CarD Is an Essential Regulator of rRNA Transcription Required for Mycobacterium tuberculosis Persistence Journal Article

Authors: Stallings, C. L.; Stephanou, N. C.; Chu, L.; Hochschild, A.; Nickels, B. E.; Glickman, M. S.
Article Title: CarD Is an Essential Regulator of rRNA Transcription Required for Mycobacterium tuberculosis Persistence
Abstract: Mycobacterium tuberculosis is arguably the world's most successful infectious agent because of its ability to control its own cell growth within the host. Bacterial growth rate is closely coupled to rRNA transcription, which in E. coli is regulated through DksA and (p)ppGpp. The mechanisms of rRNA transcriptional control in mycobacteria, which lack DksA, are undefined. Here we identify CarD as an essential mycobacterial protein that controls rRNA transcription. Loss of CarD is lethal for mycobacteria in culture and during infection of mice. CarD depletion leads to sensitivity to killing by oxidative stress, starvation, and DNA damage, accompanied by failure to reduce rRNA transcription. CarD can functionally replace DksA for stringent control of rRNA transcription, even though CarD associates with a different site on RNA polymerase. These findings highlight a distinct molecular mechanism for regulating rRNA transcription in mycobacteria that is critical for M. tuberculosis pathogenesis. © 2009 Elsevier Inc. All rights reserved.
Keywords: controlled study; unclassified drug; pathogenesis; nonhuman; animals; mice; dna damage; mus; protein depletion; animal experiment; animal model; transcription factor; transcription, genetic; bacteria (microorganisms); transcription factors; molecular mechanics; microbio; bacterial protein; mycobacterium tuberculosis; bacterial proteins; dna; transcription regulation; amino acid sequence; molecular sequence data; sequence alignment; promoter regions, genetic; nucleotide sequence; escherichia coli; growth regulation; oxidative stress; up-regulation; ribosome rna; rna, ribosomal; doxycycline; bacterium culture; corynebacterineae; tuberculosis; cell killing; humdisease; rna transcription; escherichia coli proteins; gene expression regulation, bacterial; mycobacterium smegmatis; caspase recruitment domain signaling protein; rna polymerase; transcription factor dksa; bacterial genetics; bacterial growth; starvation; microbial viability
Journal Title: Cell
Volume: 138
Issue: 1
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2009-07-10
Start Page: 146
End Page: 159
Language: English
DOI: 10.1016/j.cell.2009.04.041
PUBMED: 19596241
PROVIDER: scopus
PMCID: PMC2756155
Notes: --- - "Cited By (since 1996): 13" - "Export Date: 30 November 2010" - "CODEN: CELLB" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Linda Chu
    2 Chu