A5050930070- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Leprosy Research and Treatment
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
- Yersinia bacterium, plague, ectoparasites research
- Heat shock proteins research
- RNA and protein synthesis mechanisms
- Legume Nitrogen Fixing Symbiosis
- Nematode management and characterization studies
- Viral gastroenteritis research and epidemiology
- Parasitic Diseases Research and Treatment
- Immune responses and vaccinations
- Infectious Diseases and Tuberculosis
- Molecular Biology Techniques and Applications
- Plant nutrient uptake and metabolism
- Plant Parasitism and Resistance
- Antibiotic Resistance in Bacteria
- interferon and immune responses
- Reproductive tract infections research
- Virus-based gene therapy research
- Soybean genetics and cultivation
- Seed Germination and Physiology
- Genomics and Phylogenetic Studies
- Plant Stress Responses and Tolerance
University of Surrey
2016-2025
Westmead Institute
2010
The University of Sydney
2010
Imperial College London
1995-2007
Wellcome Trust
2005-2007
Centre National de la Recherche Scientifique
2005
Kensington College of Business
2002
St Mary's Hospital
1999-2000
Experimental Station
1993
University College London
1989-1990
Leprosy was endemic in Europe until the Middle Ages. Using DNA array capture, we have obtained genome sequences of Mycobacterium leprae from skeletons five medieval leprosy cases United Kingdom, Sweden, and Denmark. In one case, so well preserved that full de novo assembly ancient bacterial could be achieved through shotgun sequencing alone. The M. were compared with those 11 modern strains, representing diverse genotypes geographic origins. comparisons revealed remarkable genomic...
Regulation of the expression heat-shock proteins plays an important role in pathogenesis Mycobacterium tuberculosis. The response bacteria involves genome-wide changes gene expression. A combination targeted mutagenesis and whole-genome profiling was used to characterize transcription factors responsible for control genes encoding major M. Two regulons were identified. HspR acts as a transcriptional repressor members Hsp70 (DnaK) regulon, HrcA similarly regulates Hsp60 (GroE) response. These...
An impediment to the rational development of novel drugs against tuberculosis (TB) is a general paucity knowledge concerning metabolism Mycobacterium tuberculosis, particularly during infection. Constraint-based modeling provides approach investigating microbial but has not yet been applied genome-scale M. tuberculosis. GSMN-TB, metabolic model was constructed, consisting 849 unique reactions and 739 metabolites, involving 726 genes. The calibrated by growing bovis bacille Calmette Guérin in...
The pathogenesis of mycobacterial infection is associated with an ability to interfere maturation the phagosomal compartment after ingestion by macrophages. Identification components that contribute this phenomenon will allow rational design novel approaches treatment and prevention tuberculosis. Microarray-based screening a transposon library was used identify mutations influence fate Mycobacterium bovis bacille Calmette-Guérin (BCG) following uptake A screen based on bacterial survival...
The ability of the tubercle bacillus to arrest phagosome maturation is considered one major mechanism that allows its survival within host macrophages. To identify mycobacterial genes involved in this process, we developed a high throughput phenotypic cell-based assay enabling individual sub-cellular analysis over 11,000 Mycobacterium tuberculosis mutants. This very stringent makes use fluorescent staining for intracellular acidic compartments, and automated confocal microscopy...
Studying ancient DNA allows us to retrace the evolutionary history of human pathogens, such as Mycobacterium leprae, main causative agent leprosy. Leprosy is one oldest recorded and most stigmatizing diseases in history. The disease was prevalent Europe until 16th century still endemic many countries with over 200,000 new cases reported annually. Previous worldwide studies on modern European medieval M. leprae genomes revealed that they cluster into several distinct branches which two were...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA quantities, measured by reverse transcription quantitative PCR (RT-qPCR), have been proposed to stratify clinical risk or determine analytical performance targets. We investigated reproducibility and how setting diagnostic cutoffs altered the sensitivity of disease 2019 (COVID-19) testing.Quantitative SARS-CoV-2 distributions [quantification cycle (Cq) copies/mL] from more than 6000 patients 3 laboratories in United Kingdom,...
The disaccharide trehalose is the major free sugar in cytoplasm of mycobacteria; it a constituent cell wall glycolipids, and plays role mycolic acid transport during biogenesis. pleiotropic biology Mycobacterium tuberculosis its absence from mammalian cells suggests that biosynthesis may provide useful target for novel drugs. However, there are three potential pathways M. tuberculosis, aim present study was to introduce mutations into each determine whether or not they functionally...
Abstract. Interactions between parasitic angiosperms and their hosts occur at the level of seed germination, haustorial development resource transfer. Chemicals released from host function as cues for recognition, trigger germination well initiation. Transpiration is a key process regulating solute transfer to parasite, some parasitie plants have unusual stomatal characteristics. Although apoplastic, haustorium appears play role in composition. Host responses infection are reviewed, it...
