A5070238848- Pneumonia and Respiratory Infections
- Escherichia coli research studies
- Streptococcal Infections and Treatments
- Salmonella and Campylobacter epidemiology
- Bacteriophages and microbial interactions
- Viral gastroenteritis research and epidemiology
- Glycosylation and Glycoproteins Research
- Bacterial Infections and Vaccines
- Microbial infections and disease research
- Pneumocystis jirovecii pneumonia detection and treatment
- Respiratory viral infections research
- Veterinary medicine and infectious diseases
- Leaf Properties and Growth Measurement
- Plant Pathogenic Bacteria Studies
- Aquaculture disease management and microbiota
- Biochemical and Structural Characterization
- Antimicrobial Resistance in Staphylococcus
- Helicobacter pylori-related gastroenterology studies
- Insect symbiosis and bacterial influences
- Carbohydrate Chemistry and Synthesis
- Plant Diversity and Evolution
- Peptidase Inhibition and Analysis
- Fern and Epiphyte Biology
- African Botany and Ecology Studies
- Invertebrate Immune Response Mechanisms
University of London
2012-2024
London School of Hygiene & Tropical Medicine
2012-2024
Google (United States)
2016
Terra
2016
University of Leicester
2008-2015
Imperial College London
2015
Abstract Streptococcus suis causes disease in pigs worldwide and is increasingly implicated zoonotic East South-East Asia. To understand the genetic basis of S. , we study genomes 375 isolates with detailed clinical phenotypes from humans United Kingdom Vietnam. Here, show that associated contain substantially fewer genes than non-clinical isolates, but are more likely to encode virulence factors. Human limited a single-virulent population, originating 1920, s when pig production was...
Actinobacillus pleuropneumoniae is responsible for swine pleuropneumonia, a respiratory disease that causes significant global economic loss. Its virulence depends on many factors, such as capsular polysaccharides, RTX toxins and iron-acquisition systems. Analysis of may require easy-to-use models approximate mammalian infection avoid ethical issues. Here, we investigate the potential use wax moth Galleria mellonella an informative model A. infection. Genotypically distinct clinical isolates...
ABSTRACT Knowledge of the in vivo physiology and metabolism Streptococcus pneumoniae is limited, even though pneumococci rely on efficient acquisition host nutrients for growth survival. Because nutrient-limited, hypoxic tissues favor mixed-acid fermentation, we studied role pneumococcal pyruvate formate lyase (PFL), a key enzyme which activated posttranslationally by PFL-activating (PFL-AE). Mutations were introduced to two putative pfl genes, SPD0235 SPD0420, A SPD0229 SPD1774. End-product...
Currently, Streptococcus pneumoniae is responsible for over 14 million cases of pneumonia worldwide annually, and 1 deaths, the majority them children. The major determinant pathogenesis a polysaccharide capsule that variable used to distinguish strains based on their serotype. forms basis pneumococcal vaccine (PPV23) contains purified capsular from 23 serotypes, conjugate (PCV13), containing 13 common serotypes conjugated CRM197 (mutant diphtheria toxin). Purified S. required production,...
The pneumococcus obtains its energy from the metabolism of host glycosides. Therefore, efficient degradation glycoproteins is integral to pneumococcal virulence. In search novel glycosidases, we characterized Streptococcus pneumoniae strain D39 protein encoded by SPD_0065 and found that this gene encodes a beta-galactosidase. recombinant released galactose desialylated fetuin, which was used here as model in vivo. A mutant with mutation showed diminished beta-galactosidase activity,...
Streptococcus pneumoniae resides in the oxygen-rich environment of upper respiratory tract, and therefore ability to survive presence oxygen is an important aspect its vivo survival. To investigate how S. adapts oxygen, we determined global gene expression profile micro-organism aerobiosis anaerobiosis. It was found that exposure elevated 54 genes, while 15 genes downregulated. Notably there were significant changes putative genome plasticity hypothetical genes. In addition, increased rgg ,...
Abstract Objectives The objective of this study was to determine the distribution and genetic basis trimethoprim resistance in Actinobacillus pleuropneumoniae isolates from pigs England. Methods Clinical collected between 1998 2011 were tested for sulphonamide. determined by shotgun WGS analysis subsequent isolation sequencing plasmids. Results A total 16 (out 106) A. resistant both (MIC >32 mg/L) sulfisoxazole ≥256 mg/L), a further 32 only mg/L). Genome sequence data...
Actinobacillus pleuropneumoniae is a mucosal respiratory pathogen causing contagious porcine pleuropneumonia. Pathogenesis studies have demonstrated major role for the capsule, exotoxins and outer membrane proteins. can also glycosylate proteins, using cytoplasmic N -linked glycosylating enzyme designated NGT, but its transcriptional arrangement in virulence remains unknown. We investigated NGT locus that putative unit consists of rimO , ngt glycosyltransferase termed agt. From this...
