A5086925968- Tuberculosis Research and Epidemiology
- Biochemical and Molecular Research
- Mycobacterium research and diagnosis
- Legume Nitrogen Fixing Symbiosis
- Cholesterol and Lipid Metabolism
- Microbial Metabolic Engineering and Bioproduction
- Sphingolipid Metabolism and Signaling
- Microbial Fuel Cells and Bioremediation
- Leprosy Research and Treatment
- Pharmacological Effects of Natural Compounds
- Viral gastroenteritis research and epidemiology
- Plant nutrient uptake and metabolism
- Biosensors and Analytical Detection
- Virus-based gene therapy research
- Lipid Membrane Structure and Behavior
- Nanoparticle-Based Drug Delivery
- Cassava research and cyanide
- Infectious Diseases and Tuberculosis
- Wastewater Treatment and Nitrogen Removal
- Diagnosis and treatment of tuberculosis
- ATP Synthase and ATPases Research
- Drug Transport and Resistance Mechanisms
- Bacterial Genetics and Biotechnology
- Analytical Chemistry and Chromatography
- Receptor Mechanisms and Signaling
University of Surrey
2019-2025
University of Exeter
2025
University of Oxford
2021
Catabolism of dicarboxylates at low oxygen drives N 2 fixation and promotes ammonia secretion in rhizobium-legume symbioses.
Abstract The approval of bedaquiline (BDQ) for the treatment tuberculosis has generated substantial interest in inhibiting energy metabolism as a therapeutic paradigm. However, it is not known precisely how BDQ triggers cell death Mycobacterium ( Mtb) . Using 13 C isotopomer analysis, we show that BDQ-treated Mtb redirects central carbon to induce metabolically vulnerable state susceptible genetic disruption glycolysis and gluconeogenesis. Metabolic flux profiles indicate dependent on ATP...
Metabolic flux is the final output of cellular regulation and has been extensively studied for carbon but much less known about nitrogen, which another important building block living organisms. For tuberculosis pathogen, this particularly in informing development effective drugs targeting pathogen's metabolism. Here we performed
Mycobacterium tuberculosis (Mtb) is one of the world's successful pathogens that flexibly adapts its metabolic nature during infection host, and in response to drugs. Here we used genome scale modelling coupled with differential producibility analysis (DPA) translate RNA seq datasets into metabolite signals identified drug-associated profiles. We tested four TB drugs bedaquiline (BDQ), isoniazid (INH), rifampicin (RIF) clarithromycin (CLA); conducted experiments Mtb exposed individual at...
Article4 May 2021Open Access Transparent process Metabolic fluxes for nutritional flexibility of Mycobacterium tuberculosis Khushboo Borah orcid.org/0000-0001-9030-2085 Department Microbial and Cellular Sciences, Faculty Health Medical University Surrey, Guildford, UK Search more papers by this author Tom A Mendum orcid.org/0000-0002-6331-2605 Nathaniel D Hawkins orcid.org/0000-0001-9806-312X Computational Analytical Rothamsted Research, Harpenden, Jane L Ward Michael H Beale Gerald...
is an important pathogenic bacterium commonly associated with human healthcare and community-acquired infections. In recent years,
New approaches are needed to control leprosy, but understanding of the biology causative agent Mycobacterium leprae remains rudimentary, principally because pathogen cannot be grown in axenic culture. Here, we applied 13C isotopomer analysis measure carbon metabolism M. its primary host cell, Schwann cell. We compared results this with those a related pathogen, tuberculosis, growing macrophage. Using glucose as tracer, show that whereas tuberculosis imports most amino acids directly from...
Rapid, reliable, sensitive, portable, and accurate diagnostics are required to control disease outbreaks such as COVID-19 that pose an immense burden on human health the global economy. Here we developed a loop-mediated isothermal amplification (LAMP)-based electrochemical test for detection of SARS-CoV-2 causes COVID-19. The is based oxidation-reduction reaction between pyrophosphates (generated from positive LAMP reaction) molybdate detected by cyclic voltammetry using inexpensive...
