A5072121356- Burkholderia infections and melioidosis
- Chemical Looping and Thermochemical Processes
- Vector-borne infectious diseases
- Brucella: diagnosis, epidemiology, treatment
- Viral Infections and Vectors
- Mosquito-borne diseases and control
- Bacillus and Francisella bacterial research
- Insect symbiosis and bacterial influences
- Bacterial Genetics and Biotechnology
- Genetics, Aging, and Longevity in Model Organisms
- Galectins and Cancer Biology
- Antimicrobial Peptides and Activities
- Bacteriophages and microbial interactions
- Yersinia bacterium, plague, ectoparasites research
- Biochemical and Structural Characterization
- Inhalation and Respiratory Drug Delivery
- Vibrio bacteria research studies
- Plant Pathogenic Bacteria Studies
- Porphyrin Metabolism and Disorders
- Particle Dynamics in Fluid Flows
- Viral gastroenteritis research and epidemiology
- Toxin Mechanisms and Immunotoxins
- Gut microbiota and health
- Nanoparticles: synthesis and applications
- Signaling Pathways in Disease
Defence Science and Technology Laboratory
2012-2022
University of Exeter
2013-2021
Salisbury University
2002-2013
Wellcome Sanger Institute
2004
John Radcliffe Hospital
2004
London School of Hygiene & Tropical Medicine
2004
Burkholderia pseudomallei is a recognized biothreat agent and the causative of melioidosis. This Gram-negative bacterium exists as soil saprophyte in melioidosis-endemic areas world accounts for 20% community-acquired septicaemias northeastern Thailand where half those affected die. Here we report complete genome B. pseudomallei, which composed two chromosomes 4.07 megabase pairs 3.17 pairs, showing significant functional partitioning genes between them. The large chromosome encodes many...
The Burkholderia pseudomallei K96243 genome encodes six type VI secretion systems (T6SSs), but little is known about the role of these in biology B. pseudomallei. In this study, we purified recombinant Hcp proteins from each T6SS and tested them as vaccine candidates BALB/c mouse model melioidosis. Recombinant Hcp2 protected 80% mice against a lethal challenge with K96243, while Hcp1, Hcp3, Hcp6 50% challenge. was only constitutively produced by vitro; however, it not exported to...
Melioidosis is a severe infectious disease of animals and humans caused by the Gram-negative intracellular pathogen Burkholderia pseudomallei . An Inv/Mxi-Spa-like type III protein secretion apparatus, encoded B. bsa locus, facilitates bacterial invasion epithelial cells, escape from endocytic vesicles survival. This study investigated role Bsa system in pathogenesis melioidosis murine models. bipD mutants, lacking component translocation were found to be significantly attenuated following...
Certain environmental microorganisms can cause severe human infections, even in the absence of an obvious requirement for transition through animal host replication (“accidental virulence”). To understand this process, we compared eleven isolate genomes Burkholderia pseudomallei (Bp), a tropical soil microbe and causative agent disease melioidosis. We found evidence existence several new genes Bp reference genome, identifying 282 novel supported by at least two independent lines supporting...
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...
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...
Using a transposon mutagenesis approach, we have identified mutant of Burkholderia pseudomallei that is auxotrophic for branched chain amino acids. The was shown to interrupted the ilvI gene encoding large subunit acetolactate synthase enzyme. Compared wild type, this significantly attenuated in murine model disease. Mice inoculated intraperitoneally with mutant, 35 days prior challenge, were protected against challenge dose 6,000 median lethal doses wild-type B. pseudomallei.
ABSTRACT The Burkholderia pseudomallei K96243 genome contains multiple type IV pilin-associated loci, including one encoding a putative pilus structural protein ( pilA ). A deletion mutant has reduced adherence to human epithelial cells and is less virulent in the nematode model of virulence murine melioidosis, suggesting role for pili B. virulence.
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 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...
Several candidates for a vaccine against Burkholderia pseudomallei, the causal bacterium of melioidosis, have been developed, and rational approach is now needed to select advance testing in relevant nonhuman primate models human clinical trials. Development such was topic meeting United Kingdom March 2014 attended by international candidate developers, researchers, government health officials. The focus advancement vaccines prevention natural infection, rather than protection from...
ABSTRACT In this paper we report on the susceptibilities of a range Bacillus species to human antimicrobial peptide LL-37. B. subtilis showed low level resistance killing by LL-37 (50% growth-inhibitory concentration [GI 50 ], 1 μg/ml). cereus and thuringiensis intermediate levels (GI s, 33 μg/ml 37 μg/ml, respectively). anthracis highest 40 66 The degradation culture supernatant was blocked metalloprotease inhibitors EDTA 1,10-phenanthroline, gene encoding protease responsible for not...
Melioidosis is an emerging disease of humans in Southeast Asia and tropical Australia. The bacterium causing this disease, Burkholderia pseudomallei, also considered a bioterrorism agent, as yet there no licensed vaccine for preventing B. pseudomallei infection. In study, we evaluated selected proteins (LolC, PotF, OppA) the ATP-binding cassette systems candidate antigens. Nonmembrane regions were expressed purified from Escherichia coli then candidates established mouse model When delivered...
Coxiella burnetii is a Gram-negative intracellular bacterium and the causative agent of zoonotic disease Q fever. Several rodent non-human primate models virulent phase I C. [Nine Mile (NM)I] have been developed, used to determine efficacy antibiotics vaccine candidates. However, there are several advantages using insect study host-microbe interactions, such as reduced animal use, lowered cost ease manipulation in high containment. In addition, many laboratories use avirulent II clone (NMII)...
Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease humans and animals. Gene clusters which encode capsular polysaccharide (type I O-PS) LPS II O-PS), both play roles in virulence, have previously been identified. Here, identification two further putative clusters, type III O-PS IV O-PS, reported. Mice challenged with or mutants showed increased mean times to death (7.8 11.6 days) compared those wild-type B. (3 days). To investigate possible polysaccharides...
This study aimed to provide data on the survival and site of damage Escherichia coli cells following aerosolization using two different techniques, nebulization flow focusing. Four metabolic stains were assessed for their ability detect respiratory activities membrane homeostasis in aerosolized E. cells. The degree sublethal injury increased significantly over 10-min period by Collison nebulizer, reaching up 99.9% population. In contrast, a lower proportion population was sublethally damaged...
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 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...
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"...