A5025993294- Burkholderia infections and melioidosis
- Bacillus and Francisella bacterial research
- Yersinia bacterium, plague, ectoparasites research
- Bacteriophages and microbial interactions
- Chemical Looping and Thermochemical Processes
- Bacterial Genetics and Biotechnology
- Vector-borne infectious diseases
- Brucella: diagnosis, epidemiology, treatment
- Research on Leishmaniasis Studies
- Insect symbiosis and bacterial influences
- Biochemical and Molecular Research
- Clostridium difficile and Clostridium perfringens research
- Zoonotic diseases and public health
- Genomics and Phylogenetic Studies
- Enzyme Structure and Function
- Plant-based Medicinal Research
- Aquaculture Nutrition and Growth
- Fish Ecology and Management Studies
- Viral Infections and Vectors
- Religion, Society, and Development
- Viral gastroenteritis research and epidemiology
- COVID-19 epidemiological studies
- Poxvirus research and outbreaks
- Aquaculture disease management and microbiota
- Microbial infections and disease research
Defence Science and Technology Laboratory
2015-2024
University of Exeter
2016-2023
Southampton General Hospital
2023
University of Southampton
1981-2021
University of London
2003-2020
London School of Hygiene & Tropical Medicine
2003-2020
Salisbury University
2002-2013
University of Turku
2003
Imperial College London
2003
Monsanto (United States)
1981
Burkholderia pseudomallei is the causative agent of melioidosis, which a major cause morbidity and mortality in endemic regions. Currently there no human vaccine against melioidosis. In this study, LPS or capsular polysaccharide was used to immunize BALB/c mice. The different antigens induced antibody responses. Mice vaccinated with developed predominantly IgM IgG3 Contrastingly, mice IgG2b response. After immunization, were challenged by intra-peritoneal route an increased mean time death...
Stimulation of protective immune responses against intracellular pathogens is difficult to achieve using non-replicating vaccines. BALB/c mice immunized by intramuscular injection with killed Francisella tularensis (live vaccine strain) adjuvanted preformed stimulating complexes admixed CpG, were protected when systemically challenged a highly virulent strain F. (Schu S4). Serum from was used probe whole proteome microarray in order identify immunodominant antigens. Eleven out the top 12...
Glycoconjugate-based vaccines have proved to be effective at producing long-lasting protection against numerous pathogens. Here, we describe the application of bacterial protein glycan coupling technology (PGCT) generate a novel recombinant glycoconjugate vaccine. We demonstrate conjugation Francisella tularensis O-antigen Pseudomonas aeruginosa carrier exotoxin A using Campylobacter jejuni PglB oligosaccharyltransferase. The resultant F. vaccine is expressed in Escherichia coli where yields...
A Burkholderia pseudomallei mutant which was attenuated in a mouse model of melioidosis identified by signature tagged mutagenesis approach. The transposon shown to be inserted into gene within the capsular biosynthetic operon. Compared with wild-type bacteria this demonstrated 10(5)-fold increase median lethal dose and it did not react monoclonal antibody against high mol. wt polysaccharide B. pseudomallei. To determine kinetics infection, mice were dosed intraperitoneally (i.p.)...
ABSTRACT We have determined the sequence of gene cluster encoding O antigen in Francisella novicida and compared it to previously reported O-antigen tularensis subsp. . Immunization with purified lipopolysaccharide (LPS) from F. or protected against challenge holarctica , respectively. The LPS did not confer protection Allelic replacement mutants which failed produce were attenuated, but exposure these induce a protective immune response. appeared be important for intracellular survival...
ABSTRACT Burkholderia pseudomallei , the etiologic agent of melioidosis, is a CDC tier 1 select that causes severe disease in both humans and animals. Diagnosis treatment melioidosis can be challenging, absence optimal chemotherapeutic intervention, acute frequently fatal. Melioidosis an emerging infectious for which there are currently no licensed vaccines. Due to potential malicious use B. as well its impact on public health regions where endemic, significant interest developing vaccines...
Summary The two‐component regulatory system PhoPQ has been shown to regulate the expression of virulence factors in a number bacterial species. For one such factor, lipopolysaccharide (LPS), structural modifications Salmonella enterica var Typhi‐murium. In Yersinia pestis , which expresses lipo‐oligosaccharide (LOS), identified and an isogenic mutant constructed. To investigate potential LOS from Y. date not fully characterized, purified wild‐type plague phoP defective were analysed by mass...
Burkholderia pseudomallei is the causative agent of melioidosis, a disease endemic to regions Southeast Asia and Northern Australia. Both humans range other animal species are susceptible production group 3 polysaccharide capsule in B. essential for virulence. capsular (CPS) I comprises unbranched manno -heptopyranose residues encoded by 34.5-kb locus on chromosome 1. Despite importance this locus, role all genes within region unclear. We inactivated 18 these analyzed their phenotype using...
