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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Herrmann, Martin Niederweis, Michael Doornbos, Kathryn S. Sun, Jim Speer, Alexander Ehrt, Sabine Trujillo, Carolina Marrero, Joeli Muñoz, Luis E. Berens, Christian Pavlenok, Mikhail Siroy, Axel Maueröder, Christian Mayhew, David L. Danilchanka, Olga |
| Description | Author Affiliation: Danilchanka O ( Departments of Microbiology and Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35294.); |
| Abstract | The ability to control the timing and mode of host cell death plays a pivotal role in microbial infections. Many bacteria use toxins to kill host cells and evade immune responses. Such toxins are unknown in Mycobacterium tuberculosis. Virulent M. tuberculosis strains induce necrotic cell death in macrophages by an obscure molecular mechanism. Here we show that the M. tuberculosis protein Rv3903c (channel protein with necrosis-inducing toxin, CpnT) consists of an N-terminal channel domain that is used for uptake of nutrients across the outer membrane and a secreted toxic C-terminal domain. Infection experiments revealed that CpnT is required for survival and cytotoxicity of M. tuberculosis in macrophages. Furthermore, we demonstrate that the C-terminal domain of CpnT causes necrotic cell death in eukaryotic cells. Thus, CpnT has a dual function in uptake of nutrients and induction of host cell death by M. tuberculosis. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 18 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Bacterial Outer Membrane Proteins Metabolism Bacterial Toxins Exotoxins Mycobacterium Tuberculosis Amino Acid Sequence Animals Chemistry Genetics Cell Line Genes, Bacterial Glycerol HEK293 Cells Jurkat Cells Macrophages Microbiology Mice Mice, Inbred C57BL Molecular Sequence Data Mutation Mycobacterium Bovis Growth & Development Pathogenicity Phylogeny Protein Structure, Tertiary Recombinant Proteins Toxicity Sequence Homology, Amino Acid Virulence Physiology Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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