A5102959684- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Biochemical and Molecular Research
- Diagnosis and treatment of tuberculosis
- Antibiotic Resistance in Bacteria
- Infectious Diseases and Tuberculosis
- Genomics and Phylogenetic Studies
- HIV/AIDS Impact and Responses
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Cancer therapeutics and mechanisms
- Innovative Microfluidic and Catalytic Techniques Innovation
- vaccines and immunoinformatics approaches
- Global Health and Epidemiology
- Immunodeficiency and Autoimmune Disorders
- Pneumocystis jirovecii pneumonia detection and treatment
- Biosimilars and Bioanalytical Methods
- Immune Response and Inflammation
- Immune cells in cancer
- Quality and Safety in Healthcare
- Immune responses and vaccinations
Groote Schuur Hospital
2016-2020
University of Cape Town
2016-2020
London School of Hygiene & Tropical Medicine
2014-2018
Hospital for Tropical Diseases
2016
University of London
2014-2016
Abstract Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robust (stable) markers genetic variation for phylogenetic analysis. We identify ~92k SNP across a global collection...
Abstract Mycobacterium tuberculosis drug resistance (DR) challenges effective disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive DR for 15 anti-tuberculosis drugs was compiled validated 11 them using genomic-phenotypic from 792 strains. rapid online ‘TB-Profiler’ tool developed to report...
A clear understanding of the genetic basis antibiotic resistance in Mycobacterium tuberculosis is required to accelerate development rapid drug susceptibility testing methods based on sequence. Raw genotype–phenotype correlation data were extracted as part a comprehensive systematic review develop standardised analytical approach for interpreting associated mutations rifampicin, isoniazid, ofloxacin/levofloxacin, moxifloxacin, amikacin, kanamycin, capreomycin, streptomycin,...
Improved molecular diagnostic methods for detection drug resistance in Mycobacterium tuberculosis (MTB) strains are required. Resistance to first- and second- line anti-tuberculous drugs has been associated with single nucleotide polymorphisms (SNPs) particular genes. However, these SNPs can vary between MTB lineages therefore local data is required describe different strain populations. We used whole genome sequencing (WGS) characterize 37 extensively drug-resistant (XDR) isolates from...
Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants resistance anti-tuberculosis drugs. Protein structure and interaction modelling used understand functional effects putative mutations provide insight into molecular mechanisms leading resistance.To investigate potential utility these approaches, we analysed genomes 144 Mycobacterium clinical isolates from The Special Programme...
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is the second major cause of death from an infectious disease worldwide. Recent advances in DNA sequencing are leading to ability generate whole genome information clinical isolates M. complex (MTBC). The identification informative genetic variants such as phylogenetic markers and those associated with drug resistance or virulence will help barcode Mtb context epidemiological, diagnostic studies. genomic datasets increasingly...
Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) clinical data. We developed unified analysis pipeline (UVP) ( https://github.com/CPTR-ReSeqTB/UVP ) identify variants assign lineage MTBC sequence Stringent thresholds quality control measures...
Approximately 10% of the Mycobacterium tuberculosis genome is made up two families genes that are poorly characterized due to their high GC content and highly repetitive nature. The PE PPE typified by conserved N-terminal domains incorporate proline-glutamate (PE) proline-proline-glutamate (PPE) signature motifs. They hypothesised be important virulence factors involved with host-pathogen interactions, but genetic variability complexity analysis means they typically disregarded in studies.To...
Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity BCG strains that are used around world, in part from genomic changes accumulated during vaccine production resulting differences gene expression. We compared genomes transcriptomes global collection fourteen most...
Background: Tuberculosis disease, caused by Mycobacterium tuberculosis, is a major public health problem. The emergence of M. tuberculosis strains resistant to existing treatments threatens derail control efforts. Resistance mainly conferred mutations in genes coding for drug-targets or -converting enzymes, but our knowledge these incomplete. Whole genome sequencing (WGS) an increasingly common approach rapidly characterize isolates and identify predicting antimicrobial resistance, thereby...
The emergence of resistance to anti-tuberculosis drugs is a serious and growing threat public health. Next-generation sequencing rapidly gaining traction as diagnostic tool for investigating drug in Mycobacterium tuberculosis aid treatment decisions. However, there are few little data regarding the precision such assigning profiles. We investigated two platforms (Illumina MiSeq, Ion Torrent PGM™) rapid analytic pipelines (TBProfiler, Mykrobe predictor) using well characterised reference...
Abstract DNA methylation is an epigenetic modification of the genome involved in regulating crucial cellular processes, including transcription and chromosome stability. Advances PacBio sequencing technologies can be used to robustly reveal sites. The methylome Mycobacterium tuberculosis complex poorly understood but may virulence, hypoxic survival emergence drug resistance. In most extensive study date, we characterise across 4 major lineages M . 2 africanum , leading causes disease humans....
Phylogenetic-based classification of M. tuberculosis and other bacterial genomes is a core analysis for studying evolutionary hypotheses, disease outbreaks transmission events. Whole genome sequencing providing new insights into the genomic variation underlying intra- inter-strain diversity, thereby assisting with molecular barcoding bacteria. One roadblock to strain investigation lack user-interactive solutions interrogate visualise within phylogenetic tree setting. We have developed...
Tuberculosis (TB) is a major global health problem and drug resistance compromises the efforts to control this disease. Pyrazinamide (PZA) an important used in both first second line treatment regimes. However, its complete mechanism of action remains unclear.
Rationale: There is poor understanding about protective immunity and the pathogenesis of cavitation in patients with tuberculosis.Objectives: To map pathophysiological pathways at anatomically distinct positions within human tuberculosis cavity.Methods: Biopsies were obtained from eight predetermined locations lung cavities multidrug-resistant undergoing therapeutic surgical resection (n = 14) healthy tissue control subjects without 10). RNA sequencing, immunohistochemistry, bacterial load...
We studied genomic variation in a previously selected collection of isogenic Mycobacterium tuberculosis laboratory strains subjected to one or two rounds antibiotic selection. Whole genome sequencing analysis identified eleven single, unique mutations (four synonymous, six non-synonymous, intergenic), addition drug resistance-conferring mutations, that were fixed the genomes monoresistant strains. Eight loci, present as minority variants (five three synonymous) susceptible parent strain,...
Summary Objective Patient‐level data are required to inform strategies interrupting transmission and default in patients with extensively drug‐resistant TB ( XDR ‐ ) improve models of care identify potential routes transmission. We therefore explored the experiences, lifestyle, attitudes needs uncured , who failed or interrupted therapy, living without treatment community. Methods conducted in‐depth interviews 12 community‐based from South Africa. Family members were interviewed when...
Extensively drug-resistant tuberculosis (XDR-TB) has emerged as one of the biggest threats to public health and TB control programs worldwide. XDR-TB is caused by Mycobacterium (MTB) strains resistant rifampin isoniazid, well a fluoroquinolone at least injectable aminoglycoside. Drug resistance in MTB primarily been associated with single nucleotide polymorphisms (SNPs) particular genes. However, it also shown that efflux pumps may play role MTB. Upregulation drug can decrease intracellular...
Mycobacterium tuberculosis (MTB) PE_PGRS genes belong to the PE multigene family. Although function of is unknown, it hypothesized that may be associated with antigenic variability in MTB. Whole genome sequencing analysis was performed on (n=37) extensively drug-resistant (XDR) MTB strains from Pakistan, which included Lineage 1 (East African Indian, n=2); Other lineage (n=3); 3 (Central Asian, n=24); (n=4); 4 (X3, n=1) and T group (n=3) strains. There were 107 SNPs identified 42 genes;...