- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Pneumonia and Respiratory Infections
- Infectious Diseases and Tuberculosis
- Pneumocystis jirovecii pneumonia detection and treatment
- SARS-CoV-2 and COVID-19 Research
- Antimicrobial Resistance in Staphylococcus
- Probiotics and Fermented Foods
- Reproductive tract infections research
- Diagnosis and treatment of tuberculosis
- Genomics and Phylogenetic Studies
- Enzyme Structure and Function
- Biochemical and Molecular Research
- Salmonella and Campylobacter epidemiology
- Viral gastroenteritis research and epidemiology
- Bacterial biofilms and quorum sensing
- Advanced Proteomics Techniques and Applications
- Vibrio bacteria research studies
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Cancer therapeutics and mechanisms
- Mosquito-borne diseases and control
University of the Witwatersrand
2016-2025
National Health Laboratory Service
2016-2025
New York State College of Veterinary Medicine
2025
Cornell University
2025
National Research Foundation
2010-2024
Centre for the AIDS Programme of Research in South Africa
2017-2023
South African Medical Research Council
2018-2020
Stellenbosch University
2014
Howard Hughes Medical Institute
2014
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 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...
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...
A solvatochromic trehalose dye conjugate allows the fast and specific detection of Mycobacterium tuberculosis in sputum samples.
Recent studies suggest that baseline tuberculous sputum comprises a mixture of routinely culturable and differentially tubercle bacteria (DCTB). The latter seems to be drug tolerant dependent on resuscitation-promoting factors (Rpfs).To further explore this, we assessed from patients with tuberculosis for DCTB studied the impact exogenous culture filtrate (CF) supplementation ex vivo.Sputum samples adults HIV-1 no were used most probable number (MPN) assays supplemented CF Rpf-deficient CF,...
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...
Mycobacterium tuberculosis possesses a diversity of potential virulence factors including complex branched lipids such as the phenolic glycolipid PGL-tb. PGL-tb expression by clinical M. isolate HN878 has been associated with less efficient Th1 response and increased in mice rabbits. It suggested that W-Beijing family is only group strains an intact pks1-15 gene, required for synthesis capable producing We have found some do not produce while others may variant examined early host cytokine...
In Mycobacterium tuberculosis (Mtb), damage-induced mutagenesis is dependent on the C-family DNA polymerase, DnaE2. Included with dnaE2 in Mtb SOS regulon a putative operon comprising Rv3395c , which encodes protein of unknown function restricted primarily to actinomycetes, and Rv3394c predicted encode Y-family polymerase. These genes were previously identified as components an imuA - imuB –type mutagenic cassette widespread among bacterial genomes. Here, we confirm that (designated ′) ( )...
Peptidoglycan (PG) is a cross-linked, meshlike scaffold endowed with the strength to withstand internal pressure of bacteria. Bacteria are known heavily remodel their peptidoglycan stem peptides, yet little about physiological impact these chemical variations on cross-linking. Furthermore, there limited tools study structural variations, which can also have important implications cell wall integrity and host immunity. Cross-linking peptide chains within PG an essential process, its...
ABSTRACT Mycobacterium tuberculosis depends on aerobic respiration for growth and utilizes an aa 3 -type cytochrome c oxidase terminal electron transfer. Cytochrome maturation in bacteria requires covalent attachment of heme to apocytochrome , which occurs outside the cytoplasmic membrane. We demonstrate that M. thioredoxin-like protein Rv3673c, we named CcsX, is required insertion . Inactivation CcsX resulted loss absorbance, impaired virulence induced bd oxidase. This suggests...
Mycobacteria comprise diverse species including non-pathogenic, environmental organisms, animal disease agents and human pathogens, notably Mycobacterium tuberculosis. Considering that the mycobacterial cell wall constitutes a significant barrier to drug penetration, aim of this study was conduct comparative genomics analysis repertoire enzymes involved in peptidoglycan (PG) remodelling determine potential exploiting area bacterial metabolism for discovery new targets. We conducted an silico...
There is an urgent need for point-of-care tuberculosis (TB) diagnostic methods that are fast, inexpensive, and operationally simple. Here, we report on a bright solvatochromic dye trehalose conjugate specifically detects Mycobacterium (Mtb) in minutes. 3-Hydroxychromone (3HC) dyes, known having high fluorescence quantum yields, exhibit shifts intensity response to changes environmental polarity. We synthesized two analogs of 3HC-trehalose conjugates (3HC-2-Tre 3HC-3-Tre) determined 3HC-3-Tre...
Abstract Rapid detection of tuberculosis (TB) infection is paramount to curb further transmission. The gold standard for this remains mycobacterial culture, however emerging evidence confirms the presence differentially culturable tubercle bacteria (DCTB) in clinical specimens. These do not grow under culture conditions and require filtrate (CF), from axenic cultures Mycobacterium ( Mtb ), emerge. It has been hypothesized that molecules such as resuscitation promoting factors (Rpfs), fatty...
Mechanisms by which Mycobacterium tuberculosis (Mtb) evades pathogen recognition receptor activation during infection may offer insights for the development of improved (TB) vaccines. Whilst Mtb elicits NOD-2 through host its peptidoglycan-derived muramyl dipeptide (MDP), it masks endogenous NOD-1 ligand amidation glutamate at second position in peptidoglycan side-chains. As current BCG vaccine is derived from pathogenic mycobacteria, a similar situation prevails. To alleviate this masking...
Abstract Background Mycobacterium tuberculosis can enter into a dormant state which has resulted in one third of the world's population being infected with latent making study latency and reactivation utmost importance. M. encodes five resuscitation promoting factors (Rpfs) that bear strong similarity to lysozyme-like enzyme previously implicated bacteria vitro . We have developed an intraperitoneal infection model mice, immune modulation, models chronic similar properties mouse lungs as...
ABSTRACT The environment encountered by Mycobacterium tuberculosis during infection is genotoxic. Most bacteria tolerate DNA damage engaging specialized polymerases that catalyze translesion synthesis (TLS) across sites of damage. M. possesses two putative members the DinB class Y-family polymerases, DinB1 (Rv1537) and DinB2 (Rv3056); however, their role in tolerance, mutagenesis, survival unknown. Here, both dinB1 dinB2 are shown to be expressed vitro a growth phase-dependent manner, with...