Co-expression of DevR and DevR(N)-Aph proteins is associated with hypoxic adaptation defect and virulence attenuation of Mycobacterium tuberculosis.

<h4>Background</h4>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 De...

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Autores principales:	Shyamasree De Majumdar, Deepak Sharma, Atul Vashist, Kohinoor Kaur, Neetu Kumra Taneja, Santosh Chauhan, Vijay K Challu, V D Ramanathan, V Balasangameshwara, Prahlad Kumar, Jaya Sivaswami Tyagi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/62e84aa0f5e84d09b69c4c1e84e9bc4f
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spelling	oai:doaj.org-article:62e84aa0f5e84d09b69c4c1e84e9bc4f2021-11-25T06:25:32ZCo-expression of DevR and DevR(N)-Aph proteins is associated with hypoxic adaptation defect and virulence attenuation of Mycobacterium tuberculosis.1932-620310.1371/journal.pone.0009448https://doaj.org/article/62e84aa0f5e84d09b69c4c1e84e9bc4f2010-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20195478/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 (DevR(NTD)) as a fusion protein with AphI (DevR(N)-Kan), and its complemented strain, Comp1, that expresses intact DevR along with DevR(N)-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.<h4>Conclusions/significance</h4>The hypoxic defect of Comp1 is associated to a defect in DevR expression level. The demonstrated repression of DevR function by DevR(N)-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.Shyamasree De MajumdarDeepak SharmaAtul VashistKohinoor KaurNeetu Kumra TanejaSantosh ChauhanVijay K ChalluV D RamanathanV BalasangameshwaraPrahlad KumarJaya Sivaswami TyagiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 2, p e9448 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shyamasree De Majumdar Deepak Sharma Atul Vashist Kohinoor Kaur Neetu Kumra Taneja Santosh Chauhan Vijay K Challu V D Ramanathan V Balasangameshwara Prahlad Kumar Jaya Sivaswami Tyagi Co-expression of DevR and DevR(N)-Aph proteins is associated with hypoxic adaptation defect and virulence attenuation of Mycobacterium tuberculosis.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 (DevR(NTD)) as a fusion protein with AphI (DevR(N)-Kan), and its complemented strain, Comp1, that expresses intact DevR along with DevR(N)-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.<h4>Conclusions/significance</h4>The hypoxic defect of Comp1 is associated to a defect in DevR expression level. The demonstrated repression of DevR function by DevR(N)-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.
format	article
author	Shyamasree De Majumdar Deepak Sharma Atul Vashist Kohinoor Kaur Neetu Kumra Taneja Santosh Chauhan Vijay K Challu V D Ramanathan V Balasangameshwara Prahlad Kumar Jaya Sivaswami Tyagi
author_facet	Shyamasree De Majumdar Deepak Sharma Atul Vashist Kohinoor Kaur Neetu Kumra Taneja Santosh Chauhan Vijay K Challu V D Ramanathan V Balasangameshwara Prahlad Kumar Jaya Sivaswami Tyagi
author_sort	Shyamasree De Majumdar
title	Co-expression of DevR and DevR(N)-Aph proteins is associated with hypoxic adaptation defect and virulence attenuation of Mycobacterium tuberculosis.
title_short	Co-expression of DevR and DevR(N)-Aph proteins is associated with hypoxic adaptation defect and virulence attenuation of Mycobacterium tuberculosis.
title_full	Co-expression of DevR and DevR(N)-Aph proteins is associated with hypoxic adaptation defect and virulence attenuation of Mycobacterium tuberculosis.
title_fullStr	Co-expression of DevR and DevR(N)-Aph proteins is associated with hypoxic adaptation defect and virulence attenuation of Mycobacterium tuberculosis.
title_full_unstemmed	Co-expression of DevR and DevR(N)-Aph proteins is associated with hypoxic adaptation defect and virulence attenuation of Mycobacterium tuberculosis.
title_sort	co-expression of devr and devr(n)-aph proteins is associated with hypoxic adaptation defect and virulence attenuation of mycobacterium tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/62e84aa0f5e84d09b69c4c1e84e9bc4f
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Co-expression of DevR and DevR(N)-Aph proteins is associated with hypoxic adaptation defect and virulence attenuation of Mycobacterium tuberculosis.

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