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A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19 disease in the UK from November, 2020. We report a post-hoc analysis of the efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), against this variant.

Vancomycin-resistant Enterococcus faecium(VREfm) is a leading cause of healthcare-associated infection. Reservoirs of VREfm are largely assumed to be nosocomial although there is a paucity of data on alternative sources. Here, we describe an integrated epidemiological and genomic analysis of E. faeciumassociated with bloodstream infection and isolated from wastewater. Treated and untreated wastewater from 20 municipal treatment plants in the East of England, United Kingdom was obtained and cultured to isolate E. faecium, ampicillin-resistant E. faecium(AREfm), and VREfm. VREfm was isolated from all 20 treatment plants and was released into the environment by 17/20 plants, the exceptions using terminal ultraviolet light disinfection. Median log10counts of AREfm and VREfm in untreated wastewater from 10 plants in direct receipt of hospital sewage were significantly higher than 10 plants that were not. We sequenced and compared the genomes of 423 isolates from wastewater with 187 isolates associated with bloodstream infection at five hospitals in the East of England. Among 481 E. faeciumisolates belonging to the hospital-adapted clade, we observed genetic intermixing between wastewater and bloodstream infection, with highly related isolates shared between a major teaching hospital in the East of England and 9/20 plants. We detected 28 antibiotic resistance genes in the hospital-adapted clade, of which 23 were represented in bloodstream, hospital sewage, and municipal wastewater isolates. We conclude that our findings are consistent with widespread distribution of hospital-adapted VREfm beyond acute healthcare settings with extensive release of VREfm into the environment in the East of England.

The correct interpretation of microbial sequencing data applied to surveillance and outbreak investigation depends on accessible genomic databases to provide vital genetic context. Our aim was to construct and describe a United Kingdom MRSA database containing over 1000 methicillin-resistant Staphylococcus aureus(MRSA) genomes drawn from England, Northern Ireland, Wales, Scotland, and the Republic of Ireland over a decade. We sequenced 1013 MRSA submitted to the British Society for Antimicrobial Chemotherapy by 46 laboratories between 2001 and 2010. Each isolate was assigned to a regional healthcare referral network in England and was otherwise grouped based on country of origin. Phylogenetic reconstructions were used to contextualize MRSA outbreak investigations and to detect the spread of resistance. The majority of isolates (n= 783, 77%) belonged to CC22, which contains the dominant United Kingdom epidemic clone (EMRSA-15). There was marked geographic structuring of EMRSA-15, consistent with widespread dissemination prior to the sampling decade followed by local diversification. The addition of MRSA genomes from two outbreaks and one pseudo-outbreak demonstrated the certainty with which outbreaks could be confirmed or refuted. We identified local and regional differences in antibiotic resistance profiles, with examples of local expansion, as well as widespread circulation of mobile genetic elements across the bacterial population. We have generated a resource for the future surveillance and outbreak investigation of MRSA in the United Kingdom and Ireland and have shown the value of this during outbreak investigation and tracking of antimicrobial resistance.

Streptococcus pyogenesis a genetically diverse pathogen, with over 200 different genotypes defined by emmtyping, but only a minority of these genotypes are responsible for the majority of human infection in high-income countries. Two prevalent genotypes associated with disease rose to international dominance following recombination of a toxin locus that conferred increased expression. Here, we found that recombination of this locus and promoter has occurred in other diverse genotypes, events that may allow these genotypes to expand in the population. We identified an association between the loss of hyaluronic acid capsule synthesis and high toxin expression, which we propose may be associated with an adaptive advantage. As S. pyogenespathogenesis depends both on capsule and toxin production, new variants with altered expression may result in abrupt changes in the molecular epidemiology of this pathogen in the human population over time.

Genomic surveillance that combines bacterial sequencing and epidemiological information will become the gold standard for outbreak detection, but its clinical translation is hampered by the lack of automated interpretation tools. We performed a prospective pilot study to evaluate the analysis of methicillin-resistant Staphylococcus aureus(MRSA) genomes using the Next Gen Diagnostics (NGD) automated bioinformatics system.

