1887

Abstract

is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in were significantly associated with bacteraemia-vs-carriage (10-10). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of (HMP=10) as well as the presence of SCCmec (HMP=10). Among carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein , where kmers representing conserved sequence allele were associated with CA carriage (10-10), while in , a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (10). In an extensive study of bacteraemia and nasal carriage in the UK, we found strong evidence that all lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein is a novel genomic marker of healthcare origin in but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease.

Funding
This study was supported by the:
  • wellcome trust (Award Grant 101611/Z/13/Z)
    • Principle Award Recipient: BernadetteC Young
  • wellcome trust (Award Grant 101237/Z/13/B)
    • Principle Award Recipient: DanielJ Wilson
  • wellcome trust (Award 203141/Z/16/Z)
    • Principle Award Recipient: NotApplicable
  • department of health (Award grant HICF-T5-358)
    • Principle Award Recipient: NotApplicable
  • wellcome trust (Award WT098615/Z/12/Z)
    • Principle Award Recipient: NotApplicable
  • national institute for health research (Award HPRU-2012-10041)
    • Principle Award Recipient: NotApplicable
  • fondation mérieux
    • Principle Award Recipient: DanielJ Wilson
  • nihr oxford biomedical research centre
    • Principle Award Recipient: NotApplicable
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2021-12-04
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