A5003319352- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Cancer therapeutics and mechanisms
- Biochemical and Molecular Research
- Antibiotic Resistance in Bacteria
- Pneumocystis jirovecii pneumonia detection and treatment
- DNA Repair Mechanisms
- Bacteriophages and microbial interactions
- Infectious Diseases and Tuberculosis
- Bacterial Genetics and Biotechnology
- Computational Drug Discovery Methods
- Diagnosis and treatment of tuberculosis
- Antimicrobial Resistance in Staphylococcus
- Wheat and Barley Genetics and Pathology
- RNA and protein synthesis mechanisms
- Genetic Mapping and Diversity in Plants and Animals
- Photovoltaic System Optimization Techniques
- Innovative Microfluidic and Catalytic Techniques Innovation
- HIV/AIDS drug development and treatment
- Hepatitis B Virus Studies
- Mechanisms of cancer metastasis
- Geophysical and Geoelectrical Methods
- Geophysical Methods and Applications
- Genomics and Phylogenetic Studies
- Genetics and Plant Breeding
Rutgers New Jersey Medical School
2013-2024
Rutgers, The State University of New Jersey
2013-2024
Punjab Agricultural University
2021-2024
South Dakota State University
2023-2024
AIMST University
2018
Indian Institute of Science Bangalore
2002-2017
Centro Nacional de Biotecnología
2017
Bhopal Memorial Hospital & Research Centre
2016-2017
National Institute of Allergy and Infectious Diseases
2012
National Institutes of Health
2012
The ability to store fat in the form of cytoplasmic triglyceride droplets is conserved from Saccharomyces cerevisiae humans. Although much known regarding composition and catabolism lipid droplets, molecular components necessary for biogenesis have remained obscure. Here we report characterization a gene family important droplet formation named fat-inducing transcript (FIT). FIT1 FIT2 are endoplasmic reticulum resident membrane proteins that induce accumulation cell culture when expressed...
Carbapenems such as meropenem are being investigated for their potential therapeutic utility against highly drug-resistant tuberculosis. These β-lactams target the transpeptidases that introduce interpeptide cross-links into bacterial peptidoglycan thereby controlling rigidity of envelope. Treatment Mycobacterium tuberculosis (Mtb) with β-lactamase inhibitor clavulanate together resulted in rapid, polar, cell lysis releasing cytoplasmic contents. In Mtb it has been previously demonstrated...
Active tuberculosis (TB) and latent Mycobacterium infection both require lengthy treatments to achieve durable cures. This problem has partly been attributable the existence of nonreplicating M. "persisters" that are difficult kill using conventional anti-TB treatments. Compounds target respiratory pathway have potential replicating persistent shorten TB treatment, as this is essential in metabolic states. We developed a novel pathway-specific whole-cell screen identify new respiration...
Abstract H37Rv is the most widely used Mycobacterium tuberculosis strain, and its genome globally as M. reference sequence. Here, we present Bact-Builder, a pipeline that uses consensus building to generate complete accurate bacterial sequences apply it three independently cultured sequenced aliquots of single laboratory stock. Two 4,417,942 base-pair long assemblies are 100% identical, with third differing by nucleotide. Compared existing reference, new sequence contains ~6.4 kb additional...
Abstract Groundwater is a precious resource for irrigating the crops in developing countries. This research was governed Faisalabad District of Pakistan to assess groundwater strata using GIS cum geoelectric resistivity method approach. The IX1D computer model calibrated with root mean square error (up-to 5%), obtain true soil layers’ resistivities and thicknesses each VES point based on apparent data collected by ABEM SAS 4000 Terrameter most common Schlumberger electrode array setting....
We report GSK3011724A (DG167) as a binary inhibitor of β-ketoacyl-ACP synthase (KasA) in Mycobacterium tuberculosis Genetic and biochemical studies established KasA the primary target. The X-ray crystal structure KasA-DG167 complex refined to 2.0-Å resolution revealed two interacting DG167 molecules occupying nonidentical sites substrate-binding channel KasA. binding affinities its analog, 5g, which binds only once channel, were determined, along with KasA-5g structure. strongly augmented...
New chemotherapeutic agents with novel mechanisms of action are urgently required to combat the challenge imposed by emergence drug-resistant mycobacteria. In this study, a phenotypic whole-cell screen identified 5-nitro-1,10-phenanthroline (5NP) as lead compound. 5NP-resistant isolates harbored mutations that were mapped fbiB and also resistant bicyclic nitroimidazole PA-824. Mechanistic studies confirmed 5NP is activated in an F420-dependent manner, resulting formation 1,10-phenanthroline...