There is growing evidence for the value of bacterial whole-genome sequencing in hospital outbreak investigations. Our aim was to develop methods that support efficient and accurate low-throughput clinical sequencing of methicillin-resistant Staphylococcus aureus(MRSA) isolates.

The increasing prevalence of E. colibloodstream infections is a serious public health problem. We used genomic epidemiology in a One Health study conducted in the East of England to examine putative sources of E. coliassociated with serious human disease. E. colifrom 1,517 patients with bloodstream infections were compared with 431 isolates from livestock farms and meat. Livestock-associated and bloodstream isolates were genetically distinct populations based on core genome and accessory genome analyses. Identical antimicrobial resistance genes were found in livestock and human isolates, but there was limited overlap in the mobile elements carrying these genes. Within the limitations of sampling, our findings do not support the idea that E. colicausing invasive disease or their resistance genes are commonly acquired from livestock in our region.

The rise in rates of human infection caused by vancomycin-resistant Enterococcus faecium(VREfm) strains between 1988 to the 2000s in Europe was suggested to be associated with acquisition from livestock. As a result, the European Union banned the use of the glycopeptide drug avoparcin as a growth promoter in livestock feed. While some studies reported a decrease in VREfm in livestock, others reported no reduction. Here, we report the first livestock VREfm prevalence survey in the UK since 2003 and the first large-scale study using whole-genome sequencing to investigate the relationship between E. faeciumstrains in livestock and humans. We found a low prevalence of VREfm in retail meat and limited evidence for recent sharing of strains between livestock and humans with bloodstream infection. There was evidence for limited sharing of genes encoding antibiotic resistance between these reservoirs, a finding which requires further research.

Longitudinal genomic and epidemiological surveillance of methicillin-resistant Staphylococcus aureusin the UK reveals extensive transmission in hospitals and the community.

ABSTRACTStaphylococcus argenteusis a newly named species previously described as a divergent lineage of Staphylococcus aureusthat has recently been shown to have a global distribution. Despite growing evidence of the clinical importance of this species, knowledge about its population epidemiology and genomic architecture is limited. We used whole-genome sequencing to evaluate and compare S. aureus(n= 251) and S. argenteus(n= 68) isolates from adults with staphylococcal sepsis at several hospitals in northeastern Thailand between 2006 and 2013. The majority (82%) of the S. argenteusisolates were of multilocus sequence type 2250 (ST2250). S. aureuswas more diverse, although 43% of the isolates belonged to ST121. Bayesian analysis suggested an S. argenteusST2250 substitution rate of 4.66 (95% confidence interval [CI], 3.12 to 6.38) mutations per genome per year, which was comparable to the S. aureusST121 substitution rate of 4.07 (95% CI, 2.61 to 5.55). S. argenteusST2250 emerged in Thailand an estimated 15 years ago, which contrasts with the S. aureusST1, ST88, and ST121 clades that emerged around 100 to 150 years ago. Comparison of S. argenteusST2250 genomes from Thailand and a global collection indicated a single introduction into Thailand, followed by transmission to local and more distant countries in Southeast Asia and further afield. S. argenteusand S. aureusshared around half of their core gene repertoire, indicating a high level of divergence and providing strong support for their classification as separate species. Several gene clusters were present in ST2250 isolates but absent from the other S. argenteusand S. aureusstudy isolates. These included multiple exotoxins and antibiotic resistance genes that have been linked previously with livestock-associated S. aureus, consistent with a livestock reservoir for S. argenteus. These genes appeared to be associated with plasmids and mobile genetic elements and may have contributed to the biological success of ST2250.IMPORTANCEIn this study, we used whole-genome sequencing to understand the genome evolution and population structure of a systematic collection of ST2250 S. argenteusisolates. A newly identified ancestral species of S. aureus, S. argenteushas become increasingly known as a clinically important species that has been reported recently across various countries. Our results indicate that S. argenteushas spread at a relatively rapid pace over the past 2 decades across northeastern Thailand and acquired multiple exotoxin and antibiotic resistance genes that have been linked previously with livestock-associated S. aureus. Our findings highlight the clinical importance and potential pathogenicity of S. argenteusas a recently emerging pathogen.