Poster Presentation Society for Molecular Biology and Evolution Conference 2016

Identification of source and sink populations for the emergence and global spread of the East-Asia clone of Community-Associated MRSA (#613)

Melissa Ward 1 2 , Mariya Goncheva 3 , Emily Richardson 3 , Paul McAdam 3 , Emma Raftis 3 , Angela Kearns 4 , Robert Daum 5 , Michael David 5 , Tsai Ling Lauderdale 6 , Kirsty Girvan 7 , Giles Edwards 7 , Graeme Nimmo 8 , Xander Huijsdens 9 , Mark Woolhouse 1 , Ross Fitzgerald 3
  1. Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UK
  2. University of Oxford, Oxford, OXFORDSHIRE, United Kingdom
  3. The Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom
  4. Public Health England, Colindale, United Kingdom
  5. University of Chicago, Chicago, Illinois, USA
  6. National Health Research Institutes, Taiwan
  7. Scottish MRSA Reference Laboratory, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom
  8. Griffith University School of Medicine, Gold Coast, Queensland, Australia
  9. National Institute for Public Health and the Environment, Bilthoven, The Netherlands

Background

Our understanding of the factors influencing the emergence, dissemination and global distribution of epidemic clones of bacteria is very limited. ST59 is a major epidemic clone of community-associated MRSA in East Asia, responsible for extensive morbidity and mortality, but has a much lower prevalence in other parts of the world. The geographic origin of the ST59 clone and its international routes of dissemination are unclear and disputed in the literature.  

 

Results

To investigate the origin and spread of the ST59 clone, we obtained whole genome sequences of isolates from four continents, sampled over more than a decade, and carried out a time-scaled phylogeographic analysis.  We discovered that two distinct ST59 clades emerged concurrently, in Taiwan and the USA, but underwent clonal expansion at different times.  The Taiwan clade was strongly enriched for gene determinants associated with antibiotic resistance, consistent with regional differences in antibiotic usage.  Both clones spread independently to Australia and Europe and we found evidence of the persistence of multi-drug resistance following export from Taiwan.  Direct transfer of strains between Taiwan and the USA was not observed in either direction, consistent with geographic niche exclusion.   Unexpectedly, in vitro competitive fitness experiments revealed that ST59 strains from the Taiwan and USA clades were able to out-compete USA300, the dominant community-associated MRSA strain in the USA.

 

Conclusions

Our results resolve a longstanding controversy regarding the origin of the ST59 clone, revealing the major global source and sink populations and routes for the spread of multi-drug resistant clones.  In addition our findings indicate that the diversification of the accessory genome of epidemic clones partly reflects region-specific patterns of antibiotic usage, which may influence bacterial fitness after transmission to different geographic locations.