A5083101637- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Bacterial Genetics and Biotechnology
- Vitamin K Research Studies
- Biochemical and Molecular Research
- Enzyme Structure and Function
- Steroid Chemistry and Biochemistry
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Pharmacogenetics and Drug Metabolism
- RNA and protein synthesis mechanisms
- Diagnosis and treatment of tuberculosis
- Porphyrin Metabolism and Disorders
- Biochemical Acid Research Studies
- Infectious Diseases and Tuberculosis
- Vitamin C and Antioxidants Research
- CRISPR and Genetic Engineering
- Amino Acid Enzymes and Metabolism
- Ethics and Legal Issues in Pediatric Healthcare
- Cancer therapeutics and mechanisms
- Algal biology and biofuel production
- Testicular diseases and treatments
- Facial Nerve Paralysis Treatment and Research
- Microbial Community Ecology and Physiology
- Tracheal and airway disorders
University of Auckland
2014-2023
Maurice Wilkins Centre
2016-2023
University of Cape Town
2021-2022
South African Medical Research Council
2021-2022
Nottingham University Hospitals NHS Trust
2019
University of the Witwatersrand
1993-2017
Queen Elizabeth Hospital Birmingham
2016
National Health Laboratory Service
2003-2008
Trudeau Institute
2005
Transcription profiling of genes encoding components the respiratory chain and ATP synthesizing apparatus Mycobacterium tuberculosis was conducted in vivo infected mouse lung, vitro bacterial cultures subjected to gradual oxygen depletion nitric oxide treatment. Transcript levels changed dramatically as infection progressed from exponential multiplication (acute infection) cessation growth (chronic response host immunity. The proton-pumping type-I NADH dehydrogenase aa3 -type cytochrome c...
Mycobacterium tuberculosis is predicted to subsist on alternative carbon sources during persistence within the human host. Catabolism of odd- and branched-chain fatty acids, amino cholesterol generates propionyl-coenzyme A (CoA) as a terminal, three-carbon (C(3)) product. Propionate constitutes key precursor in lipid biosynthesis but toxic if accumulated, potentially implicating its metabolism M. pathogenesis. In addition well-characterized methylcitrate cycle, genome contains complete...
ABSTRACT We report here a series of five chemically diverse scaffolds that have in vitro activities on replicating and hypoxic nonreplicating bacilli by targeting the respiratory bc 1 complex Mycobacterium tuberculosis strain-dependent manner. Deletion cytochrome bd oxidase generated hypersusceptible mutant which resistance was acquired mutation qcrB . These results highlight promiscuity risk energy metabolism with new drugs.
ABSTRACT The cydAB genes from Mycobacterium smegmatis have been cloned and characterized. cydA cydB encode the two subunits of a cytochrome bd oxidase belonging to widely distributed family quinol oxidases found in prokaryotes. cydD cydC located immediately downstream putative ATP-binding cassette-type transporter. At room temperature, reduced minus oxidized difference spectra membranes purified wild-type M. displayed spectral features that are characteristic γ-proteobacterial type oxidase....
The aerobic electron transport chain in Mycobacterium smegmatis can terminate one of three possible terminal oxidase complexes. structure and function the pathway leading from menaquinol-menaquinone pool to cytochrome bc1 complex terminating aa3-type c was characterized. M. strains with mutations subunit II cyctochome were found be profoundly growth impaired, confirming importance this respiratory for mycobacterial under conditions. Disruption resulted an adaptation network that is...
We observed vitamin B(12)-mediated growth inhibition of Mycobacterium tuberculosis strain CDC1551. The B(12) sensitivity was mapped to a polymorphism in metH, encoding coenzyme B(12)-dependent methionine synthase. Vitamin B(12)-resistant suppressor mutants CDC1551 containing mutations riboswitch upstream the metE gene, which encodes B(12)-independent synthase, were isolated. Expression analysis confirmed that is transcriptional regulator M. tuberculosis.
ABSTRACT Mycobacterium tuberculosis , the causative agent of tuberculosis, possesses a class Ib ribonucleotide reductase (RNR), encoded by nrdE and nrdF2 genes, in addition to putative II RNR, nrdZ . In this study we probed relative contributions these RNRs growth persistence M. We found that targeted knockout gene could be achieved only presence complementing allele, confirming is essential under normal, vitro conditions. This observation also implied alternate small subunit nrdF1 unable...
Cholesterol can be a major carbon source for Mycobacterium tuberculosis during infection, both at an early stage in the macrophage phagosome and later within necrotic granuloma. KstR is highly conserved TetR family transcriptional repressor that regulates large set of genes responsible cholesterol catabolism. Many this regulon, including kstR, are either induced infection or essential survival M. vivo. In study, we identified two ligands KstR, which CoA thioester metabolites with four intact...
Menaquinones (MKs) are electron carriers in bacterial respiratory chains. In
This single centre study retrospectively analysed the intraoperative findings relative to source of referral for emergency scrotal explorations performed in a tertiary level paediatric surgery department.All patients who underwent exploration under care surgeons our unit between April 2008 and 2016 were identified. Clinical data obtained from contemporaneous records.Over 8-year period, 662 boys exploration: 6 (1%) internal referrals, 294 (44%) attended department (ED) directly, 271 (41%)...
Menaquinone (vitamin K2) plays a vital role in energy generation and environmental adaptation many bacteria, including the human pathogen Mycobacterium tuberculosis (Mtb). Although menaquinone levels are known to be tightly linked cellular redox/energy status of cell, regulatory mechanisms underpinning this phenomenon unclear. The first committed step biosynthesis is catalyzed by MenD, thiamine diphosphate–dependent enzyme comprising three domains. Domains I III form MenD active site, but no...
Alterations in cobalamin-dependent metabolism have marked the evolution of Mycobacterium tuberculosis into a human pathogen. However, role(s) cobalamin mycobacterial physiology remain poorly understood.
Multidrug-resistant (MDR) tuberculosis (TB) is defined by the resistance of Mycobacterium , causative organism, to first-line antibiotics rifampicin and isoniazid. Mitigating or reversing these drugs offers a means preserving extending their use in TB treatment.
Abstract DOHNAA ( 2 ) is a key catabolite in the Mycobacterium tuberculosis (Mtb) cholesterol degradation pathway. The CoA ester of has been implicated regulation gene transcription that ultimately responsible for C and D rings cholesterol. A synthetic route to reported here, by DMSO‐mediated Morita–Bayliss–Hillman‐type alkylation Hajos–Parrish dione. As date only available from microbial sources very small quantities, synthesis described will enable further studies enzymes involved Mtb...
KstR2 (Rv3557c) is one of two TetR-family transcriptional repressors cholesterol metabolism in Mycobacterium tuberculosis. The ability to degrade fully important for pathogenesis, and therefore this repressor was expressed, purified crystallized. Crystals diffracted better than 1.9 Å resolution belonged space group C2, with unit-cell parameters a = 72.3, b 90.3, c 49.7 Å, α γ 90, β 128.2°.