Mycobacterium tuberculosis infects a third of the world's population. Primary involving active fast bacterial replication is often followed by asymptomatic latent tuberculosis, which characterised slow or non-replicating bacteria. Reactivation infection switch back to can lead post-primary transmissible tuberculosis. Mycobacterial mechanisms involved in growth switching rate provide rational targets for development new drugs against persistent mycobacterial infection. Using chemostat culture...
Abstract Mycobacterium tuberculosis infection generates pulmonary granulomas that consist of a caseous, necrotic core surrounded by an ordered arrangement macrophages, neutrophils and T cells. This inflammatory pathology is essential for disease transmission M. has evolved to stimulate granuloma development while simultaneously avoiding destruction the attracted phagocytes. The most abundant phagocyte in active neutrophil. Here we show ESAT-6 protein secreted ESX-1 type VII secretion system...
Leprosy has afflicted humankind throughout history leaving evidence in both early texts and the archaeological record. In Britain, leprosy was widespread Middle Ages until its gradual unexplained decline between 14th 16th centuries. The nature of this ancient endemic relationship to modern strains is only partly understood. Modern are currently divided into 5 phylogenetic groups, types 0 4, each with strong geographical links. Until recently, European strains, modern, were thought be...
Chronic helminth infection induces a type-2 cellular immune response. In contrast to this, mycobacterial infections commonly induce type-1 response which is considered protective. Type-2 responses and diminished mycobacteria have been previously correlated with active states such as pulmonary tuberculosis lepromatous leprosy. The present study examines the of children exposed both parasite Onchocerca volvulus infections, Mycobacterium M. leprae. Proliferation peripheral blood mononuclear...
Six major lineages of Mycobacterium tuberculosis appear preferentially transmitted amongst distinct ethnic groups. We identified a deletion affecting Rv1519 in CH, strain isolated from large outbreak Leicester U.K., that coincidentally defines the East African-Indian lineage matching group this city. In broth media, CH grew less rapidly and was acidic H 2 O -tolerant than reference sequenced strains (CDC1551 H37Rv). Nevertheless, not impaired its ability to grow human monocyte-derived...
Interactions between dendritic cells and Mycobacterium tuberculosis, the aetiological agent of tuberculosis in humans, are thought to be central anti-mycobacterial immunity. We have previously shown that M. binds human monocyte-derived mostly through C-type lectin DC-SIGN (dendritic-cell-specific intercellular molecule-3-grabbing non-integrin)/CD209, we suggested may discriminate mycobacterial species recognition mannose-capping residues on lipoglycan lipoarabinomannan bacterial envelope....
An important mechanism of Mycobacterium tuberculosis pathogenesis is the ability to control cell death pathways in infected macrophages: apoptotic bactericidal, whereas necrotic may facilitate bacterial dissemination and transmission.We examine M.tuberculosis spontaneous chemically induced macrophage using automated confocal fluorescence microscopy, image analysis, flow cytometry, plate-reader based vitality assays, strains including H37Rv, isogenic virulent avirulent Beijing lineage isolate...
Non-human primate models of Tuberculosis (TB) are one the most commonly used within experimental TB field because they closely mimic whole spectrum disease progression human TB. However, early cellular interactions pulmonary granuloma still not well understood. The use this model allows investigation into cells granulomas which cannot be undertaken in samples. Pulmonary from rhesus and cynomolgus macaques two timepoints post infection were categorised categories 1 – 6 (early to late stage...
ABSTRACT Superoxide dismutases (SODs) play an important role in protection against oxidative stress and have been shown to contribute the pathogenicity of many bacterial species. To determine function mycobacterial copper zinc-cofactored SOD (CuZnSOD), we constructed characterized Mycobacterium tuberculosis bovis BCG CuZnSOD null mutants. Both strains were more sensitive superoxides hydrogen peroxide than their respective parental strains. The survival M. unstimulated as well activated mouse...
Summary Mycobacterium tuberculosis has two members of the α‐crystallin (Acr) family molecular chaperones. Expression Acr1 is induced by exposure to hypoxia or nitric oxide and associated with bacterial persistence in a non‐replicating state. Acr2 heat shock, oxidative stress, uptake macrophages. We have shown that continues be expressed at high level during both acute chronic infection mouse model, an increased ratio acr2 : acr1 mRNA persistent phase. Deletion gene resulted decrease...
Chaperone and protease systems play essential roles in cellular homeostasis have vital functions controlling the abundance of specific proteins involved processes such as transcription, replication, metabolism virulence. Bacteria evolved accurate regulatory to control expression function chaperones potentially destructive proteases. Here, we used a combination transcriptomics, proteomics targeted mutagenesis reveal that clp gene regulator (ClgR) Mycobacterium tuberculosis activates...