A5079123140- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Antimicrobial Resistance in Staphylococcus
- Bacterial Identification and Susceptibility Testing
- SARS-CoV-2 and COVID-19 Research
- Antibiotic Resistance in Bacteria
- Biochemical and Molecular Research
- Genomics and Phylogenetic Studies
- Bacterial biofilms and quorum sensing
- COVID-19 Clinical Research Studies
- Microbial Community Ecology and Physiology
- Diagnosis and treatment of tuberculosis
- Clostridium difficile and Clostridium perfringens research
- Bacteriophages and microbial interactions
- SARS-CoV-2 detection and testing
- Salmonella and Campylobacter epidemiology
- Reproductive tract infections research
- Microbial Metabolism and Applications
- COVID-19 epidemiological studies
- RNA and protein synthesis mechanisms
- Escherichia coli research studies
- Infectious Diseases and Tuberculosis
- Agriculture, Soil, Plant Science
- Antibiotic Use and Resistance
- Syphilis Diagnosis and Treatment
London School of Hygiene & Tropical Medicine
2016-2025
Wellcome Sanger Institute
2012-2025
University of London
2014-2022
University of Cambridge
2016-2021
University College London
2021
University of Geneva
2019
University of Oxford
2019
Imperial College Healthcare NHS Trust
2019
World Health Organization
2019
Hospital for Tropical Diseases
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...
The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. is suspected that associated with more severe disease than previously dominant alpha (B.1.1.7) variant. We aimed characterise severity of compared by determining relative risk hospital attendance outcomes.
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...
To improve understanding of the factors influencing tuberculosis transmission and role pathogen variation, we sequenced all available specimens from patients diagnosed over 15 years in a whole district Malawi. Mycobacterium lineages were assigned networks constructed, allowing ≤10 single nucleotide polymorphisms (SNPs) difference. We defined disease as due to recent infection if network-determined source was within 5 years, assessed transmissibility forward transmissions resulting disease....
Molecular diagnostics are considered the most promising route to achieving rapid, universal drug susceptibility testing for
The increasing prevalence of E. coli bloodstream infections is a serious public health problem. We used genomic epidemiology in One Health study conducted the East England to examine putative sources associated with human disease. from 1,517 patients were compared 431 isolates livestock farms and meat. Livestock-associated genetically distinct populations based on core genome accessory analyses. Identical antimicrobial resistance genes found isolates, but there was limited overlap mobile...
Background. Recurrent tuberculosis is a major health burden and may be due to relapse with the original strain or reinfection new strain.
Longitudinal genomic and epidemiological surveillance of methicillin-resistant Staphylococcus aureus in the UK reveals extensive transmission hospitals community.
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...
Whole-genome sequencing (WGS) can be used in genomic epidemiology investigations to confirm or refute outbreaks of bacterial pathogens, and support targeted efficient infection control interventions. We aimed define a genetic relatedness cutoff, quantified as number single-nucleotide polymorphisms (SNP), for meticillin-resistant Staphylococcus aureus (MRSA), above which recent (ie, within 6 months) patient-to-patient transmission could ruled out.We did retrospective epidemiological analysis...
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...
Vancomycin-resistant Enterococcus faecium (VREfm) is a leading cause of nosocomial infection. Here, we describe the utility whole-genome sequencing in defining VREfm transmission.
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...
BackgroundDNA sequencing could become an alternative to in vitro antibiotic susceptibility testing (AST) methods for determining resistance by detecting genetic determinants associated with decreased susceptibility. Here, we aimed assess and improve the accuracy of determination from Enterococcus faecium genomes diagnosis surveillance purposes.MethodsIn this retrospective diagnostic study, first conducted a literature search PubMed on Jan 14, 2021, compile catalogue genes mutations...
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...
Abstract Summary: Spoligotyping is a well-established genotyping technique based on the presence of unique DNA sequences in Mycobacterium tuberculosis (Mtb), causal agent disease (TB). Although advances sequencing technologies are leading to whole-genome bacterial characterization, tens thousands isolates have been spoligotyped, giving global view Mtb strain diversity. To bridge gap, we developed SpolPred, software predict spoligotype from raw sequence reads. Our approach compared with...
Background Understanding the emergence and spread of multidrug-resistant tuberculosis (MDR-TB) is crucial for its control. MDR-TB in previously treated patients generally attributed to selection drug resistant mutants during inadequate therapy rather than transmission a strain. Traditional genotyping methods are not sufficient distinguish strains populations with high burden it has been difficult assess degree these settings. We have used whole genome analysis investigate M. isolated from...
Abstract Background Antibiotics remain the cornerstone of modern medicine. Yet there exists an inherent dilemma in their use: we are able to prevent harm by administering antibiotic treatment as necessary both humans and animals, but must be mindful limiting spread resistance safeguarding efficacy antibiotics for current future generations. Policies that strike right balance informed a transparent rationale relies on robust evidence base. Main text One way generate base needed inform...
Antibiotic resistance hinders the treatment of bacterial infection. To guide effective therapy, clinical microbiology laboratories routinely perform susceptibility testing to determine antibiotic sensitivity an infecting pathogen. This approach relies on assumption that it can reliably distinguish bacteria capable expressing in patients, idea challenged by present study. We report important human pathogen Staphylococcus aureus frequently carries genes have become inactivated (“silenced”)...
Multidrug- (MDR) and extensively drug resistant (XDR) tuberculosis (TB) presents a challenge to disease control elimination goals. In Lisbon, Portugal, specific successful XDR-TB strains have been found in circulation for almost two decades. the present study we genotyped sequenced genomes of 56 Mycobacterium isolates recovered mostly from Lisbon. The genotyping data revealed three major clusters associated with MDR-TB, which are XDR-TB. Whilst genomic contributed elucidate phylogenetic...