Linked Life Data

11929527

Source:http://linkedlifedata.com/resource/pubmed/id/11929527

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-4-3
pubmed:abstractText
The search for new TB drugs that rapidly and effectively sterilize the tissues and are thus able to shorten the duration of chemotherapy from the current 6 months has been hampered by a lack of understanding of the metabolism of the bacterium when in a 'persistent' or latent form. Little is known about the condition in which the bacilli survive, although laboratory models have shown that Mycobacterium tuberculosis can exist in a non-growing, drug-resistant state that may mimic persistence in vivo. Using nutrient starvation, we have established a model in which M. tuberculosis arrests growth, decreases its respiration rate and is resistant to isoniazid, rifampicin and metronidazole. We have used microarray and proteome analysis to investigate the response of M. tuberculosis to nutrient starvation. Proteome analysis of 6-week-starved cultures revealed the induction of several proteins. Microarray analysis enabled us to monitor gene expression during adaptation to nutrient starvation and confirmed the changes seen at the protein level. This has provided evidence for slowdown of the transcription apparatus, energy metabolism, lipid biosynthesis and cell division in addition to induction of the stringent response and several other genes that may play a role in maintaining long-term survival within the host. Thus, we have generated a model with which we can search for agents active against persistent M. tuberculosis and revealed a number of potential targets expressed under these conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0950-382X
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
717-31
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:11929527-Adaptation, Physiological, pubmed-meshheading:11929527-Bacterial Proteins, pubmed-meshheading:11929527-Cell Membrane, pubmed-meshheading:11929527-Electrophoresis, Gel, Two-Dimensional, pubmed-meshheading:11929527-Energy Metabolism, pubmed-meshheading:11929527-Gene Expression Profiling, pubmed-meshheading:11929527-Gene Expression Regulation, Bacterial, pubmed-meshheading:11929527-Lipids, pubmed-meshheading:11929527-Models, Biological, pubmed-meshheading:11929527-Mycobacterium tuberculosis, pubmed-meshheading:11929527-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:11929527-Oxygen, pubmed-meshheading:11929527-Protein Biosynthesis, pubmed-meshheading:11929527-RNA, Bacterial, pubmed-meshheading:11929527-Ribosomes, pubmed-meshheading:11929527-Rifampin, pubmed-meshheading:11929527-Transcription, Genetic
pubmed:year
2002
pubmed:articleTitle
Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling.
pubmed:affiliation
Respiratory Pathogens, GlaxoSmithKline, Stevenage, Herts, UK. jb75084@gsk.com
pubmed:publicationType
Journal Article, Evaluation Studies