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Status: Bibliographieeintrag

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Verfasst von:Dick, Thomas [VerfasserIn]   i
 Manjunatha, Ujjini [VerfasserIn]   i
 Kappes, Barbara [VerfasserIn]   i
 Gengenbacher, Martin [VerfasserIn]   i
Titel:Vitamin B6 biosynthesis is essential for survival and virulence of Mycobacterium tuberculosis
Verf.angabe:Thomas Dick, Ujjini Manjunatha, Barbara Kappes and Martin Gengenbacher
E-Jahr:2010
Jahr:22 September 2010
Umfang:9 S.
Fussnoten:Gesehen am 12.02.2024
Titel Quelle:Enthalten in: Molecular microbiology
Ort Quelle:Oxford [u.a.] : Wiley-Blackwell, 1987
Jahr Quelle:2010
Band/Heft Quelle:78(2010), 4, Seite 980-988
ISSN Quelle:1365-2958
Abstract:With 500000 cases of multidrug-resistant tuberculosis there is an urgent need for attractive targets to enable the discovery of novel antimycobacterials. The biosynthesis of essential cofactors is of particular interest as these pathways are absent in man and their inhibition is expected to affect the metabolism of Mycobacterium tuberculosis at multiple sites. Our data demonstrate that the pathogen synthesizes pyridoxal 5-phosphate (PLP), the bioactive form of vitamin B6, by a heteromeric PLP synthase composed of Pdx1 (Rv2606c) and Pdx2 (Rv2604c). Disruption of the pdx1 gene generated a strictly B6 auxotrophic M. tuberculosis mutant, Δpdx1. Removal of the cofactor during exponential growth or stationary phase demonstrated the essentiality of vitamin B6 biosynthesis for growth and survival of the pathogen in culture. In a tuberculosis dormancy model based on gradual oxygen depletion, de novo biosynthesis of PLP was required for regrowth of the bacillus after direct oxygen exposure. The Δpdx1 mutant showed a severe growth defect in immunocompetent mice: bacilli applied intranasally failed to persist in host tissues and were quickly cleared. We conclude that vitamin B6 biosynthesis is required for survival of M. tuberculosis in vivo and thus might represent a candidate pathway for the development of new antitubercular agents.
DOI:doi:10.1111/j.1365-2958.2010.07381.x
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.1111/j.1365-2958.2010.07381.x
 DOI: https://doi.org/10.1111/j.1365-2958.2010.07381.x
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Animal Structures
 Animals
 Bacterial Proteins
 Biosynthetic Pathways
 Disease Models, Animal
 Gene Knockout Techniques
 Gram-Positive Bacteria
 Mice
 Microbial Viability
 Mutagenesis, Insertional
 Mycobacterium tuberculosis
 Tuberculosis
 Virulence
 Vitamin B 6
K10plus-PPN:1880547546
Verknüpfungen:→ Zeitschrift

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