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Carbon flux rerouting during Mycobacterium tuberculosis growth arrest.
Shi, Lanbo; Sohaskey, Charles D; Pheiffer, Carmen; Pfeiffer, Carmen; Datta, Pratik; Parks, Michael; McFadden, Johnjoe; North, Robert J; Gennaro, Maria L.
Afiliación
  • Shi L; Public Health Research Institute, New Jersey Medical School, Newark, NJ 07103, USA.
Mol Microbiol ; 78(5): 1199-215, 2010 Dec.
Article en En | MEDLINE | ID: mdl-21091505
ABSTRACT
A hallmark of the Mycobacterium tuberculosis life cycle is the pathogen's ability to switch between replicative and non-replicative states in response to host immunity. Transcriptional profiling by qPCR of ∼ 50 M. tuberculosis genes involved in central and lipid metabolism revealed a re-routing of carbon flow associated with bacterial growth arrest during mouse lung infection. Carbon rerouting was marked by a switch from metabolic pathways generating energy and biosynthetic precursors in growing bacilli to pathways for storage compound synthesis during growth arrest. Results of flux balance analysis using an in silico metabolic network were consistent with the transcript abundance data obtained in vivo. Similar transcriptional changes were seen in vitro when M. tuberculosis cultures were treated with bacteriostatic stressors under different nutritional conditions. Thus, altered expression of key metabolic genes reflects growth rate changes rather than changes in substrate availability. A model describing carbon flux rerouting was formulated that (i) provides a coherent interpretation of the adaptation of M. tuberculosis metabolism to immunity-induced stress and (ii) identifies features common to mycobacterial dormancy and stress responses of other organisms.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Carbono / Mycobacterium tuberculosis Límite: Animals / Humans Idioma: En Revista: Mol Microbiol Asunto de la revista: BIOLOGIA MOLECULAR / MICROBIOLOGIA Año: 2010 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Carbono / Mycobacterium tuberculosis Límite: Animals / Humans Idioma: En Revista: Mol Microbiol Asunto de la revista: BIOLOGIA MOLECULAR / MICROBIOLOGIA Año: 2010 Tipo del documento: Article País de afiliación: Estados Unidos