Campylobacter jejuni is the leading bacterial cause of human gastroenteritis worldwide and handling or consumption contaminated poultry meat key source infection. C. proteins FlpA SodB glycoconjugates containing N-glycan have been separately reported to be partially protective vaccines in chickens. In this study, two novel glycoproteins generated by protein glycan coupling technology—G-FlpA G-SodB (with three N-glycosylation sites, respectively)—were evaluated for efficacy against intestinal...
For the generation of energy, important human pathogen Streptococcus pneumoniae relies on host-derived sugars, including β-glucoside analogs. The catabolism these nutrients involves action 6-phospho-β-glucosidase to convert them into usable monosaccharaides. In this study, we characterized a (BglA3) encoded by SPD_0247. We found that enzyme has cell membrane localization and is active only against phosphorylated substrate. A mutated pneumococcal ΔSPD0247 strain had reduced...
Abstract Conjugate vaccines produced either by chemical or biologically conjugation have been demonstrated to be safe and efficacious in protection against several deadly bacterial diseases. However, conjugate vaccine assembly production shortcomings which hinders their wider availability. Here, we developed a tool, Mobile-element Assisted Glycoconjugation Insertion on Chromosome, MAGIC, novel biotechnological platform that overcomes the limitations of current design method(s). As model,...
Campylobacter is a major cause of acute gastroenteritis in humans, and infections can be followed by inflammatory neuropathies other sequelae. Handling or consumption poultry meat the primary risk factor for human campylobacteriosis, C. jejuni remains highly prevalent retail chicken many countries. Control avian reservoir expected to limit incidence disease. Toward this aim, we evaluated glycoconjugate vaccine comprising fibronectin-binding adhesin FlpA conjugated up ten moieties conserved...
To better understand Streptococcus pneumoniae pathogenesis we performed RNA sequencing on cerebrospinal fluid (CSF) from meningitis patients to identify bacterial genes expressed during invasion of the central nervous system. Comparison transcriptome data for serotype 1 S. cultured in ex vivo human CSF defined a subset 57 with high expression meningitis. Deletion two most highly genetic loci, bgaA (encodes beta-galactosidase) or SP_1801-5 putative stress response operon, resulted strains...
Abstract Background Poultry is the world's most popular animal-based food and global production has tripled in past 20 years alone. Low-cost vaccines that can be combined to protect poultry against multiple infections are a current imperative. Glycoconjugate vaccines, which consist of an immunogenic protein covalently coupled glycan antigens targeted pathogen, have proven track record human vaccinology, but yet used for livestock due prohibitively high manufacturing costs. To overcome this,...
ABSTRACT The RNA chaperone Hfq regulates diverse processes in numerous bacteria. In this study, we compared phenotypes (growth rate, adherence, response to different stress conditions and virulence Galleria mellonella) of wild-type (WT) isogenic hfq mutants three serovars (1, 8 15) the porcine pathogen Actinobacillus pleuropneumoniae. Similar growth rich broth was seen for all strains except Ap1∆hfq, which showed slightly reduced throughout 24 h time course, complemented Ap8∆hfqC mutant had...
Background Mortality from bacterial meningitis, predominately caused by Streptococcus pneumoniae , exceeds 50% in sub-Saharan African countries with high HIV prevalence. Underlying causes of mortality are poorly understood. We examined the host and pathogen proteome CSF adults proven pneumococcal meningitis (PM), testing if there was an association between differentially expressed proteins outcome. Materials/Methods proteomes were analyzed quantitative Mass-Spectrometry. Spectra identified...
Campylobacter is an animal and zoonotic pathogen of global importance, a pressing need exists for effective vaccines, including those that make use conserved polysaccharide antigens. To this end, we adapted Protein Glycan Coupling Technology (PGCT) to develop versatile Escherichia coli strain capable generating multiple glycoconjugate vaccine candidates against jejuni.We generated glycoengineering E. containing the C. jejuni heptasaccharide coding region integrated in its chromosome as model...
The porcine pathogen Streptococcus suis colonizes the upper respiratory tracts of pigs, potentially causing septicaemia, meningitis and death, thus placing a severe burden on agricultural industry worldwide. It is also zoonotic that known to cause systemic infections in humans. Understanding how S. interacts with its hosts relevant for future strategies drug vaccine development. As other Gram-positive bacteria, utilizes enzymes as sortases attach specific proteins bearing cell wall sorting...
An amendment to this paper has been published and can be accessed via a link at the top of paper.
Streptococcus pneumoniae capsular serotype 1 continues to pose a huge infectious disease burden in low- and middle-income countries, particularly West Africa. However, studies on this important have been hampered by the inability genetically modify these strains. In study we modified strain (519/43), first time that has achieved for serotype, providing methodology deeper understanding of its biology pathogenicity. As proof principle constructed defined pneumolysin mutant showed it lost...
Comprehensive identification of conditionally essential genes requires efficient tools for generating high-density transposon libraries that, ideally, can be analysed using next-generation sequencing methods such as Transposon Directed Insertion-site Sequencing (TraDIS). The Himar1 (mariner) is ideal near-saturating mutant libraries, especially in AT-rich chromosomes, the requirement integration a TA dinucleotide, and this has been used mutagenesis wide variety bacteria. However, plasmids...