A5039593333- Glycosylation and Glycoproteins Research
- Bacteriophages and microbial interactions
- Escherichia coli research studies
- Viral gastroenteritis research and epidemiology
- Salmonella and Campylobacter epidemiology
- Genomics and Phylogenetic Studies
- Pneumonia and Respiratory Infections
- Streptococcal Infections and Treatments
- Enzyme Production and Characterization
- Bacterial Genetics and Biotechnology
- Monoclonal and Polyclonal Antibodies Research
- Neonatal and Maternal Infections
- Viral Infections and Vectors
- Biochemical and Structural Characterization
- Music Technology and Sound Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Insect symbiosis and bacterial influences
- Bacterial Infections and Vaccines
- Peptidase Inhibition and Analysis
- Vibrio bacteria research studies
- Mosquito-borne diseases and control
- Antibiotic Resistance in Bacteria
London School of Hygiene & Tropical Medicine
2015-2025
University of London
2012-2021
Advances in genomics and mass spectrometry have revealed several types of glycosylation systems bacteria. However, why bacterial proteins are modified remains poorly defined. Here, we investigated the role general N- linked a major food poisoning bacterium, Campylobacter jejuni . The aim this study is to delineate direct indirect effects caused by disrupting posttranslational modification. To achieve this, employed quantitative proteomic strategy monitor alterations C. proteome. Our results...
Abstract Group A Streptococcus (Strep A) is a human-exclusive bacterial pathogen killing annually more than 500,000 patients, and no current licensed vaccine exists. Strep bacteria are highly diverse, but all produce an essential, abundant, conserved surface carbohydrate, the Carbohydrate, which contains rhamnose polysaccharide (RhaPS) backbone. RhaPS validated universal candidate in glycoconjugate prepared by chemical conjugation of native carbohydrate to carrier protein. We engineered...
Streptococcus pneumoniae is the leading cause of bacterial pneumonia. Although this a vaccine preventable disease, S. still causes over 1 million deaths per year, mainly in children under age five. The biggest disease burden developing world, which due to unavailability vaccines their high costs. Protein polysaccharide conjugate are given routinely developed world induce protective antibody response against pneumoniae. One these Prevnar13, targets 13 95 known capsular types. Current...
Nearly all bacterial species have at least a single glycosylation system, but the direct effects of these posttranslational protein modifications are unresolved. Glycoproteome-wide analysis several pathogens has revealed general glycan virulence factors and assemblies. Using Campylobacter jejuni as model organism, we studied role N- linked glycans in multidrug efflux pump commonly found Gram-negative bacteria. We show, for first time, link between N -linked activity. At level, demonstrate...
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...
Bacterial N-linking oligosaccharyl transferases (OTase enzymes) transfer lipid-linked glycans to selected proteins in the periplasm and were first described intestinal pathogen Campylobacter jejuni, a member of ε-proteobacteria-subdivision bacteria. More recently, orthologues from other ε-proteobacterial Helicobacter species δ-proteobacterium, Desulfovibrio desulfuricans, have been described, suggesting that these two subdivisions bacteria may be source further N-linked protein glycosylation...
Abstract Glycoengineering of recombinant glycans and glycoconjugates is a rapidly evolving field. However, the production exploitation has lagged behind that proteins nucleic acids. Biosynthetic glycoconjugate requires coordinated cooperation three key components within bacterial cell: substrate protein, coupling oligosaccharyltransferase, glycan biosynthesis locus. While acceptor protein oligosaccharyltransferase are products single genes, product multigene metabolic pathway. Typically,...
ABSTRACT Strep A is a human-exclusive bacterial pathogen killing annually more than 500,000 patients, and no current licensed vaccine exists. bacteria are highly diverse, but all produce an essential, abundant, conserved surface carbohydrate, the Group Carbohydrate, which contains rhamnose polysaccharide (RhaPS) backbone. RhaPS validated universal candidate in glycoconjugate prepared by chemical conjugation of native carbohydrate to carrier protein. We engineered Carbohydratte biosynthesis...
Abstract The application of bacterial oligosaccharyltransferases (OSTs) such as the Campylobacter jejuni PglB for glycoengineering has attracted considerable interest in and glycoconjugate vaccine development. However, limited specificity glycans that can be transferred to candidate proteins, which along with other factors is dependent on reducing end sugar glycans. In this study, we developed a cell‐free glycosylation assay offers speed simplicity ‘yes’ or ‘no’ determination. Using assay,...
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,...
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 Campylobacter jejuni is a commensal bacterium in the intestines of animals and birds major cause food-borne gastroenteritis humans worldwide. Here we show that exposure to pancreatic amylase leads secretion an α-dextran by C. secreted protease, Cj0511, required. Exposure promotes biofilm formation vitro , increases interaction with human epithelial cell lines, virulence Galleria mellonella infection model, colonization chicken ileum. We also protects from stress conditions...
Zika virus (ZIKV) is one of several examples an unprecedented pandemic spread and against which there currently no suitable vaccine or treatment. Here, we constructed characterized recombinant baculovirus-derived ZIKV-like particles (Zika VLPs) to study ZIKV-antibody interactions. These VLPs, uniquely consisted the full-length ZIKV capsid (C), pre-membrane (prM), envelope (E) proteins with either: a) viral nonstructural NS2B NS3 protease unit under two different promoters b) alternative...
Abstract Antimicrobial resistance (AMR) is threatening the lives of millions worldwide. Antibiotics which once saved countless lives, are now failing, ushering in vaccines development as a current global imperative. Conjugate produced either by chemical synthesis or biologically Escherichia coli cells, have been demonstrated to be safe and efficacious protection against several deadly bacterial diseases. However, conjugate assembly production shortcomings hinders their wider availability....
Abstract It is now apparent that nearly all bacteria species have at least a single glycosylation system, but the direct effect(s) of these protein post translational modifications are unresolved. In this study, we used general N -linked pathway from Campylobacter jejuni to investigate biophysical roles modification on CmeABC multidrug efflux pump complex. The study reveals multifunctional role glycans in enhancing thermostability, stabilising complexes and promotion protein-protein...