| pubmed-article:19797356 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19797356 | lifeskim:mentions | umls-concept:C0024501 | lld:lifeskim |
| pubmed-article:19797356 | lifeskim:mentions | umls-concept:C0026926 | lld:lifeskim |
| pubmed-article:19797356 | lifeskim:mentions | umls-concept:C0035203 | lld:lifeskim |
| pubmed-article:19797356 | lifeskim:mentions | umls-concept:C0001480 | lld:lifeskim |
| pubmed-article:19797356 | lifeskim:mentions | umls-concept:C0022159 | lld:lifeskim |
| pubmed-article:19797356 | lifeskim:mentions | umls-concept:C0019868 | lld:lifeskim |
| pubmed-article:19797356 | lifeskim:mentions | umls-concept:C1546857 | lld:lifeskim |
| pubmed-article:19797356 | pubmed:issue | Pt 1 | lld:pubmed |
| pubmed-article:19797356 | pubmed:dateCreated | 2009-12-23 | lld:pubmed |
| pubmed-article:19797356 | pubmed:abstractText | The ability of Mycobacterium tuberculosis to persist in its human host despite extensive chemotherapy is thought to be based on subpopulations of non-replicating phenotypically drug-resistant bacilli. To study the non-growing pathogen, culture models that generate quiescent organisms by either oxygen depletion in nutrient-rich medium (Wayne model) or nutrient deprivation in oxygen-rich medium (Loebel model) have been developed. In contrast to the energy metabolism of Wayne bacilli, little is known about Loebel bacilli. Here we analysed M. tuberculosis under nutrient-starvation conditions. Upon shifting to the non-replicating state the pathogen maintained a fivefold reduced but constant intracellular ATP level. Chemical probing of the F(0)F(1) ATP synthase demonstrated the importance of this enzyme for ATP homeostasis and viability of the nutrient-starved organism. Surprisingly, the specific ATP synthase inhibitor TMC207 did not affect viability and only moderately reduced the intracellular ATP level of nutrient-starved organisms. Depletion of oxygen killed Loebel bacilli, whereas death was prevented by nitrate, suggesting that respiration and an exogenous electron acceptor are required for maintaining viability. Nutrient-starved bacilli lacking the glyoxylate shunt enzyme isocitrate lyase failed to reduce their intracellular ATP level and died, thus establishing a link between ATP control and intermediary metabolism. We conclude that reduction of the ATP level might be an important step in the adaptation of M. tuberculosis to non-growing survival. | lld:pubmed |
| pubmed-article:19797356 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19797356 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19797356 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19797356 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19797356 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19797356 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19797356 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19797356 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19797356 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19797356 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:19797356 | pubmed:issn | 1465-2080 | lld:pubmed |
| pubmed-article:19797356 | pubmed:author | pubmed-author:PetheKevinK | lld:pubmed |
| pubmed-article:19797356 | pubmed:author | pubmed-author:DickThomasT | lld:pubmed |
| pubmed-article:19797356 | pubmed:author | pubmed-author:GengenbacherM... | lld:pubmed |
| pubmed-article:19797356 | pubmed:author | pubmed-author:RaoSrinivasa... | lld:pubmed |
| pubmed-article:19797356 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19797356 | pubmed:volume | 156 | lld:pubmed |
| pubmed-article:19797356 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19797356 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19797356 | pubmed:pagination | 81-7 | lld:pubmed |
| pubmed-article:19797356 | pubmed:meshHeading | pubmed-meshheading:19797356... | lld:pubmed |
| pubmed-article:19797356 | pubmed:meshHeading | pubmed-meshheading:19797356... | lld:pubmed |
| pubmed-article:19797356 | pubmed:meshHeading | pubmed-meshheading:19797356... | lld:pubmed |
| pubmed-article:19797356 | pubmed:meshHeading | pubmed-meshheading:19797356... | lld:pubmed |
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| pubmed-article:19797356 | pubmed:meshHeading | pubmed-meshheading:19797356... | lld:pubmed |
| pubmed-article:19797356 | pubmed:meshHeading | pubmed-meshheading:19797356... | lld:pubmed |
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| pubmed-article:19797356 | pubmed:meshHeading | pubmed-meshheading:19797356... | lld:pubmed |
| pubmed-article:19797356 | pubmed:meshHeading | pubmed-meshheading:19797356... | lld:pubmed |
| pubmed-article:19797356 | pubmed:meshHeading | pubmed-meshheading:19797356... | lld:pubmed |
| pubmed-article:19797356 | pubmed:meshHeading | pubmed-meshheading:19797356... | lld:pubmed |
| pubmed-article:19797356 | pubmed:meshHeading | pubmed-meshheading:19797356... | lld:pubmed |
| pubmed-article:19797356 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:19797356 | pubmed:articleTitle | Nutrient-starved, non-replicating Mycobacterium tuberculosis requires respiration, ATP synthase and isocitrate lyase for maintenance of ATP homeostasis and viability. | lld:pubmed |
| pubmed-article:19797356 | pubmed:affiliation | Novartis Institute for Tropical Diseases Pte Ltd, 10 Biopolis Road, #05-01 Chromos, 138670, Singapore. martin.gengenbacher@novartis.com | lld:pubmed |
| pubmed-article:19797356 | pubmed:publicationType | Journal Article | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:19797356 | lld:pubmed |
