Publications by authors named "Thomas D Stanton"

Hypervirulent (hvKp) and classical multidrug-resistant (MDR) strains belong to distinct lineages and hvKp are typically characterized by hypermucoid capsules that have been shown to limit horizontal gene transfer (HGT), including plasmid acquisition. However, the convergence of hypervirulence and MDR is increasingly common worldwide. When we profiled 127 antibiotic-susceptible hvKp strains, we found that most (86%) are highly permissive to plasmid transfer despite their capsules.

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Surface polysaccharides are common antigens in priority pathogens and therefore attractive targets for novel control strategies such as vaccines, monoclonal antibody and phage therapies. Distinct serotypes correspond to diverse polysaccharide structures that are encoded by distinct biosynthesis gene clusters; e.g.

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Klebsiella pneumoniae is the leading cause of neonatal sepsis, strongly associated to antimicrobial resistance, with no vaccine available. K-antigens (KAg) have been identified as potential targets, but their diversity makes vaccine development challenging. Alternatively, the use of subcapsular O-antigens (OAg) raises questions about antibodies accessibility.

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Unlabelled: Sequencing DNA directly from patient samples enables faster pathogen characterization compared to traditional culture-based approaches, but often yields insufficient sequence data for effective downstream analysis. CRISPR-Cas9 enrichment is designed to improve the yield of low abundance sequences but has not been thoroughly explored with Oxford Nanopore Technologies (ONT) for use in clinical bacterial epidemiology. We designed CRISPR-Cas9 guide RNAs to enrich the human pathogen , by targeting multi-locus sequence type (MLST) and transfer RNA (tRNA) genes, as well as common antimicrobial resistance (AMR) genes and the resistance-associated integron gene .

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Oxford Nanopore Technologies (ONT) sequencing has rich potential for genomic epidemiology and public health investigations of bacterial pathogens, particularly in low-resource settings and at the point of care, due to its portability and affordability. However, low base-call accuracy has limited the reliability of ONT data for critical tasks such as antimicrobial resistance (AMR) and virulence gene detection and typing, serotype prediction, and cluster identification. Thus, Illumina sequencing remains the standard for genomic surveillance despite higher capital and running costs.

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