Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2021

Global population structure and genotyping framework for genomic surveillance of the major dysentery pathogen, Shigella sonnei (#122)

Jane Hawkey 1 , Kalani Paranagama 1 , Kate S Baker 2 , Rebecca J Bengtsson 2 , François-Xavier Weill 3 , Nicholas R Thomson 4 5 , Stephen Baker 6 7 , Louise Cerdeira 1 , Zamin Iqbal 8 , Martin Hunt 8 9 , Danielle J Ingle 10 11 , Timothy J Dallman 12 , Claire Jenkins 12 , Deborah A Williamson 10 13 , Kathryn E Holt 1 5
  1. Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, VIC, Australia
  2. Department of Clinical Infection, Microbiology, and Immunology, Institute for Infection, Ecological and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom
  3. Unité des Bactéries Pathogènes Entériques, Centre National de Référence des Escherichia coli, Shigella et Salmonella, Institut Pasteur, Paris, France
  4. Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
  5. Dept Infection Biology, London School of Hygiene & Tropical Medicine, London, United Kingdom
  6. University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, United Kingdom
  7. Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, United Kingdom
  8. European Molecular Biology Laboratory , European Bioinformatics Institute, Hinxton, United Kingdom
  9. Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
  10. Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Vic, Australia
  11. Research School of Population Health, Australia National University, Canberra, ACT, Australia
  12. National Infection Service, Public Health England, London, United Kingdom
  13. Department of Microbiology, Royal Melbourne Hospital, Melbourne, Vic, Australia

Shigella sonnei is the most common agent of shigellosis in high-income countries, and causes a significant disease burden in low- and middle-income countries. Antimicrobial resistance is progressively common in all settings. Whole genome sequencing (WGS) is increasingly utilised for S. sonnei outbreak investigation and surveillance by public health labs, but comparison of data between studies and labs is challenging. To determine lineage from WGS data, most labs undergo the time-consuming process of downloading public reference genome data, constructing whole genome alignments, and inferring phylogenies. Most studies to date report which of the five major lineages their isolates belong to, but studies of S. sonnei isolates from men who have sex with men (MSM) in different countries have designated different names for the same lineages, obscuring the fact that the same clones are spreading amongst MSM communities in different countries. However, genotyping frameworks based on single nucleotide variants (SNVs) that enable fast and accurate typing of clinical isolates from WGS data have been widely adopted for other bacterial pathogens, facilitating straightforward identification and cross-jurisdictional communication about epidemiologically important lineages.

Here, we describe the global population structure of S. sonnei using 1,935 globally distributed genomes and use these to define a hierarchical SNV-based genotyping scheme. We validated our scheme with an additional 2,015 genomes from the public GenomeTrakr database and implemented it within the free and open-source software, Mykrobe. We analysed 4,222 S. sonnei isolates sequenced in public health labs from 2016 – 2019 in Victoria (Australia), England, and the USA, and identified several common genotypes associated with increased rates of ciprofloxacin resistance and azithromycin resistance, confirming intercontinental spread of highly-resistant S. sonnei clones. A universal nomenclature for S. sonnei provides a structure to enable clear communication between public health and basic science research groups and aids monitoring of the emergence and spread of resistant S. sonnei clones at both local and global levels.