Typing of Staphylococcus aureus based on differentially variable target sequences results in consistency of strain relatedness

  • Damian Melles, Erasmus MC, University Medical Center Rotterdam, The Netherlands
  • Dr Leo Schouls, National Institute for Public Health and the Environment, The Netherlands
  • Dr Patrice François, University Hospitals of Geneva, Switzerland
  • Dr Sébastien Herzig, University Hospitals of Geneva, Switzerland
  • Prof dr Henri Verbrugh, Erasmus MC, University Medical Center Rotterdam, The Netherlands
  • Prof dr Alex van Belkum, Erasmus MC, University Medical Center Rotterdam, The Netherlands
  • Prof dr Jacques Schrenzel, University Hospitals of Geneva, Switzerland
  • Objective: It is generally assumed that, in bacteria, genetic variation in functionally constrained genomic regions accumulates at a lower rate than in regions of hypermutability such as DNA repeat loci. Data obtained by different genome screening methods, focusing on constraint versus hypermutable regions, for a large collection of bacterial isolates have rarely been linked in order to compare the assignment of genetic types. In this study we provide an example of such an analysis.
    Methods: We compared whole genome polymorphism (using high-throughput amplified fragment length polymorphism [ht-AFLP]) as well as short sequence repeat length variation (using multi-locus variable number of tandem repeat analysis [MLVA]) for 994 Staphylococcus aureus strains isolated from both healthy carriers and invasive infections.
    Results: MLVA and ht-AFLP trees showed similar population structures despite measuring totally different types of genetic events. This strengthens the population structure model and suggests that, despite the enhanced variability of repeats, clusters of strains remains traceable. Finally, no specific molecular marker of epidemicity or virulence was identified in this large strain collection by either genome typing technology.
    Conclusions: We demonstrate that there is a difference in the rates of cross-genome mutation versus regional repeat variability in the clonal bacterial pathogen S. aureus. However, despite these dynamic differences, a conservation of type assignments as based upon these two inherently different typing techniques was observed. In other words, measuring repeat polymorphisms in clonal microorganisms provides a solid basis for genetic type assignment useful for application in epidemiological tracing.