Glycosylation of proteins is known to impart novel physical properties and biological roles from both eukaryotes prokaryotes. In this study, gel-based glycoproteomics were used identify glycoproteins the potential biothreat agent Burkholderia pseudomallei closely related but nonpathogenic B. thailandensis. Top-down bottom-up mass spectrometry (MS) analyses identified that flagellin species posttranslationally modified by glycans. Analysis two strains each demonstrated with a glycan 291 Da,...
A gene cluster encoding enzymes involved in LPS O antigen biosynthesis was identified from the partial genome sequence of Francisella tularensis subsp. Schu S4. All genes within were assigned putative functions based on similarity with biosynthetic clusters other bacteria. Ten pairs overlapping primers designed to amplify by PCR nine strains F. tularensis. Although present all strains, there a size difference one products between and holarctica strains. purified S4 shown mass spectrometry...
Findings from a number of studies suggest that the PilA pilin proteins may play an important role in pathogenesis disease caused by species within genus Francisella. As such, thorough understanding structure and chemistry is warranted. Here, we definitively identified PglA protein-targeting oligosaccharyltransferase virtue its necessity for glycosylation Francisella tularensis sufficiency Escherichia coli. In addition, used mass spectrometry to examine affinity purified subsp. F. holarctica...
ABSTRACT Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei . It highly resistant to antibiotic treatment, and there currently no licensed vaccine. thailandensis close relative of but essentially avirulent in mammals. In this report, we detail the protective efficacy immunization with live B. E555, strain which has been shown express an antigenic capsule similar that Immunization E555 induced significant protection against lethal intraperitoneal challenge mouse...
Melioidosis is an emerging infectious disease caused by Burkholderia pseudomallei and associated with high morbidity mortality rates in endemic areas. Antibiotic treatment protracted not always successful; even appropriate therapy, up to 40% of individuals presenting melioidosis Thailand succumb infection. In these circumstances, effective vaccine has the potential have a dramatic impact on both scale severity disease. Currently, no vaccines are licensed for human use. A leading candidate...
The lipopolysaccharide (LPS) from eight strains of Yersinia pestis which had been cultured at 28°C appeared to be devoid an O-antigen when analysed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. LPS isolated three these 37°C also O-antigen. When the Y. strain CO92 was purified and matrix-assisted laser desorption-ionisation time-of-flight mass spectrometry, observed signals were in range predicted for molecules containing lipid A plus core oligosaccharide but lacking...
During the 2013–2016 Ebola outbreak in West Africa an expert panel was established on instructions of UK Prime Minister to identify priority pathogens for diseases that had potential cause future epidemics. A total 13 were identified, which led prioritisation spending emerging vaccine research and development from UK. This meeting report summarises process used develop pathogen list, compares it lists generated by other organisations (World Health Organisation, National Institutes Allergy...
The autotransporters are a large and diverse family of bacterial secreted outer membrane proteins, which present in many Gram-negative pathogens play role numerous environmental virulence-associated interactions. As part larger systematic study on the Burkholderia pseudomallei, causative agent severe tropical disease melioidosis, we have constructed an insertion mutant bpss1439 gene encoding unstudied predicted trimeric autotransporter adhesin. demonstrated significant reduction biofilm...
In Francisella tularensis subsp. tularensis, DsbA has been shown to be an essential virulence factor and observed migrate multiple protein spots on two-dimensional electrophoresis gels. this work, we show that the is modified with a 1,156-Da glycan moiety in O-linkage. The results of mass spectrometry studies suggest hexasaccharide, comprised N-acetylhexosamines, hexoses, unknown monosaccharide. Disruption two genes within FTT0789-FTT0800 putative polysaccharide locus, including galE...
Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei . It refractory to antibiotic treatment and there currently no licensed vaccine. In this report we detail the construction protective efficacy of polysaccharide-protein conjugate composed B. lipopolysaccharide the<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"...
There is a requirement for an efficacious vaccine to protect people against infection from Francisella tularensis, the etiological agent of tularemia. The lipopolysaccharide (LPS) F. tularensis suboptimally protective parenteral lethal challenge in mice. To develop more subunit vaccine, we have used novel biosynthetic technique protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation recombinantly conjugate O-antigen glycans immunogenic carrier Pseudomonas...
Abstract The potential for epigenetic changes in host cells following microbial infection has been widely suggested, but few examples have reported. We assessed genome-wide patterns of DNA methylation human macrophage-like U937 with Burkholderia pseudomallei , an intracellular bacterial pathogen and the causative agent melioidosis. Our analyses revealed significant cell methylation, at multiple CpG sites genome, infection. Infection induced differentially methylated probes (iDMPs) showing...