Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling.
Mol Microbiol
; 43(3): 717-31, 2002 Feb.
Article
en En
| MEDLINE
| ID: mdl-11929527
ABSTRACT
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_neglected_diseases
/
3_tuberculosis
Asunto principal:
Proteínas Bacterianas
/
Mycobacterium tuberculosis
Tipo de estudio:
Evaluation_studies
Idioma:
En
Revista:
Mol Microbiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
MICROBIOLOGIA
Año:
2002
Tipo del documento:
Article
País de afiliación:
Reino Unido