Co-Expression of DevR and DevRN-Aph Proteins Is Associated with Hypoxic Adaptation Defect and Virulence Attenuation of Mycobacterium tuberculosis

Majumdar, S De and Sharma, D and Vashis, Atul and Kaur, K and Taneja, N K and Chauhan, S and Challu, V K and Ramanathan, V D and Balasangameshwara, V and Kumar, P and Tyagi, J S (2010) Co-Expression of DevR and DevRN-Aph Proteins Is Associated with Hypoxic Adaptation Defect and Virulence Attenuation of Mycobacterium tuberculosis. Plos One, 5 (2). e9448. ISSN Electronic: 1932-6203

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Abstract

Background: The DevR response regulator is implicated in both hypoxic adaptation and virulence of Mycobacterium tuberculosis (M. tb). DevR regulon genes are powerfully induced in vivo implicating them in bacterial adaptation to host control strategies. A better understanding of DevR function will illumine the way for new strategies to control and treat tuberculosis. Methodology/Principal Findings: Towards this objective, we used a combination of genetic, microbiological, biochemical, cell biological tools and a guinea pig virulence assay to compare the hypoxic adaptation and virulence properties of two novel M. tb strains, namely, a devR disruption mutant, Mut1, that expresses C-terminal truncated N-terminal domain of DevR (DevRNTD) as a fusion protein with AphI (DevRN-Kan), and its complemented strain, Comp1, that expresses intact DevR along with DevRN-Kan. Comp1 bacteria exhibit a defect in DevR-mediated phosphosignalling, hypoxic induction of HspX and also hypoxic survival. In addition, we find that Comp1 is attenuated in virulence in guinea pigs and shows decreased infectivity of THP-1 cells. While Mut1 bacilli are also defective in hypoxic adaptation and early growth in spleen, they exhibit an overall virulence comparable to that of wild-type bacteria. Conclusions/Significance: The hypoxic defect of Comp1 is associated to a defect in DevR expression level. The demonstrated repression of DevR function by DevRN-Kan suggests that such a knockdown approach could be useful for evaluating the activity of DevRS and other two-component signaling pathways. Further investigation is necessary to elucidate the mechanism underlying Comp1 attenuation.

Affiliation:	National Institute for Research in Tuberculosis
Item Type:	Article
Uncontrolled Keywords:	DevR, DevRN-Aph, Proteins, Hypoxic Adaptation Defect, Virulence Attenuation, Mycobacterium tuberculosis
Subjects:	Tuberculosis > Laboratory Research > Pathological
Divisions:	Basic Science Research > Clinical Pathology
Depositing User:	Dr. Rathinasabapati R
Date Deposited:	17 Mar 2022 11:34
Last Modified:	17 Mar 2022 11:34
URI:	http://eprints.nirt.res.in/id/eprint/1029

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