3, 835-846
| Full Text »
| PDF »
|
|
