Cmr is a redox-responsive regulator of DosR that contributes to M. tuberculosis virulence.

Autor:	Smith LJ; Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK.; School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK., Bochkareva A; Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK., Rolfe MD; Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK., Hunt DM; Division of Mycobacterial Research, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK., Kahramanoglou C; Division of Mycobacterial Research, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK., Braun Y; Division of Mycobacterial Research, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK., Rodgers A; Division of Mycobacterial Research, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK., Blockley A; Division of Mycobacterial Research, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK., Coade S; Division of Mycobacterial Research, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK., Lougheed KEA; Division of Mycobacterial Research, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK., Hafneh NA; Department of Infection, Immunity and Inflammation, University of Leicester, University Road, Leicester LE1 9HN, UK., Glenn SM; Department of Infection, Immunity and Inflammation, University of Leicester, University Road, Leicester LE1 9HN, UK., Crack JC; Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich NR4 7TJ, UK., Le Brun NE; Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich NR4 7TJ, UK., Saldanha JW; Division of Mathematical Biology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK., Makarov V; A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, Russia., Nobeli I; Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK., Arnvig K; Institute for Structural and Molecular Biology, University College London, London WC1E 6BT, UK., Mukamolova GV; Department of Infection, Immunity and Inflammation, University of Leicester, University Road, Leicester LE1 9HN, UK., Buxton RS; Division of Mycobacterial Research, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK., Green J; Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2017 Jun 20; Vol. 45 (11), pp. 6600-6612.
DOI:	10.1093/nar/gkx406
Abstrakt:	Mycobacterium tuberculosis (MTb) is the causative agent of pulmonary tuberculosis (TB). MTb colonizes the human lung, often entering a non-replicating state before progressing to life-threatening active infections. Transcriptional reprogramming is essential for TB pathogenesis. In vitro, Cmr (a member of the CRP/FNR super-family of transcription regulators) bound at a single DNA site to act as a dual regulator of cmr transcription and an activator of the divergent rv1676 gene. Transcriptional profiling and DNA-binding assays suggested that Cmr directly represses dosR expression. The DosR regulon is thought to be involved in establishing latent tuberculosis infections in response to hypoxia and nitric oxide. Accordingly, DNA-binding by Cmr was severely impaired by nitrosation. A cmr mutant was better able to survive a nitrosative stress challenge but was attenuated in a mouse aerosol infection model. The complemented mutant exhibited a ∼2-fold increase in cmr expression, which led to increased sensitivity to nitrosative stress. This, and the inability to restore wild-type behaviour in the infection model, suggests that precise regulation of the cmr locus, which is associated with Region of Difference 150 in hypervirulent Beijing strains of Mtb, is important for TB pathogenesis. (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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