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

Abstract

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 increasingly common in all settings. Whole genome sequencing (WGS) is increasingly utilised for S. sonnei outbreak investigation and surveillance, but comparison of data between studies and labs is challenging. Here, we present a genomic framework and genotyping scheme for S. sonnei to efficiently identify genotype and resistance determinants from WGS data. The scheme is implemented in the software package Mykrobe and tested on thousands of genomes. Applying this approach to analyse >4,000 S. sonnei isolates sequenced in public health labs in three countries identified several common genotypes associated with increased rates of ciprofloxacin resistance and azithromycin resistance, confirming intercontinental spread of highly-resistant S. sonnei clones and demonstrating the genomic framework can facilitate monitoring the spread of resistant clones, including those that have recently emerged, at local and global scales.

Acquisition and loss of CTX-M plasmids in Shigella species associated with MSM transmission in the UK

“…When utilising the standard typing scheme, 893 916 was part of the CipR.MSM5 sublineage (genotype 3.6.1.1.2), which emerged from South Asia in the early 2000s, is linked to MSM communities and is responsible for the majority of fluoroquinolone resistant S. sonnei infections in Australia, England and the USA [47].…”

“…This clade is known to have acquired pKSR100 (with erm(B ) and mph(A )) on multiple occasions, have single QRDR mutations and links to Australian MSM but has a declining effective population with stable case rates [ 45 ]. Lineage typing according to a new scheme denotes 598 080 and 607 387 to be part of the VN2.KH1.Aus lineage (genotype 3.7.29.1.4.1); Australian isolates that emerged from the Khanh Hoa region of Vietnam [ 47 ].…”

“…Members are known to harbour pKSR100 and concerning triple QRDR mutations (some exhibited an additional parC E84G mutation) and have an increasing effective population size since 2017 [ 45 ]. When utilising the standard typing scheme, 893 916 was part of the CipR.MSM5 sublineage (genotype 3.6.1.1.2), which emerged from South Asia in the early 2000s, is linked to MSM communities and is responsible for the majority of fluoroquinolone resistant S. sonnei infections in Australia, England and the USA [ 47 ].…”

“…Typing of S. sonnei isolates 598 080 and 607 387 determined them as VN2.KH1.Aus; Australian isolates emerging from Kahnh Hoa Subclone 1 [47]. Though not designated as MSM-linked by this scheme, this could represent travel-associated introduction into England and subsequent MSM transmission.…”

“…[ 8 ] and extracted directly from SnapperDB v0.2.5. To ensure greater utility to public health researchers, lineage typing of S. sonnei isolates (including publicly available AUSMDU00008333 (GenBank accession ERA1715196) and 183 660 (GenBank accession SRX1766927)) was also performed according to a newly described standard scheme [ 47 ] with Mykrobe v0.9.0 (predict) software [ 48 ] using the --ont parameter with trimmed FASTQ reads as input.…”