Genomic epidemiology of Shigella in the United Kingdom shows transmission of pathogen sublineages and determinants of antimicrobial resistance

Abstract

Shigella are globally important diarrhoeal pathogens that are endemic in low-to-middle income nations and also occur in high income nations, typically in travellers or community-based risk-groups. Shigella phylogenetics reveals population structures that are more reliable than those built with traditional typing methods, and has identified sublineages associated with specific geographical regions or patient groups. Genomic analyses reveal temporal increases in Shigella antimicrobial resistance (AMR) gene content, which is frequently encoded on mobile genetic elements. Here, we whole genome sequenced representative subsamples of S. flexneri 2a and S. sonnei (n = 366) from the United Kingdom from 2008 to 2014, and analysed these alongside publicly available data to make qualitative insights on the genomic epidemiology of shigellosis and its AMR within the broader global context. Combined phylogenetic, epidemiological and genomic anlayses revealed the presence of domestically-circulating sublineages in patient risk-groups and the importation of travel-related sublineages from both Africa and Asia, including ciprofloxacin-resistant sublineages of both species from Asia. Genomic analyses revealed common AMR determinants among travel-related and domestically-acquired isolates, and the evolution of mutations associated with reduced quinolone susceptibility in domestically-circulating sublineages. Collectively, this study provides unprecedented insights on the contribution and mobility of endemic and travel-imported sublineages and AMR determinants responsible for disease in a high-income nation.

The importance of public health genomics for ensuring health security for Australia

“…For example, when applied to surveillance of Shiga toxin‐producing Escherichia coli serotype O157, whole genome sequencing detected twice as many disease clusters than traditional typing methods, including common source outbreaks that were geographically distributed across the country . Similarly, routine whole genome sequencing of Salmonella enterica and Shigella isolates in England and Wales has generated a rich repository of genomic data, providing unparalleled levels of strain discrimination and a wealth of information on the emergence and spread of antimicrobial‐resistant pathogens …”

“…8 Similarly, routine whole genome sequencing of Salmonella enterica and Shigella isolates in England and Wales has generated a rich repository of genomic data, providing unparalleled levels of strain discrimination and a wealth of information on the emergence and spread of antimicrobial-resistant pathogens. 9,10…”

Persistent transmission of shigellosis in England is associated with a recently emerged multi-drug resistant strain ofShigella sonnei

“…Genome-derived serotyping and AMR-conferring genes and SNPs was performed using the GeneFinder tool (https://github.com/phe-bioinformatics/gene_finder) [21,28]. Resistance to streptomycin, tetracycline, the sulphonamides and trimethoprim in Shigella species is high, and trends have been consistent for many years [5,[15][16][17]28]. We therefore focused our AMR analysis on the presence of genomic makers of resistance to macrolides (specifically ermB and mphA) and fluroquinolones (specifically mutations in the quinolones resistance determining regions (QRDR) of gyrA and parC), as the trends in resistance to these clinically relevant classes of antimicrobials fluctuated during the study period (data not shown).…”

“…Whole genome sequencing (WGS) studies have been used to determine factors driving the emergence and transmission of Shigella spp. and have demonstrated that certain community outbreaks of shigellosis in the UK belonged to prolonged, global epidemics [5,[15][16][17][18]. These analysis have shown that lineages of S. flexneri serotypes 3a and 2a have exhibited intercontinental spread via sexual transmission in GBMSM networks, and subsequently acquired multiple antimicrobial resistance (AMR) determinants [5,17].…”

“…These analysis have shown that lineages of S. flexneri serotypes 3a and 2a have exhibited intercontinental spread via sexual transmission in GBMSM networks, and subsequently acquired multiple antimicrobial resistance (AMR) determinants [5,17]. Within the S. sonnei population, Baker et al (2018) [16] defined four clades associated with transmission in GBMSM communities, all within lineage III the dominant extant lineage both in the UK and globally [19,20]. A two-year population-level study of all cultured Shigella isolates in the state of Victoria, Australia (2016-2018) identified 2 predominant MSM lineages circulating [21]; the S. flexneri 2a lineage described above and an MDR S. sonnei clade associated with reduced susceptibility to azithromycin, trimethoprim-sulfamethoxazole and ciprofloxacin.…”