A5053685021- Bacterial Infections and Vaccines
- Clostridium difficile and Clostridium perfringens research
- Microscopic Colitis
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Microbial infections and disease research
- Viral gastroenteritis research and epidemiology
- Pneumonia and Respiratory Infections
- RNA and protein synthesis mechanisms
- Chromosomal and Genetic Variations
- Neurobiology and Insect Physiology Research
- Veterinary medicine and infectious diseases
- Plant Molecular Biology Research
- Microbial Metabolic Engineering and Bioproduction
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Phylogenetic Studies
- Probiotics and Fermented Foods
- Immunotherapy and Immune Responses
- Chemical Reactions and Isotopes
- Animal Virus Infections Studies
- Animal Behavior and Reproduction
- Antibiotic Resistance in Bacteria
- Gut microbiota and health
- Bacterial Genetics and Biotechnology
- Microbial Metabolites in Food Biotechnology
University of Nottingham
2019-2025
Nottingham Biomedical Research Centre
2021-2025
Nottingham University Hospitals NHS Trust
2021-2025
NIHR Nottingham Digestive Diseases Biomedical Research Unit
2021
University of Turku
2016
Kingston University
2015-2016
Université Grenoble Alpes
2014
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2014
Centre National de la Recherche Scientifique
2014
Inserm
2014
Glycosylated p-hydroxybenzoic acid methyl esters and structurally related phenolphthiocerol glycolipids are important virulence factors of Mycobacterium tuberculosis. Although both types molecules thought to be derived from acid, the origin this putative biosynthetic precursor in mycobacteria remained established. We describe characterization a transposon mutant M. tuberculosis deficient production all forms derivatives. The was found inserted Rv2949c, gene located vicinity polyketide...
ABSTRACT Using signature-tagged transposon mutagenesis, we isolated 23 Mycobacterium tuberculosis mutants, corresponding to 21 genes or genetic regions, attenuated in their ability parasitize human macrophages. Mutants disrupted the ABC transporter-encoding Rv0986 and Rv0987 were further characterized as being impaired bind host cells.
Clostridium butyricum ferments non-digested dietary fibre in the colon to produce butyric acid. Butyrate is a four-carbon, short-chain fatty acid (SCFA) which has multiple health benefits. Many microbial products of pharmaceutical or industrial interest, such as butyrate, are produced low quantities due rate-limiting steps their metabolic pathway, including abundance activity one more enzymes pathway. By identifying former, appropriate can be over-expressed increase product yields, however,...
Fecal microbiota transplantation (FMT) is highly effective in recurrent
Clostridioides difficile is an opportunistic gut pathogen which causes severe colitis, leading to significant morbidity and mortality due its toxins, TcdA TcdB. Two intra-muscular toxoid vaccines entered Phase III trials strongly induced toxin-neutralising antibodies systemically but failed provide local protection in the colon from primary C. infection (CDI). Alternatively, by immunising orally, ileum (main immune inductive site) can be directly targeted confer large intestine. The...
The level of cell surface expression the meningococcal vaccine antigen, Factor H binding protein (FHbp) varies between and within strains this limits breadth that can be targeted by FHbp-based vaccines. molecular pathway controlling FHbp at surface, including its lipidation, sorting to outer membrane export, potential regulation have not been investigated until now. This knowledge will aid our evaluation vaccines.A transposon library was screened whole immuno-dot blotting using an anti-FHbp...
Meningococcal lipoprotein, Factor H binding protein (FHbp), is the sole antigen of Trumenba vaccine (Pfizer) and one four antigens Bexsero (GSK) targeting Neisseria meningitidis serogroup B isolates. Lipidation FHbp assumed to occur for all We show in 91% a collection UK isolates (1742/1895) non-synonymous single nucleotide polymorphisms (SNPs) signal peptide FHbp. A SNP, common all, alters polar amino acid that abolishes processing: lipidation cleavage. Whilst some precursor retained...
The locus lex2 , comprising lex2A and lex2B contributes to the phase-variable expression of lipopolysaccharide (LPS) Haemophilus influenzae was found be present in 74 % strains investigated. contains 5′-GCAA repeats which vary number from 4 46 copies between strains. cloned serotype b RM7004 RM153 showed >99 nucleotide sequence identity these published sequence. Disruption gene strain resulted truncation some LPS glycoforms, shown by gel fractionation, with only one glycoform reacting a...
