A5055192831- Tuberculosis Research and Epidemiology
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Mycobacterium research and diagnosis
- Oral and gingival health research
- Pneumocystis jirovecii pneumonia detection and treatment
- Antimicrobial Peptides and Activities
- Crystallization and Solubility Studies
- Biochemical and Structural Characterization
- Tryptophan and brain disorders
- Enzyme Structure and Function
- X-ray Diffraction in Crystallography
- Crystallography and molecular interactions
- Cancer Mechanisms and Therapy
- Antimicrobial Resistance in Staphylococcus
- Phenothiazines and Benzothiazines Synthesis and Activities
- PI3K/AKT/mTOR signaling in cancer
- Cytokine Signaling Pathways and Interactions
- Biochemical and Molecular Research
- Diagnosis and treatment of tuberculosis
- Pelvic floor disorders treatments
- Enzyme function and inhibition
- Urinary Bladder and Prostate Research
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Peptidase Inhibition and Analysis
Texas Biomedical Research Institute
2023-2025
Guru Jambheshwar University of Science and Technology
2024
Translational Health Science and Technology Institute
2013-2022
Symbiosis International University
2014-2020
Toxin–antitoxin (TA) systems are highly conserved in members of the Mycobacterium tuberculosis (Mtb) complex and have been proposed to play an important role physiology virulence. Nine these TA belong mazEF family, encoding intracellular MazF toxin its antitoxin, MazE. By overexpressing each nine putative homologues bovis BCG, here we show that Rv1102c (MazF3), Rv1991c (MazF6) Rv2801c (MazF9) induce bacteriostasis. The construction various single-, double- triple-mutant Mtb strains reveals...
Inorganic polyphosphate (polyP), a linear polymer of hundreds phosphate residues linked by ATP-like phosphoanhydride bonds, is found in all organisms and performs wide variety functions. This study shows that polyP accumulation occurs Mycobacterium tuberculosis upon exposure to various stress conditions. M. possesses single homolog ppk-1, we have disrupted ppk-1 the genome allelic replacement. The mutant strain exhibited negligible levels intracellular polyP, decreased expression sigF phoP,...
The need for novel vaccination strategies to control tuberculosis (TB) is underscored by the limited and variable efficacy of currently licensed vaccine, Bacille Calmette-Guerin (BCG). SigH critical Mycobacterium (Mtb) mitigate oxidative stress, in its absence Mtb unable scavenge host oxidative/nitrosative bursts. MtbΔsigH (ΔsigH) isogenic mutant induces signatures innate immunity macrophages protects rhesus macaques from a lethal challenge. To understand immune mechanisms protection via...
The expression of indoleamine 2,3-dioxygenase (IDO), a robust immunosuppressant, is significantly induced in macaque tuberculosis (TB) granulomas, where it expressed on IFN-responsive macrophages and myeloid-derived suppressor cells. IDO also highly human TB products its activity are detected patients with TB. In vivo blockade resulted the reorganization granuloma substantially greater T cells being recruited to core lesions. This correlated better immune control reduced lung M. burdens. To...
Abstract Inorganic polyphosphate (PolyP) plays an essential role in microbial stress adaptation, virulence and drug tolerance. The genome of Mycobacterium tuberculosis encodes for two kinases (PPK-1, Rv2984 PPK-2, Rv3232c) polyphosphatases ( ppx-1 , Rv0496 ppx-2 Rv1026) maintenance intracellular PolyP levels. Microbial constitute a molecular mechanism, whereby microorganisms utilize as phosphate donor synthesis ATP. In the present study we have constructed ppk-2 mutant strain M. demonstrate...
The emergence of drug-resistant strains Mycobacterium tuberculosis makes identification and validation newer drug targets a global priority. Phosphoserine phosphatase (PSP), key essential metabolic enzyme involved in conversion O-phospho-l-serine to l-serine, was characterized this study. M. genome harbors all enzymes l-serine biosynthesis including two PSP homologs: Rv0505c (SerB1) Rv3042c (SerB2). In the present study, we have biochemically SerB2 developed malachite green-based high...
The increasing incident rates of drug-resistant tuberculosis (DR-TB) is a global health concern and has been further complicated by the emergence extensive total strains. Identification new chemical entities which are compatible with first-line TB drugs, possess activity against DR-, metabolically less active bacteria required to tackle this epidemic. Here, we have performed phenotypic screening small molecule library Mycobacterium bovis BCG identified 24 scaffolds that exhibited MIC99...
Bacterial citrate lyase activity has been demonstrated in various eukaryotes, bacteria and archaea, underscoring their importance energy metabolism of the cell. While bacterial comprises three different subunits, M. tuberculosis genome lacks CitD CitF subunits complex but encodes for 2 homologs CitE Rv2498c Rv3075c. Using temperature sensitive mycobacteriophages, we were able to generate both single double citE mutant strains tuberculosis. The survival experiments revealed increased...
Chronic immune activation promotes tuberculosis (TB) reactivation in the macaque Mycobacterium (M. tuberculosis)/SIV coinfection model. Initiating combinatorial antiretroviral therapy (cART) early lowers risk of TB reactivation, but persists. Studies host-directed therapeutics (HDTs) that mitigate are, therefore, required. Indoleamine 2,3, dioxygenase (IDO), a potent immunosuppressor, is one most abundantly induced proteins NHP and human granulomas. Inhibition IDO improves responses lung,...
Stringent response pathways involving inorganic polyphosphate (PolyP) play an essential role in bacterial stress adaptation and virulence. The intracellular levels of PolyP are modulated by the activities kinase-1 (PPK1), kinase-2 (PPK2), exopolyphosphatases (PPXs). genome Mycobacterium tuberculosis encodes two functional PPXs, simultaneous deletion ppx1 ppx2 results a defect biofilm formation. We demonstrate here that these PPXs cumulatively contribute to ability M. survive...
<title>Abstract</title> The need for novel vaccination strategies to control tuberculosis (TB) is underscored by the limited and variable efficacy of currently licensed vaccine, Bacillar Calmette-Guerin (BCG). SigH critical <italic>Mycobacterium (Mtb) </italic>to mitigate oxidative stress, in its absence <italic>Mtb</italic> unable scavenge host oxidative/nitrosative bursts. <italic>MtbDsigH </italic>(<italic>DsigH</italic>) isogenic mutant induced signatures innate immune response...