Wellcome Trust (grant number 098051).

Shigella flexneri is the most common cause of bacterial dysentery in low-income countries. Despite this, S. flexneri remains largely unexplored from a genomic standpoint and is still described using a vocabulary based on serotyping reactions developed over half-a-century ago. Here we combine whole genome sequencing with geographical and temporal data to examine the natural history of the species. Our analysis subdivides S. flexneri into seven phylogenetic groups (PGs); each containing two-or-more serotypes and characterised by distinct virulence gene complement and geographic range. Within the S. flexneri PGs we identify geographically restricted sub-lineages that appear to have persistently colonised regions for many decades to over 100 years. Although we found abundant evidence of antimicrobial resistance (AMR) determinant acquisition, our dataset shows no evidence of subsequent intercontinental spread of antimicrobial resistant strains. The pattern of colonisation and AMR gene acquisition suggest that S. flexneri has a distinct life-cycle involving local persistence.DOI: http://dx.doi.org/10.7554/eLife.07335.001

A new highly virulent clone of EHEC O26 has emerged in Europe. Its reservoirs and sources warrant identification.

Shiga-toxin-producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the emergence of this serotype in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains observed today. In this study, the genomes of over 1000 isolates from both human clinical cases and cattle, spanning the history of STEC O157:H7 in the UK, were sequenced. Phylogenetic analysis revealed the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimated the time to evolution of the most recent common ancestor of the current circulating global clone to be 175 years ago. This event was followed by rapid diversification. We show the acquisition of specific virulence determinates has occurred relatively recently and coincides with its recent detection in the human population. We used clinical outcome data from 493 cases of STEC O157:H7 to assess the relative risk of severe disease including haemolytic uraemic syndrome from each of the defined clades in the population and show the dramatic effect Shiga toxin repertoire has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years, one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. There is a need to understand the selection pressures maintaining Shiga-toxin-encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations.

WGS has come of age as a molecular typing tool to inform national surveillance of STEC O157; it can be used in real time to provide the highest strain-level resolution for outbreak investigation. WGS allows linked cases to be identified with unprecedented specificity and sensitivity that will facilitate targeted and appropriate public health investigations.

Horizontal gene transfer has played a role in developing the global public health crisis of antimicrobial resistance (AMR). However, the dynamics of AMR transfer through bacterial populations and its direct impact on human disease is poorly elucidated. Here, we study parallel epidemic emergences of multiple Shigella species, a priority AMR organism, in men who have sex with men to gain insight into AMR emergence and spread. Using genomic epidemiology, we show that repeated horizontal transfer of a single AMR plasmid among Shigella enhanced existing and facilitated new epidemics. These epidemic patterns contrasted with slighter, slower increases in disease caused by organisms with vertically inherited (chromosomally encoded) AMR. This demonstrates that horizontal transfer of AMR directly affects epidemiological outcomes of globally important AMR pathogens and highlights the need for integration of genomic analyses into all areas of AMR research, surveillance and management.

Between 1 January 2009 and 31 December 2012 in England, a total of 3717 cases were reported with evidence of Shiga toxin-producing E. coli (STEC) infection, and the crude incidence of STEC infection was 1·80/100 000 person-years. Incidence was highest in children aged 1-4 years (7·63/100 000 person-years). Females had a higher incidence of STEC than males [rate ratio (RR) 1·24, P < 0·001], and white ethnic groups had a higher incidence than non-white ethnic groups (RR 1·43, P < 0·001). Progression to haemolytic uraemic syndrome (HUS) was more frequent in females and children. Non-O157 STEC strains were associated with higher hospitalization and HUS rates than O157 STEC strains. In STEC O157 cases, phage type (PT) 21/28, predominantly indigenously acquired, was also associated with more severe disease than other PTs, as were strains encoding stx2 genes. Incidence of STEC was over four times higher in people residing in rural areas than urban areas (RR 4·39, P < 0·001). Exposure to livestock and/or their faeces was reported twice as often in cases living in rural areas than urban areas (P < 0·001). Environmental/animal contact remains an important risk factor for STEC transmission and is a significant driver in the burden of sporadic STEC infection. The most commonly detected STEC serogroup in England was O157. However, a bias in testing methods results in an unquantifiable under-ascertainment of non-O157 STEC infections. Implementation of PCR-based diagnostic methods designed to detect all STEC, to address this diagnostic deficit, is therefore important.

Objectives To inform control strategies undertaken as part of an outbreak of Shigella flexneri 3a among men who have sex with men (MSM). Methods All men aged ≥18 years diagnosed with S flexneri 3a between October 2012 and May 2013 were invited to participate. Semistructured in-depth quantitative interviews were conducted to explore lifestyle and sexual behaviour factors. Results Of 53 men diagnosed, 42 were interviewed of whom 34 were sexually active MSM. High numbers of sexual partners were reported (median=22) within the previous year; most were casual encounters met through social media networking sites (21/34). 63% (20/32) were HIV-positive and actively sought positive partners for condomless sex. 62% (21/34) of men had used chemsex drugs (mephedrone, crystal methamphetamine and γ-butyrolactone/γ-hydroxybutrate), which facilitate sexually disinhibiting behaviour during sexual encounters. 38% (8/21) reported injecting chemsex drugs. Where reported almost half (12/23) had attended or hosted sex parties. All reported oral-anal contact and fisting was common (16/34). Many had had gonorrhoea (23/34) and chlamydia (17/34). HIV-positive serostatus was associated with both insertive anal intercourse with a casual partner and receptive fisting (adjusted OR=15.0, p=0.01; adjusted OR=18.3, p=0.03) as was the use of web applications that promote and facilitate unprotected sex (adjusted OR=19.8, p=0.02). Conclusions HIV-positive MSM infected with S flexneri 3a used social media to meet sexual partners for unprotected sex mainly at sex parties. The potential for the transmission of S flexneri, HIV and other infections is clear. MSM need to be aware of the effect that chemsex drugs have on their health.