Different roles of DosS and DosT in the hypoxic adaptation of Mycobacteria.

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.

journal_name

J Bacteriol

journal_title

Journal of bacteriology

authors

Kim MJ,Park KJ,Ko IJ,Kim YM,Oh JI

doi

10.1128/JB.00550-10

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

4868-75

issue

19

eissn

0021-9193

issn

1098-5530

pii

JB.00550-10

journal_volume

192

pub_type

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