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.
Highlights
Shigella are the most common bacterial cause of moderate to severe diarrhoea in children under 5 years old in Asia and Africa[1]
To investigate an epidemic phase of Shigella transmission associated with MSM21,23, isolates of S. sonnei and S. flexneri 2a submitted to the Gastrointestinal Bacteria Reference Unit (GBRU) at Public Health England (PHE) were representatively subsampled, with a random sample of isolates from each year proportional to the total number of annual cases being taken from across 2008–2014 (Fig. 1)
This study reveals important information about the epidemiology of shigellosis in a high-income nation where shigellosis is frequently related to travel
Summary
Shigella are the most common bacterial cause of moderate to severe diarrhoea in children under 5 years old in Asia and Africa[1]. The Shigella Resistance Locus Multiple Drug Resistance Element (SRL-MDRE) encoding resistance to ampicillin, chloramphenicol and tetracycline has been found in widely geographically-distributed S. dysenteriae, S. flexneri and S. sonnei[7,8,15,17] In addition to these horizontally-acquired AMR determinants, chromosomal mutations in the Quinolone Resistance Determining Region (QRDR) (that confer resistance to ciprofloxacin, the recommended treatment for shigellosis)[18] have been reported in shigellae isolated from Asia, Latin America, and high-income nations[7,11,14,19]. By providing the context necessary for interpreting national surveillance patterns, we reveal important qualitative insights on the importation and domestic transmission of Shigella in the UK, as well as on the prevalence and mobility of AMR among these globally-important pathogens
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