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Title: Cmr is a redox-responsive regulator of DosR that contributes to M. tuberculosis virulence
Authors: Smith, Laura J.
Bochkareva, Aleksandra
Rolfe, Matthew D.
Hunt, Debbie M.
Kahramanoglou, Christina
Braun, Yvonne
Rodgers, Angela
Blockley, Alix
Coade, Stephen
Lougheed, Kathryn E. A.
Hafneh, Nor Azian
Glenn, Sarah M.
Crack, Jason C.
Le Brun, Nick E.
Saldanha, José W.
Makarov, Vadim
Nobeli, Irene
Arnvig, Kristine
Mukamolova, Galina V
Buxton, Roger S.
Green, Jeffrey
First Published: 20-Jun-2017
Publisher: Oxford University Press (OUP)
Citation: Nucleic Acids Research, 2017, 45 (11), pp. 6600-6612
Abstract: 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. Acmr 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.
DOI Link: 10.1093/nar/gkx406
ISSN: 0305-1048
eISSN: 1362-4962
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: Supplementary Data are available at NAR Online.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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