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Berrington, J. E.

Publications and source records attributed to Berrington, J. E..

3 recordsLinked to original sources

Staphylococcus haemolyticus Population Genomics Provides Insights into Pathogenicity and Commensalism

Staphylococcus haemolyticus is a common commensal bacterium but also an opportunistic pathogen, frequently implicated in bacteraemia and sepsis in preterm neonates and immunocompromised patients. Despite its clinical relevance, relatively little is known about the population structure of S. haemolyticus and how this relates to its ability to colonise humans or cause disease. In this study, we analysed commensal and clinical strains isolated from neonates and adults from 20 countries between 1957 - 2022. Whole genome sequencing of these isolates, combined with publicly available data, generated a comprehensive dataset of 986 genomes. This enabled us to characterise the species population structure and track the distribution of antimicrobial resistance (AMR) and virulence determinants. Our analysis revealed a highly diverse genome structure, with multiple phylogenetic groups showing distinct associations with commensalism or pathogenicity. We observed extensive variation in mobile genetic elements, prophages, and AMR genes, alongside increased carriage of plasmids and AMR genes over time. Furthermore, genes lined to metal homeostasis, detoxification, and oxidative stress tolerance were differently abundant between commensal and clinical isolates. This work provides the most detailed view to date of S. haemolyticus diversity, its evolutionary dynamics, and the genetic factors that may underpin the transition from commensal to pathogen.

genetics↗

Human milk oligosaccharide metabolism by Clostridium species suppresses inflammation and pathogen growth

Gut microbiome development is strongly impacted by breastmilk and human milk oligosaccharides (HMOs), with short- and long-term health implications. HMO metabolism is best characterised within bifidobacteria, but the full range of other HMO-utilising species remains unknown. This study examined HMO-utilising bacteria that colonise preterm infants (born <32 weeks gestation), their role in microbiome modulation, and their effects on intestinal barrier function. We found that infant-derived Clostridium perfringens, and three other Clostridium species, metabolise HMOs, producing short chain fatty acids, tryptophan catabolites, and other metabolites known to improve host health. C. perfringens inhibited pathobiont growth and supressed inflammation in preterm-derived intestinal organoids. These findings suggest a previously unrecognised role for C. perfringens, specifically those lacking the perfringolysin O gene, in promoting healthy gut development during infancy.

microbiology↗

Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown

The human gut microbiota (HGM) are closely associated with health, development and disease. The thick intestinal mucus layer, especially in the colon, is the key barrier between the contents of the lumen and the epithelial cells, providing protection against infiltration by the microbiota as well potential pathogens. The upper layer of the colonic mucus is a niche for a subset of the microbiota which utilise the mucin glycoproteins as a nutrient source and mucin grazing by the microbiota appears to play a key role in maintaining barrier function as well as community stability. Despite the importance of mucin breakdown for gut health, the mechanisms by which gut bacteria access this complex glycoprotein are not well understood. The current model for mucin degradation involves exclusively exo-acting glycosidases that sequentially trim monosaccharides from the termini of the glycan chains to eventually allow access to the mucin peptide backbone by proteases. However, this model is in direct contrast to the Sus paradigm of glycan breakdown used by the Bacteroidetes which involves extracellular cleavage of glycans by surface located endo-acting enzymes prior to import of the oligosaccharide products. Here we describe the discovery and characterisation of endo-acting family 16 glycoside hydrolases (GH16s) from prominent mucin degrading gut bacteria that specifically target the oligosaccharide side chains of intestinal mucins from both animals and humans. These endo-acting O-glycanases display {beta}1,4-glactosidase activity and in several cases are surface located indicating they are involved in the initial step in mucin breakdown. The data suggest a new paradigm for mucin breakdown by the microbiota and the endo-mucinases provide a potential tool to explore changes that occur in mucin structure in intestinal disorders such as inflammatory bowel disease and colon cancer.

biochemistry↗