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Dibyendu Sarkar
Council of Scientific and Industrial Research
23Publications
11H-index
406Citations
Publications 24
Newest
Mycobacterium tuberculosis (Mtb) retains the unique ability to establish an asymptomatic latent infection. A fundamental question in mycobacterial physiology is to understand the mechanisms involved in hypoxic stress, a critical player in persistence. Here, we show that the virulence regulator PhoP responds to hypoxia, the dormancy signal and effectively integrates hypoxia with nitrogen metabolism. We also provide evidence to demonstrate that both under nitrogen limiting conditions and during hy...
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#1Ritesh Rajesh Sevalkar (CSIR: Council of Scientific and Industrial Research)H-Index: 3
#2Divya AroraH-Index: 4
Last.Dibyendu Sarkar (CSIR: Council of Scientific and Industrial Research)H-Index: 11
view all 7 authors...
ABSTRACT A hallmark feature of Mycobacterium tuberculosis pathogenesis lies in the ability of the pathogen to survive within macrophages under a stressful environment. Thus, coordinated regulation of stress proteins is critically important for an effective adaptive response of M. tuberculosis, the failure of which results in elevated immune recognition of the tubercle bacilli with reduced survival during chronic infections. Here, we show that virulence regulator PhoP impacts the global regulatio...
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#1S. Singh (CSIR: Council of Scientific and Industrial Research)H-Index: 3
#2Ritesh Rajesh Sevalkar (CSIR: Council of Scientific and Industrial Research)H-Index: 3
Last.Subramanian Karthikeyan (CSIR: Council of Scientific and Industrial Research)H-Index: 12
view all 4 authors...
The gene Rv1828 in Mycobacterium tuberculosis is shown to be essential for the pathogen and encodes for an uncharacterized protein. In this study, we have carried out biochemical and structural characterization of Rv1828 at the molecular level to understand its mechanism of action. The Rv1828 is annotated as helix-turn-helix (HTH)-type MerR family transcription regulator based on its N-terminal amino acid sequence similarity. The MerR family protein binds to a specific DNA sequence in the spacer...
1 CitationsSource
#1Roohi Bansal (CSIR: Council of Scientific and Industrial Research)H-Index: 4
#2Vijjamarri Anil Kumar (CSIR: Council of Scientific and Industrial Research)H-Index: 4
Last.Dibyendu Sarkar (CSIR: Council of Scientific and Industrial Research)H-Index: 11
view all 5 authors...
Summary The ability to sense acid stress and mount an appropriate adaptive response by Mycobacterium tuberculosis, which adapts a long-term residence in the macrophage phagosome, remains one of the critical features that defines mycobacterial physiology and its intracellular location. To understand the mechanistic basis of adaptation of the intracellular pathogen, we studied global regulation of M. tuberculosis gene expression in response to acid stress. Although recent studies indicate a role f...
9 CitationsSource
#1Vijjamarri Anil Kumar (CSIR: Council of Scientific and Industrial Research)H-Index: 4
#2Rajni Goyal (CSIR: Council of Scientific and Industrial Research)H-Index: 5
Last.Dibyendu Sarkar (CSIR: Council of Scientific and Industrial Research)H-Index: 11
view all 7 authors...
Abstract Attenuation of Mycobacterium bovis BCG strain is related to the loss of the RD1-encoded ESX-1 secretion system. The ESX-1 system secretes virulence factor ESAT-6 that plays a critical role in modulation of the host immune system, which is essential for establishment of a productive infection. Previous studies suggest that among the reasons for attenuation of Mycobacterium tuberculosis H37Ra is a mutation in the phoP gene that interferes with the ESX-1 secretion system and inhibits secre...
9 CitationsSource
#1Jesse S. Samuel (CSIR: Council of Scientific and Industrial Research)H-Index: 2
#2Deepak Kumar (CSIR: Council of Scientific and Industrial Research)H-Index: 8
Last.Dibyendu Sarkar (CSIR: Council of Scientific and Industrial Research)H-Index: 11
view all 7 authors...
Although unglycosylated HuEpo is fully functional, it has very short serum half-life. However, the mechanism of in vivo clearance of human Epo (HuEpo) remains largely unknown. In this study, the relative importance of protease-sensitive sites of recombinant HuEpo (rHuEpo) has been investigated by analysis of structural data coupled with in vivo half-life measurements. Our results identify α3-α4 inter-helical loop region as a target site of lysosomal protease Cathepsin L. Consistent with previous...
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#1Ramsay Macdonald (UCLA: University of California, Los Angeles)H-Index: 2
#2Dibyendu Sarkar (CSIR: Council of Scientific and Industrial Research)H-Index: 11
Last.Robert T. Clubb (UCLA: University of California, Los Angeles)H-Index: 36
view all 4 authors...
Tuberculosis caused by Mycobacterium tuberculosis is a leading cause of death world-wide. The PhoP protein is required for virulence and is part of the PhoPR two-component system that regulates gene expression. The NMR-derived solution structure of the PhoP C-terminal DNA-binding domain is reported. Residues 150 to 246 form a structured domain that contains a winged helix-turn-helix motif. We provide evidence that the transactivation loop postulated to contact RNA polymerase is partially disorde...
2 CitationsSource
#1Ranjeet Kumar Singh (CSIR: Council of Scientific and Industrial Research)H-Index: 5
#2Vijjamarri Anil Kumar (CSIR: Council of Scientific and Industrial Research)H-Index: 4
Last.Dibyendu Sarkar (CSIR: Council of Scientific and Industrial Research)H-Index: 11
view all 5 authors...
Summary The co-ordinated regulation of heat shock proteins is critically important for the stress response of M. tuberculosis, failure of which results in enhanced immune recognition of the tubercle bacilli with reduced survival during chronic infections. In this study, we show that PhoP regulates the transcription of α-crystallin 2 (acr2), expression of which increases more than any other gene of M. tuberculosis during heat-shock or following macrophage infection. We also show that regulation o...
7 CitationsSource
#1Arijit Kumar Das (CSIR: Council of Scientific and Industrial Research)H-Index: 4
#2Vijjamarri Anil Kumar (CSIR: Council of Scientific and Industrial Research)H-Index: 4
Last.Dibyendu Sarkar (CSIR: Council of Scientific and Industrial Research)H-Index: 11
view all 5 authors...
Abstract Mycobacterium tuberculosis PhoP, a master regulator involved in complex lipid biosynthesis and expression of unknown virulence determinants, is composed of an N-terminal receiver domain and a C-terminal effector domain. The two experimentally characterized PhoP orthologs, from Escherichia coli and Salmonella enterica, display vastly different regulatory capabilities. Here, we demonstrate that the twenty residues long N-terminal arm unique to M. tuberculosis PhoP plays an essential role ...
5 CitationsSource
#1Rajni GoyalH-Index: 5
#2Arijit Kumar DasH-Index: 4
Last.Dibyendu SarkarH-Index: 11
view all 6 authors...
Mycobacterium tuberculosis PhoP is essential for virulence and intracellular growth of the tubercle bacilli. Genetic evidence suggests that PhoP regulates complex lipid biosynthesis, and absence of some of these lipid molecules in a phoP mutant partly accounts for its attenuated growth in macrophages and/or mice. To investigate the mechanism of regulation, here we demonstrate the essentiality of phosphorylation of PhoP in the regulation of complex lipid biosynthesis. We show that phosphorylated ...
23 CitationsSource
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