Biochemistry and Pharmacology - Research Publications

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Author: Edwards, David × Author: Holt, Kathryn × Author: Wyres, Kelly × End date: 2019 × Start date: 2010 × Type: Journal Article ×

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    Extensive Capsule Locus Variation and Large-Scale Genomic Recombination within the Klebsiella pneumoniae Clonal Group 258
    Wyres, KL ; Gorrie, C ; Edwards, DJ ; Wertheim, HFL ; Hsu, LY ; Nguyen, VK ; Zadoks, R ; Baker, S ; Holt, KE (OXFORD UNIV PRESS, 2015-05)
    Klebsiella pneumoniae clonal group (CG) 258, comprising sequence types (STs) 258, 11, and closely related variants, is associated with dissemination of the K. pneumoniae carbapenemase (KPC). Hospital outbreaks of KPC CG258 infections have been observed globally and are very difficult to treat. As a consequence, there is renewed interest in alternative infection control measures such as vaccines and phage or depolymerase treatments targeting the K. pneumoniae polysaccharide capsule. To date, 78 immunologically distinct capsule variants have been described in K. pneumoniae. Previous investigations of ST258 and a small number of closely related strains suggested that capsular variation was limited within this clone; only two distinct ST258 capsule polysaccharide synthesis (cps) loci have been identified, both acquired through large-scale recombination events (>50 kb). In contrast to previous studies, we report a comparative genomic analysis of the broader K. pneumoniae CG258 (n = 39). We identified 11 different cps loci within CG258, indicating that capsular switching is actually common within the complex. We observed several insertion sequences (IS) within the cps loci, and show further intraclone diversification of two cps loci through IS activity. Our data also indicate that several large-scale recombination events have shaped the genomes of CG258, and that definition of the complex should be broadened to include ST395 (also reported to harbor KPC). As only the second report of extensive intraclonal cps variation among Gram-negative bacterial species, our findings alter our understanding of the evolution of these organisms and have key implications for the design of control measures targeting K. pneumoniae capsules.
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    A platform for leveraging next generation sequencing for routine microbiology and public health use
    Rusu, LI ; Wyres, KL ; Reumann, M ; Queiroz, C ; Bojovschi, A ; Conway, T ; Garg, S ; Edwards, DJ ; Hogg, G ; Holt, KE (BIOMED CENTRAL LTD, 2015-12)
    Even with the advent of next-generation sequencing (NGS) technologies which have revolutionised the field of bacterial genomics in recent years, a major barrier still exists to the implementation of NGS for routine microbiological use (in public health and clinical microbiology laboratories). Such routine use would make a big difference to investigations of pathogen transmission and prevention/control of (sometimes lethal) infections. The inherent complexity and high frequency of data analyses on very large sets of bacterial DNA sequence data, the ability to ensure data provenance and automatically track and log all analyses for audit purposes, the need for quick and accurate results, together with an essential user-friendly interface for regular non-technical laboratory staff, are all critical requirements for routine use in a public health setting. There are currently no systems to answer positively to all these requirements, in an integrated manner. In this paper, we describe a system for sequence analysis and interpretation that is highly automated and tackles the issues raised earlier, and that is designed for use in diagnostic laboratories by healthcare workers with no specialist bioinformatics knowledge.