PMID- 20154135
DCOM- 20100416
LR  - 20161122
IS  - 1098-5530 (Electronic)
IS  - 0021-9193 (Linking)
VI  - 192
IP  - 8
DP  - 2010 Apr
TI  - Strains of the East Asian (W/Beijing) lineage of Mycobacterium tuberculosis are
      DosS/DosT-DosR two-component regulatory system natural mutants.
PG  - 2228-38
LID - 10.1128/JB.01597-09 [doi]
AB  - As part of our ongoing efforts to uncover the phenotypic consequences of genetic 
      variability among clinical Mycobacterium tuberculosis isolates, we previously
      reported that isolates of the "East Asian" or "W/Beijing" lineage constitutively 
      overexpress the coordinately regulated transcriptional program known as the DosR 
      regulon under standard in vitro conditions. This phenotype distinguishes the
      W/Beijing lineage from all other M. tuberculosis lineages, which normally induce 
      expression of this regulon only once exposed to low oxygen or nitric oxide, both 
      of which result in inhibition of bacterial respiration and replication.
      Transcription of the DosR regulon is controlled through a two-component
      regulatory system comprising the transcription factor DosR and two possible
      cognate histidine sensor kinases, DosS and DosT. Through sequence analysis of a
      carefully selected set of isolates representing each of the major M. tuberculosis
      lineages, we describe herein a naturally occurring frameshift mutation in the
      gene encoding the DosT sensor kinase for isolates of the most recently evolved
      W/Beijing sublineages. Intriguingly, the occurrence of the frameshift mutation
      correlates precisely with the appearance of the constitutive DosR regulon
      phenotype displayed by the same "modern" W/Beijing strains. However,
      complementation studies have revealed that the mutation in dosT alone is not
      directly responsible for the constitutive DosR regulon phenotype. Our data serve 
      to highlight the evolutionary pressure that exists among distinct M. tuberculosis
      lineages to maintain tight control over DosR regulon expression.
FAU - Fallow, Ashley
AU  - Fallow A
AD  - Research Institute of the McGill University Health Centre, Montreal, Quebec,
FAU - Domenech, Pilar
AU  - Domenech P
FAU - Reed, Michael B
AU  - Reed MB
LA  - eng
GR  - 82931/Canadian Institutes of Health Research/Canada
GR  - MOP82931/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100212
PL  - United States
TA  - J Bacteriol
JT  - Journal of bacteriology
JID - 2985120R
RN  - 0 (Bacterial Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC (DevS protein, Mycobacterium tuberculosis)
RN  - EC (Protamine Kinase)
RN  - EC 2.7.3.- (DosR protein, Mycobacterium tuberculosis)
RN  - EC 2.7.3.- (DosT protein, Mycobacterium tuberculosis)
SB  - IM
MH  - Bacterial Proteins/genetics/*metabolism
MH  - Base Sequence
MH  - Frameshift Mutation/genetics/physiology
MH  - Genetic Complementation Test
MH  - Molecular Sequence Data
MH  - Mycobacterium tuberculosis/genetics/*metabolism
MH  - Protamine Kinase/genetics/*metabolism
MH  - Protein Kinases/genetics/*metabolism
MH  - Regulon/genetics/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC2849454
EDAT- 2010/02/16 06:00
MHDA- 2010/04/17 06:00
CRDT- 2010/02/16 06:00
PHST- 2010/02/16 06:00 [entrez]
PHST- 2010/02/16 06:00 [pubmed]
PHST- 2010/04/17 06:00 [medline]
AID - JB.01597-09 [pii]
AID - 10.1128/JB.01597-09 [doi]
PST - ppublish
SO  - J Bacteriol. 2010 Apr;192(8):2228-38. doi: 10.1128/JB.01597-09. Epub 2010 Feb 12.