Appropriate DevR (DosR)-mediated signaling determines transcriptional response, hypoxic viability and virulence of Mycobacterium tuberculosis.

PloS One
Shyamasree De MajumdarJaya Sivaswami Tyagi

Abstract

The DevR(DosR) regulon is implicated in hypoxic adaptation and virulence of Mycobacterium tuberculosis. The present study was designed to decipher the impact of perturbation in DevR-mediated signaling on these properties. M. tb complemented (Comp) strains expressing different levels of DevR were constructed in Mut1* background (expressing DevR N-terminal domain in fusion with AphI (DevR(N)-Kan) and in Mut2ΔdevR background (deletion mutant). They were compared for their hypoxia adaptation and virulence properties. Diverse phenotypes were noted; basal level expression (∼5.3±2.3 µM) when induced to levels equivalent to WT levels (∼25.8±9.3 µM) was associated with robust DevR regulon induction and hypoxic adaptation (Comp 9* and 10*), whereas low-level expression (detectable at transcript level) as in Comp 11* and Comp15 was associated with an adaptation defect. Intermediate-level expression (∼3.3±1.2 µM) partially restored hypoxic adaptation functions in Comp2, but not in Comp1* bacteria that co-expressed DevR(N)-Kan. Comp* strains in Mut1* background also exhibited diverse virulence phenotypes; high/very low-level DevR expression was associated with virulence whereas intermediate-level expression was associated with low virulence...Continue Reading

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Citations

Sep 12, 2015·The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases·Alexandre Silva ChavesHenrique Couto Teixeira
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Methods Mentioned

BETA
PCR
scrapings
Feature Extraction
Chip

Software Mentioned

Agilent Feature Extraction
Quantity One
SigA
GeneSpring GX

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