Clonal differences in Staphylococcus aureus bacteraemia-associated mortality

Mario Recker, Maisem Laabei, Michelle S. Toleman, Sandra Reuter, Rebecca B. Saunderson, Beth Blane, M. Estee Török, Khadija Ouadi, Emily Stevens, Maho Yokoyama, Joseph Steventon, Luke Thompson, Gregory Milne, Sion Bayliss, Leann Bacon, Sharon J Peacock, Ruth C. Massey

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

Abstract

The bacterium Staphylococcus aureus is a major human pathogen for which the emergence of antibiotic resistance is a global public health concern. Infection severity, and in particular bacteraemia-associated mortality, has been attributed to several host-related factors, such as age and the presence of comorbidities. The role of the bacterium in infection severity is less well understood, as it is complicated by the multifaceted nature of bacterial virulence, which has so far prevented a robust mapping between genotype, phenotype and infection outcome. To investigate the role of bacterial factors in contributing to bacteraemia-associated mortality, we phenotyped a collection of sequenced clinical S. aureus isolates from patients with bloodstream infections, representing two globally important clonal types, CC22 and CC30. By adopting a genome-wide association study approach we identified and functionally verified several genetic loci that affect the expression of cytolytic toxicity and biofilm formation. By analysing the pooled data comprising bacterial genotype and phenotype together with clinical metadata within a machine-learning framework, we found significant clonal differences in the determinants most predictive of poor infection outcome. Whereas elevated cytolytic toxicity in combination with low levels of biofilm formation was predictive of an increased risk of mortality in infections by strains of a CC22 background, these virulence-specific factors had little influence on mortality rates associated with CC30 infections. Our results therefore suggest that different clones may have adopted different strategies to overcome host responses and cause severe pathology. Our study further demonstrates the use of a combined genomics and data analytic approach to enhance our understanding of bacterial pathogenesis at the individual level, which will be an important step towards personalized medicine and infectious disease management.

Original languageEnglish
Pages (from-to)1381-1388
Number of pages8
JournalNature Microbiology
Volume2
Issue number10
Early online date7 Aug 2017
DOIs
Publication statusPublished - 1 Oct 2017

ASJC Scopus subject areas

  • Microbiology
  • Applied Microbiology and Biotechnology
  • Immunology
  • Microbiology (medical)
  • Cell Biology
  • Genetics

Fingerprint

Dive into the research topics of 'Clonal differences in <i>Staphylococcus aureus</i> bacteraemia-associated mortality'. Together they form a unique fingerprint.

Cite this