A5072243737- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Biochemical and Molecular Research
- Antibiotic Resistance in Bacteria
- Bacterial Genetics and Biotechnology
- Cancer therapeutics and mechanisms
- HIV/AIDS drug development and treatment
- DNA and Nucleic Acid Chemistry
- Diagnosis and treatment of tuberculosis
- Infectious Diseases and Tuberculosis
- Pneumocystis jirovecii pneumonia detection and treatment
- Neurological diseases and metabolism
- Bacteriophages and microbial interactions
- Porphyrin Metabolism and Disorders
- RNA and protein synthesis mechanisms
- DNA Repair Mechanisms
- Organophosphorus compounds synthesis
- HIV Research and Treatment
- Pneumonia and Respiratory Infections
- Computational Drug Discovery Methods
- Microbial Metabolism and Applications
- Cytomegalovirus and herpesvirus research
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Inhalation and Respiratory Drug Delivery
University of Cape Town
2015-2024
Wellcome Centre for Infectious Diseases Research in Africa
2013-2024
South African Medical Research Council
2015-2023
Africa University
2020-2023
National Health Laboratory Service
2010-2022
National Research Foundation
2010-2022
University of the Witwatersrand
2005-2017
Academy of Science of South Africa
2017
California Institute of Technology
2017
In-Q-Tel
2010
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetic mechanism of DNA polymerase I (Klenow)R. D. Kuchta, V. Mizrahi, P. A. Benkovic, K. Johnson, and S. J. BenkovicCite this: Biochemistry 1987, 26, 25, 8410–8417Publication Date (Print):December 1, 1987Publication History Published online1 May 2002Published inissue 1 December 1987https://pubs.acs.org/doi/10.1021/bi00399a057https://doi.org/10.1021/bi00399a057research-articleACS PublicationsRequest reuse permissionsArticle...
Identification of new drug targets is vital for the advancement discovery against Mycobacterium tuberculosis, especially given increase resistance worldwide to first- and second-line drugs. Because traditional target-based screening has largely proven unsuccessful antibiotic discovery, we have developed a scalable platform target identification in M. tuberculosis that based on whole-cell screening, coupled with whole-genome sequencing resistant mutants recombineering confirm. The method...
Long-term survival of nonreplicating Mycobacterium tuberculosis (Mtb) is ensured by the coordinated shutdown active metabolism through a broad transcriptional program called stringent response. In Mtb, this response initiated enzymatic action Rel Mtb and deletion rel produces strain (H37RvΔ ) severely compromised in maintenance long-term viability. Although aerosol inoculation mice with H37RvΔ results normal initial bacterial growth containment, ability to sustain chronic infection impaired....
ABSTRACT The stringent response utilizes hyperphosphorylated guanine [(p)ppGpp] as a signaling molecule to control bacterial gene expression involved in long-term survival under starvation conditions. In gram-negative bacteria, (p)ppGpp is produced by the activity of related RelA and SpoT proteins. Mycobacterium tuberculosis contains single homolog these proteins (Rel Mtb ) responds nutrient producing (p)ppGpp. A rel knockout strain was constructed virulent M. , H37Rv, allelic replacement....
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 contains five resuscitation-promoting factor (Rpf)-like proteins, RpfA-E, that are implicated in resuscitation of this organism from dormancy via a mechanism involving hydrolysis the peptidoglycan by Rpfs and partnering proteins. In study, rpfA-E genes were shown to be collectively dispensable for growth M. broth culture. The defect multiple mutants 'non-culturable' state induced starvation under anoxia was reversed genetic complementation or addition culture...
Summary The function of the Mycobacterium tuberculosis eukaryotic‐like protein serine/threonine kinase PknG was investigated by gene knock‐out and expression biochemical analysis. pkn G (Rv0410c), when cloned expressed in Escherichia coli , encodes a functional kinase. An vitro assay recombinant demonstrated that can autophosphorylate its domain as well 30 kDa C‐terminal portion, which contains tetratricopeptide (TPR) structural signalling motif. Western analysis revealed is located cytosol...
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...
The publication of the complete genome sequence for Mycobacterium tuberculosis H37Rv in 1998 has had a great impact on research community. Nonetheless, it is suspected that genetic differences have arisen stocks are maintained different laboratories. In order to assess consistency sequences among strains use and extent which they diverged from original strain sequenced, we carried out whole-genome sequencing six Polymorphisms at 73 sites were observed, shared lab strains, though 72 these...
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.
VCC234718, a molecule with growth inhibitory activity against Mycobacterium tuberculosis (Mtb), was identified by phenotypic screening of 15344-compound library. Sequencing VCC234718-resistant mutant Y487C substitution in the inosine monophosphate dehydrogenase, GuaB2, which subsequently validated to be primary molecular target VCC234718 Mtb. inhibits Mtb GuaB2 Ki 100 nM and is uncompetitive respect IMP NAD+. This compound binds at NAD+ site, after has bound, makes direct interactions IMP;...
possesses a large number of genes unknown or predicted function, undermining fundamental understanding pathogenicity and drug susceptibility. To address this challenge, we developed high-throughput functional genomics approach combining inducible CRISPR-interference image-based analyses morphological features sub-cellular chromosomal localizations in the related non-pathogen,
The genome sequence of Mycobacterium tuberculosis was analysed by searching for homologues genes known to be involved in the reversal or repair DNA damage Escherichia coli and related organisms. Genes necessary perform nucleotide excision (NER), base (BER), recombination, SOS mutagenesis were identified. In particular, all directly oxidative alkylative are present M. . contrast, we failed identify mismatch repair. This finding has potentially significant implications with respect stability,...
ABSTRACT Mycobacterium tuberculosis contains five genes, rpfA through rpfE , that bear significant homology to the resuscitation-promoting factor ( rpf ) gene of Micrococcus luteus whose product is required resuscitate growth dormant cultures M. and essential for this organism. Previous studies have shown deletion any one -like genes did not affect or survival in vitro. In conjunction with results whole-genome expression profiling, finding was indicative their functional redundancy. study,...
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....
ABSTRACT The effects of low extracellular pH and intracellular accumulation weak organic acids were compared with respect to fatty acid synthesis by whole cells Mycobacterium tuberculosis smegmatis . profile synthesized during exposure benzoic, nicotinic, or pyrazinoic acids, as well that observed hydrolysis the corresponding amides, was not a direct consequence modulation these compounds but reflected response inorganic stress. Analysis in crude mycobacterial cell extracts demonstrated...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRate-limiting steps in the DNA polymerase I reaction pathwayV. Mizrahi, R. N. Henrie, J. F. Marlier, K. A. Johnson, and S. BenkovicCite this: Biochemistry 1985, 24, 15, 4010–4018Publication Date (Print):July 1, 1985Publication History Published online1 May 2002Published inissue 1 July 1985https://pubs.acs.org/doi/10.1021/bi00336a031https://doi.org/10.1021/bi00336a031research-articleACS PublicationsRequest reuse permissionsArticle...