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Changes in energy metabolism of Mycobacterium tuberculosis in mouse lung and under in vitro conditions affecting aerobic respiration.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Shi, Lanbo Sohaskey, Charles D. Kana, Bavesh Davandra Dawes, Stephanie S. Mizrahi, Valerie Gennaro, Maria Laura |
| Copyright Year | 2005 |
| Abstract | Transcription profiling of genes encoding components of the respiratory chain and the ATP synthesizing apparatus of Mycobacterium tuberculosis was conducted in vivo in the infected mouse lung, and in vitro in bacterial cultures subjected to gradual oxygen depletion and to nitric oxide treatment. Transcript levels changed dramatically as infection progressed from bacterial exponential multiplication (acute infection) to cessation of bacterial growth (chronic infection) in response to host immunity. The proton-pumping type-I NADH dehydrogenase and the aa3-type cytochrome c oxidase were strongly down-regulated. Concurrently, the less energy-efficient cytochrome bd oxidase was transiently up-regulated. The nitrate transporter NarK2 was also up-regulated, indicative of increased nitrate respiration. The reduced efficiency of the respiratory chain was accompanied by decreased expression of ATP synthesis genes. Thus, adaptation of M. tuberculosis to host immunity involves three successive respiratory states leading to decreased energy production. Decreased bacterial counts in mice infected with a cydC mutant (defective in the cytochrome bd oxidase-associated transporter) at the transition to chronic infection provided initial evidence that the bd oxidase pathway is required for M. tuberculosis adaptation to host immunity. In vitro, NO treatment and hypoxia caused a switch from transcription of type I to type II NADH dehydrogenase. Moreover, cytochrome bd oxidase expression increased, but cytochrome c oxidase expression decreased slightly (nitric oxide) or not at all (hypoxia). These specific differences in respiratory metabolism during M. tuberculosis growth arrest in vitro and in vivo will guide manipulation of in vitro conditions to model bacterial adaptation to host immunity. |
| Starting Page | 3435 |
| Ending Page | 3435 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.pnas.org/content/102/43/15629.full.pdf |
| PubMed reference number | 16227431v1 |
| Volume Number | 102 |
| Issue Number | 43 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Acclimatization Adenosine Triphosphate Bacterial Count Measurement Cell Respiration Genus Mycobacterium Hypoxia Ketoglutarate Dehydrogenase Complex Mycobacterium tuberculosis NADH dehydrogenase (ubiquinone) Nitrate Nitric Oxide Oxygen Protons aa3-type cytochrome c oxidase pump (device) |
| Content Type | Text |
| Resource Type | Article |