Uracil DNA glycosylase (Ung (or UDG)) initiates the excision repair of an unusual base, uracil, in DNA. Ung is a highly conserved protein found all organisms. Paradoxically, loss this evolutionarily enzyme has not been seen to result severe growth phenotypes cellular life forms. In study, we chose G+C-rich genome containing bacteria (Pseudomonas aeruginosa and Mycobacterium smegmatis) as model organisms investigate biological significance ung. deficiency was created either by expression...
The triazine antitubercular JSF-2019 was of interest due to its in vitro efficacy and the nitro group shared with clinically relevant delamanid pretomanid. undergoes activation requiring F420H2 one or more nitroreductases addition Ddn. An intrabacterial drug metabolism (IBDM) platform leveraged demonstrate system kinetics, evidencing formation NO⋅ a des-nitro metabolite. Structure-activity relationship studies focused on improving solubility mouse pharmacokinetic profile culminated JSF-2513,...
Mycobacteria are an important group of human pathogens. Although the DNA repair mechanisms in mycobacteria not well understood, these vital for pathogen's persistence host macrophages. In this study, we generated a null mutation uvrB gene Mycobacterium smegmatis to allow us compare significance nucleotide excision (NER) pathway with two base pathways, initiated by uracil glycosylase (Ung) and formamidopyrimidine (Fpg or MutM), isogenic strain background. The deficient NER was most...
Oxidative damage to DNA results in the occurrence of 7,8-dihydro-8-oxoguanine (8-oxoG) genome. In eubacteria, repair such is initiated by two major base-excision enzymes, MutM and MutY. We generated a MutY-deficient strain Mycobacterium smegmatis investigate role this enzyme repair. The MutY deficiency M. did not result either noteworthy susceptibility oxidative stress or an increase mutation rate. However, rifampicin-resistant isolates showed distinct mutations...
Mycobacterium tuberculosis complex may sometimes not be detected in sputum samples of suspected multidrug-resistant (MDR-TB) patients by line probe assay (LPA) even though they are smear positive for acid-fast bacilli (AFB). This retrospective analysis was attempted to understand and document our experience with LPA detection M. diagnosis MDR-TB under programmatic conditions.One thousand two hundred ninety four suspects that were AFB, received from February November 2013, tested the presence...
Mycobacterium tuberculosis infection is responsible for a global pandemic. New drugs are needed that do not show cross-resistance with the existing front-line therapeutics. A triazine antitubercular hit led to design of related pyrimidine family. The synthesis focused series these analogs facilitated exploration their in vitro activity, cytotoxicity, and physiochemical absorption-distribution-metabolism-excretion properties. Select pyrimidines were then evaluated pharmacokinetic profiles...
Tuberculosis caused by Mycobacterium tuberculosis ( Mtb ) is a significant public health concern, exacerbated the emergence of drug-resistant TB. To combat host’s dynamic environment, encodes multiple DNA repair enzymes that play critical role in maintaining genomic integrity. possesses GC-rich genome, rendering it highly susceptible to cytosine deaminations, resulting occurrence uracils DNA. UDGs encoded ung and udgB initiate repair; hence we investigated biological impact deleting...
DNA helicases are present in all kingdoms of life and play crucial roles processes metabolism such as replication, repair, recombination, transcription. To date, however, the role during homologous recombination mycobacteria remains unknown. In this study, we show that Mycobacterium tuberculosis UvrD1 more efficiently inhibited strand exchange promoted by its cognate RecA, compared to noncognate smegmatis or Escherichia coli RecA proteins. The M. UvrD1Q276R mutant lacking helicase ATPase...
Tuberculosis, caused by Mycobacterium tuberculosis (M. tuberculosis), kills 1.6 million people annually. To bridge the gap between structure- and cell-based drug discovery strategies, we are pioneering a computer-aided paradigm that merges structure-based virtual screening with ligand-based, machine learning methods trained data. This approach successfully identified N-(3-methoxyphenyl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine (JSF-2164) as an inhibitor of purified InhA whole-cell efficacy...
Integrated computational approaches for Mycobacterium tuberculosis (Mtb) are useful to identify new molecules that could lead future (TB) drugs. Our approach uses information derived from the TBCyc pathway and genome database, Collaborative Drug Discovery TB database combined with 3D pharmacophores dual event Bayesian models of whole-cell activity lack cytotoxicity. We have prioritized a large number may act as mimics substrates metabolites in metabolome. computationally searched over...