ABSTRACT Digalactoside (galα-1-4 galβ) structures of the lipopolysaccharide (LPS) Haemophilus influenzae are implicated in virulence. A confounding factor is that tetranucleotide repeats within lic2A , lgtC and lex2 genes mediate phase-variable expression digalactosides. By deleting these repeats, we constructed recombinant strains RM153 constitutively expressing either one or two LPS Expression digalactosides, rather than one, was associated with increased virulence H. vivo.
Clostridioides difficile is the main cause of health-care-associated infectious diarrhoea. Toxins, TcdA and TcdB, secreted by this bacterium damage colonic epithelial cells in severe cases culminates pseudomembranous colitis, toxic megacolon death. Vaccines human trials have focused exclusively on parenteral administration toxin-based formulations. These vaccines promote toxin-neutralising serum antibodies but fail to confer protection from infection gut. An effective route immunise against...
The phase-variable locus lex2 is required for expression of a Haemophilus influenzae lipopolysaccharide (LPS) epitope previously unknown structure. This epitope, which reactive with monoclonal antibody (MAb) 5G8, has been associated virulence type b strains. When strain RM118 (from the same source as Rd), in and MAb 5G8 reactivity are absent, was transformed DNA, transformants that were obtained. Surprisingly, these phase variable, although lacked tetrameric repeats constitutively expressed....
Mucosal vaccination aims to prevent infection mainly by inducing secretory IgA (sIgA) antibody, which neutralises pathogens and enterotoxins blocking their attachment epithelial cells. We previously demonstrated that encapsulated protein antigen CD0873 given orally hamsters induces neutralising antibodies locally as well systemically, affording partial protection against Clostridioides difficile infection. The aim of this study was determine whether displaying on liposomes, mimicking native...
Male fitness is dependent on sexual traits that influence mate acquisition (precopulatory selection) and paternity (post-copulatory selection), although many studies have documented the form of selection in one or other these arenas, fewer done it for both. Nonetheless, appears dominant directional, theoretically, populations should converge peaks surface, where stabilizing. Many factors, however, can prevent from reaching adaptive peaks. Genetic constraints be important if they development...
Here, we describe the draft sequence of a virulent isolate Neisseria meningitidis strain L91543, belonging to serogroup C. The findings from previous proteomic and metabolomic studies this can now be further interpreted with genomic analysis. Comparative analysis genome revealed close similarity localized synteny N. C strain, FAM18. Polymorphisms were identified in signal peptide factor H binding protein, target for new meningococcal vaccines, which may result its inefficient translocation...
Oral vaccines, unlike injected, induce intestinal secretory immunoglobulin A (sIgA) mimicking our natural defense against gut pathogens. We previously observed sIgA responses after administering the Clostridioides difficile colonisation factor CD0873 orally in enteric capsules to hamsters. Enteric-coated are designed resist dissolution stomach and disintegrate only at higher pH of small intestine. However, variable between animals led us speculate suboptimal transit antigens The rate gastric...
SUMMARY Complement-fixation tests were used to compare strains of Mycoplasma mycoides var. (5 strains), M. capri strains) and laidlawii bovine genital origin (3 strains). Strains showed cross-reactions about 25% identity, but appeared be antigenically distinct. The results, measured in terms the amounts complement fixed, are shown graphically discussed relation diagnosis contagious pleuropneumonia.
Abstract Meningococcal surface lipoprotein, Factor H binding protein (FHbp), is the sole antigen of Trumenba vaccine (Pfizer) and one four antigens Bexsero (GSK) targeting Neisseria meningitidis serogroup B isolates. Lipidation FHbp assumed to occur for all isolates its localisation conducted by lipoprotein assembly modulator, Slam. We show in 91% a collection UK (1742/1895) non-synonymous single nucleotide polymorphisms (SNPs) signal peptide FHbp. A SNP, common all, alters polar amino acid...
Abstract Butyrate is a short chain fatty acid with important industrial applications produced by chemical synthesis. With consumer demand for green products, the fermentative production of butyric microorganisms such as Clostridium attracting interest. butyricum ferments non-digested dietary fibre in colon to produce butyrate which has multiple health benefits, and certain strains are exploited probiotics, MIYAIRI588 (CBM588). Knowledge genes encoding enzymes involved determining those that...