Characterising Staphylococcus aureus genomic epidemiology with Multilevel Genome Typing.

Staphylococcus aureus is a major source of both hospital and community acquired infections, and is the leading source of skin and soft tissue infections worldwide. Advances in whole genome sequencing (WGS) technologies have recently generated large volumes of S. aureus WGS data. The timely classification of S. aureus WGS data with genomic typing technologies has the potential to describe detailed genomic epidemiology at large and small scales. In this study, a multilevel genome typing (MGT) scheme comprised of 8 levels of multilocus sequence typing schemes of increasing resolution was developed for S. aureus and used to analyse 50,481 publicly available genomes. Application of MGT to S. aureus epidemiology was showcased in three case studies. Firstly, the population structure of the globally disseminated sequence type ST8 were described by MGT2, which was compared with Spa typing. Secondly, MGT was used to characterise MLST ST8 - PFGE USA300 isolates that colonised multiple body sites of the same patient. Unique STs from multiple MGT levels were able to group isolates of the same patient, and the highest resolution MGT8 separated isolates within a patient that varied in predicted antimicrobial resistance. Lastly, MGT was used to describe the transmission of MLST ST239 - SCCmec III throughout a single hospital. MGT STs were able to describe both isolates that had spread between wards and also isolates that had colonised different reservoirs within a ward. The S. aureus MGT describes large- and small-scale S. aureus genomic epidemiology with scalable resolutions using stable and standardised ST assignments. The S. aureus MGT database is online (https://mgtdb.unsw.edu.au/staphylococcus) and is capable of tracking new and existing clones to facilitate the design of new strategies to reduce the global burden of S. aureus related diseases.