Different Roles of DosS and DosT in the Hypoxic Adaptation of Mycobacteria
Open Access
- 1 October 2010
- journal article
- research article
- Published by American Society for Microbiology in Journal of Bacteriology
- Vol. 192 (19), 4868-4875
- https://doi.org/10.1128/jb.00550-10
Abstract
The DosS (DevS) and DosT histidine kinases form a two-component system together with the DosR (DevR) response regulator in Mycobacterium tuberculosis. DosS and DosT, which have high sequence similarity to each other over the length of their amino acid sequences, contain two GAF domains (GAF-A and GAF-B) in their N-terminal sensory domains. Complementation tests in conjunction with phylogenetic analysis showed that DevS of Mycobacterium smegmatis is more closely related to DosT than DosS. We also demonstrated in vivo that DosS and DosT of M. tuberculosis play a differential role in hypoxic adaptation. DosT responds to a decrease in oxygen tension more sensitively and strongly than DosS, which might be attributable to their different autooxidation rates. The different responsiveness of DosS and DosT to hypoxia is due to the difference in their GAF-A domains accommodating the hemes. Multiple alignment analysis of the GAF-A domains of mycobacterial DosS (DosT) homologs and subsequent site-directed mutagenesis revealed that just one substitution of E87, D90, H97, L118, or T169 of DosS with the corresponding residue of DosT is sufficient to convert DosS to DosT with regard to the responsiveness to changes in oxygen tension.Keywords
This publication has 40 references indexed in Scilit:
- The DosR regulon of M. tuberculosis and antibacterial toleranceTuberculosis, 2009
- DevS Oxy Complex Stability Identifies This Heme Protein as a Gas Sensor in Mycobacterium tuberculosis DormancyBiochemistry, 2009
- Structural Insight into the Heme-based Redox Sensing by DosS from Mycobacterium tuberculosisPublished by Elsevier BV ,2009
- Role of the dosR - dosS Two-Component Regulatory System in Mycobacterium tuberculosis Virulence in Three Animal ModelsInfection and Immunity, 2009
- Structural analysis of fish versus mammalian hemoglobins: Effect of the heme pocket environment on autooxidation and hemin lossProteins-Structure Function and Bioinformatics, 2009
- 2.3 Å X-ray Structure of the Heme-Bound GAF Domain of Sensory Histidine Kinase DosT of Mycobacterium tuberculosisBiochemistry, 2008
- DosT and DevS are oxygen‐switched kinases in Mycobacterium tuberculosisProtein Science, 2007
- Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensorProceedings of the National Academy of Sciences of the United States of America, 2007
- DevS, a Heme-Containing Two-Component Oxygen Sensor of Mycobacterium tuberculosisBiochemistry, 2007
- Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mpl8 and pUC19 vectorsGene, 1985