A5023732146- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Antibiotic Resistance in Bacteria
- Biochemical and Molecular Research
- Bacterial Genetics and Biotechnology
- Computational Drug Discovery Methods
- Cancer therapeutics and mechanisms
- RNA and protein synthesis mechanisms
- Antimicrobial Peptides and Activities
- Receptor Mechanisms and Signaling
- T-cell and B-cell Immunology
- Machine Learning in Bioinformatics
- Pharmacogenetics and Drug Metabolism
- Immune Cell Function and Interaction
- Biochemical and Structural Characterization
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Diagnosis and treatment of tuberculosis
- Clostridium difficile and Clostridium perfringens research
- Monoclonal and Polyclonal Antibodies Research
- Pneumonia and Respiratory Infections
- Transgenic Plants and Applications
- Metalloenzymes and iron-sulfur proteins
- Infectious Diseases and Tuberculosis
- Quinazolinone synthesis and applications
Washington University in St. Louis
2024
Indian Institute of Science Bangalore
2016-2023
Government of Himachal Pradesh
2015
Ω76 is a promising drug with remarkably low toxicity, which may be used in the future for treating highly resistant infections.
Moxifloxacin is central to treatment of multidrug-resistant tuberculosis. Effects moxifloxacin on the Mycobacterium tuberculosis redox state were explored identify strategies for increasing lethality and reducing prevalence extensively resistant A noninvasive biosensor a reactive oxygen species (ROS)-sensitive dye revealed that induces oxidative stress correlated with M. death. was mitigated by supplementing bacterial cultures an ROS scavenger (thiourea), iron chelator (bipyridyl), and,...
The global mechanisms and associated molecular alterations that occur in drug-resistant mycobacteria are poorly understood. To address this, we obtain genomics data then construct a genome-scale response network isoniazid-resistant Mycobacterium smegmatis apply network-mining algorithm. Through decipher an unbiased manner identify emergent vulnerabilities resistant bacilli, of which redox was prominent. Using phenotypic profiling, find bacilli exhibit collateral sensitivity to several...
The prokaryotic ubiquitous Toxin-antitoxin (TA) modules encodes for a stable toxin and an unstable antitoxin. VapBC subfamily is the most abundant Type II TA system in M. tuberculosis genome. However, exact physiological role of these systems are still unknown. Here, we have comprehensively characterized VapBC21 locus from tuberculosis. overexpression VapC21 inhibited mycobacterial growth bacteriostatic manner as expected, inhibition was abrogated upon co-expression cognate antitoxin,...
BackgroundPrecise differential diagnosis between acute viral and bacterial infections is important to enable appropriate therapy, avoid unnecessary antibiotic prescriptions optimize the use of hospital resources. A systems view host response provides opportunities for discovering sensitive robust molecular diagnostics.MethodsWe combine blood transcriptomes from six independent datasets (n = 756) with a knowledge-based human protein-protein interaction network, identifies subnetworks...
Iron-sulfur (Fe-S) cluster proteins carry out essential cellular functions in diverse organisms, including the human pathogen Mycobacterium tuberculosis ( Mtb ). The mechanisms underlying Fe-S biogenesis are poorly defined . Here, we show that SufT (Rv1466), a DUF59 domain-containing protein, is required for maturation. homodimerizes and interacts with proteins; SufS SufU. also 4Fe-4S containing aconitase SufR. Importantly, hyperactive cysteine domain mediates interaction of SufS, SufU,...
The Mycobacterium tuberculosis genome harbors nine toxin-antitoxin (TA) systems that are members of the
Abstract Cell signaling relies on second messengers to transduce signals from the sensory apparatus downstream pathway components. In bacteria, one of most important and ubiquitous messenger is small molecule cyclic diguanosine monophosphate (c‐di‐GMP). While biosynthesis, degradation, regulatory pathways controlled by c‐di‐GMP are well characterized, mechanisms through which controls these processes not entirely understood. Herein we present report a sensing sensor histidine kinase PdtaS...
Context: Tuberculosis (TB) is a major public health problem in India and principal cause of death adults, especially among the economically productive age group. accounts for one-fifth global burden TB. It estimated that about 40% Indian population infected with TB bacillus. The GenoType® MTBDRplus molecular method allows rapid diagnosis clinical samples detection most common mutations genes associated rifampicin (R) isoniazid (H) resistance. Aims: To study drug resistance mutational...
98% of T cells reside in tissues, yet nearly all human cell analyses are performed from peripheral blood. We single-cell sequenced 5.7 million ten donors' autologous blood and tonsils sought to answer key questions about receptor biology previously unanswerable by smaller-scale experiments. identified distinct clonal expansions distributions compared tonsils, with surprisingly low (1-7%) sharing. These few shared clones exhibited divergent phenotypes across bodily sites. Analysis...
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Tuberculosis (TB) treatment involves a multidrug regimen for six months, and until two it is unclear if effective. This delay can lead to the evolution of drug resistance, lung damage, disease spread, transmission. We identify blood-based 9-gene signature using computational pipeline that constructs interrogates genome-wide transcriptome-integrated protein-interaction network. The identified able determine response at week 1–2 in three independent public datasets. Signature-based R9-score...
Abstract Cell signalling relies on second messengers to transduce signals from the sensory apparatus downstream components of pathway. In bacteria, one most important and ubiquitous is small molecule cyclic diguanosine monophosphate (c-di-GMP). While biosynthesis, degradation regulatory pathways controlled by c-di-GMP are well characterized, mechanisms through which controls these processes not completely understood. Here we present first report a regulated sensor histidine kinase previously...
Abstract Mycobacterium tuberculosis (Mtb) is evolutionarily equipped to resist exogenous reactive oxygen species but shows vulnerability an increase in endogenous ROS (eROS). Since eROS unavoidable consequence of aerobic metabolism, understanding how levels are controlled essential yet remains uncharacterized. By combining the Mrx1-roGFP2 redox biosensor with transposon mutagenesis, we identified 368 genes (redoxosome) responsible for maintaining non-toxic Mtb. Integrating redoxosome a...
Abstract Moxifloxacin is central to treatment of multidrug-resistant tuberculosis. Effects moxifloxacin on Mycobacterium tuberculosis redox state were explored identify strategies for increasing lethality and reducing the prevalence extensively resistant A non-invasive biosensor an ROS-sensitive dye revealed that induces oxidative stress correlated with M. death. was mitigated by supplementing bacterial cultures ROS scavenger (thiourea), iron chelator (bipyridyl), and, after drug removal,...
Abstract Mycobacterium tuberculosis ( Mtb ) is evolutionarily equipped to resist exogenous reactive oxygen species but shows vulnerability an increase in endogenous ROS (eROS). Since eROS unavoidable consequence of aerobic metabolism, understanding how manages levels essential yet needs be characterized. By combining the Mrx1-roGFP2 redox biosensor with transposon mutagenesis, we identified 368 genes (redoxosome) responsible for maintaining homeostatic . Integrating redoxosome a global...
ABSTRACT The pharmacokinetic characterization of a drug, especially the determination its biological half-life, is an essential step during early phases drug development. An adequate half-life amongst many properties needed for selecting candidate clinical trials. Conversely, candidates possessing inadequate half-lives may be modified or eliminated from discovery pipeline altogether. Several methods exist determining drugs, namely HPLC, fluorescence assays, radioassays, radioimmunoassays,...