Oxysterols are critical regulators of inflammation and cholesterol metabolism in cells. They oxidation products may be differentially metabolised subcellular compartments biological fluids. New analytical methods needed to improve our understanding oxysterol trafficking the molecular interplay between cellular required maintain cholesterol/oxysterol homeostasis. Here we describe a method for isolation oxysterols using solid phase extraction quantification by liquid chromatography-mass...
Mycobacterium tuberculosis (Mtb) is one of the most formidable pathogens causing (TB), a devastating infectious disease responsible for highest human mortality and morbidity. The emergence drug resistant strains pathogen has increased burden TB tremendously new therapeutics to overcome problem resistance are urgently needed. Metabolism Mtb its interactions with host important survival virulence; this an topic research where there growing interest in developing therapies drugs that target...
Leprosy, caused by Mycobacterium leprae, has plagued humanity for thousands of years and continues to cause morbidity, disability stigmatization in two three million people today. Although effective treatment is available, the disease incidence remained approximately constant decades so new approaches, such as vaccine or drugs, are urgently needed control. Research however hampered pathogen's obligate intracellular lifestyle fact that it never been grown vitro. Consequently, despite...
Murine norovirus (MNV) infection results in a late translation shutoff that is proposed to contribute the attenuated and delayed innate immune response observed both
Metabolic fluxes are at the heart of metabolism and growth in any living system. During tuberculosis (TB) infection, pathogenic Mycobacterium (Mtb) adapts its nutritional behaviour metabolic to survive human macrophages cause infection. The infected host cells also undergo changes. However, our knowledge identification reprogrammed flux nodes remains limited. In this study, we applied systems-based 13C-metabolic analysis (MFA) measure intracellular carbon Mtb-infected THP-1 macrophages. We...
Nitrogen metabolism of Mycobacterium tuberculosis (Mtb) is crucial for the survival and virulence this pathogen inside host macrophages but little known about nitrogen sources acquired from or their route assimilation. Here we performed a systems-based analysis in intracellullar Mtb developed 15N-Flux Spectral Ratio Analysis (FSRA) to probe metabolic cross-talk between cell Mtb. We demonstrate that intracellular acquires multiple amino acids macrophage including glutamate, glutamine,...
Abstract Metabolic flux is the final output of cellular regulation and has been extensively studied for carbon but much less known about nitrogen, which another important building block living organisms. For pathogen Mycobacterium tuberculosis (Mtb), this particularly in informing development effective drugs targeting Mtb’s metabolism. Here we performed 13 C 15 N dual isotopic labelling mycobacterial steady state cultures quantified intracellular carbon-nitrogen (CN) nitrogen (N) fluxes...
Abstract Rhizobia induce nodule formation on legume roots and differentiate into bacteroids, which use plant-derived dicarboxylates as energy electron sources for reduction of atmospheric N 2 ammonia secretion to plants. Using heterogeneous genome-scale datasets, we reconstructed a model bacteroid metabolism investigate the effects varying dicarboxylate oxygen supply carbon nitrogen allocation. Modelling 13 C metabolic flux analysis in bacteroids indicate that microaerobiosis restricts...
An Azorhizobium caulinodans phaC mutant (OPS0865) unable to make poly-3-hydroxybutyrate (PHB), grows poorly on many carbon sources and cannot fix nitrogen in laboratory culture. However, when inoculated onto its host plant, Sesbania rostrata, the consistently fixed nitrogen. Upon reisolation from S. rostrata root nodules, a suppressor strain (OPS0921) was isolated that has significantly improved growth variety of also fixes The retains original mutation is synthesize PHB. Genome sequencing...
The raw datasets of oxysterol quantifications from whole cell and mitochondrial fractions THP-1 monocytes macrophages, neuronal-like SH-SH5Y cells human peripheral blood mononuclear are presented. Oxysterols were quantified using a new liquid chromatography-mass spectrometry (LC-MS) multiple reaction monitoring analysis published in the article "A quantitative LC-MS/MS method for mitochondrial-specific metabolism" Redox Biology [1]. This showed improved extraction efficiency recovery mono...