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dc.contributor.advisorHolden, Matthew
dc.contributor.advisorGillespie, S. H.
dc.contributor.advisorTempleton, Kate
dc.contributor.authorMcHugh, Martin Patrick
dc.description.abstractEnterococcus faecium and Enterococcus faecalis are important causes of healthcare-associated infections in immunocompromised patients. Enterococci thrive in modern healthcare settings, being able to resist killing by a range of antimicrobial agents, persist in the environment, and adapt to changing circumstances. In Scotland, rates of vancomycin resistant E. faecium (VREfm) have risen almost 150% in recent years leaving few treatment options and challenging healthcare delivery. Resistance to the last line agent linezolid has also been detected in E. faecalis. Whole genome sequencing (WGS) allows investigation of the population structure and transmission of microorganisms, and identification of antimicrobial resistance mechanisms. The aim of this thesis was to use WGS to understand the molecular epidemiology of antimicrobial resistant enterococci from human healthcare settings in Scotland. Analysis of some of the earliest identified Scottish linezolid-resistant E. faecalis showed the resistance mechanism, optrA, was present in unrelated lineages and in different genetic elements, suggesting multiple introductions from a larger reservoir. To inform transmission investigations, within-patient diversity of VREfm was explored showing ~30% of patients carried multiple lineages and identifying a within-patient diversity threshold for transmission studies. WGS was then applied to a large nosocomial outbreak of VREfm, highlighting a complex network of related variants across multiple wards. Having examined within-hospital transmission, the role of regional relationships was investigated which showed that VREfm in Scotland is driven by multiple clones transmitted within individual Health Boards with occasional spread between regions. The most common lineage in the national collection (ST203) was estimated to have been present in Scotland since around 2005, highlighting its persistence in the face of increasing infection prevention and control measures. This thesis provides a starting point for genomic surveillance of enterococci in Scotland, and a basis for interventional studies aiming to reduce the burden of enterococcal infections.en_US
dc.description.sponsorship"This work was supported by the Chief Scientist Office (Scotland) [grant number SIRN/10]; the Wellcome Trust [grant numbers 105621/Z/14/Z, 206194]; and the BBSRC [grant number BB/S019669/1]."—Fundingen
dc.relationMcHugh, M. P., Parcell, B. J., Pettigrew, K. A., Toner, G., Khatamzas, E., el Sakka, N., Karcher, A. M., Walker, J., Weir, R., Meunier, D., Hopkins, K. L., Woodford, N., Templeton, K. E., Gillespie, S. H., & Holden, M. T. G. (2022). Presence of optrA-mediated linezolid resistance in multiple lineages and plasmids of Enterococcus faecalis revealed by long read sequencing. Microbiology, 168(2), Article 001137. [ : Open Access version]en
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 International*
dc.subjectEnterococcus faeciumen_US
dc.subjectEnterococcus faecalisen_US
dc.subjectLinezolid resistanceen_US
dc.subjectVancomycin resistanceen_US
dc.subjectWhole genome sequencingen_US
dc.subjectVancomycin resistant enterococcusen_US
dc.subjectAntimicrobial resistanceen_US
dc.subjectHealthcare associated infectionen_US
dc.titleGenomic investigation of antimicrobial resistant enterococcien_US
dc.contributor.sponsorChief Scientist Office, Scottish Governmenten_US
dc.contributor.sponsorWellcome Trusten_US
dc.contributor.sponsorBiotechnology and Biological Sciences Research Council (BBSRC)en_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US
dc.publisher.departmentNHS Lothianen_US
dc.identifier.grantnumber105621/Z/14/Z, 206194en_US

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