title: Genomics and epidemiology of Streptococcus pyogenes and Streptocossuc canis infections in Scotland
Creators: name: Pagnossin, Davide
Publisher: name: University of Glasgow
Year: 2023

description: Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is a strict human pathogen associated with a high burden of disease and millions of deaths per year worldwide. Although asymptomatic carriage and superficial infections are the most common outcomes of GAS colonisation of the human body, invasive infections and post-infectious complications are severe and not rare manifestations of GAS disease. Streptococcus canis, conversely, is an opportunistic pathogen that can colonise and cause disease in several mammalian species, particularly dogs and cats. Although rare, S. canis infections in humans can lead to death and are likely associated with zoonotic transfer from companion animals. Both S. pyogenes and S. canis are classified as pyogenic streptococci based on the clinical manifestations of infection and phylogenetic relatedness. The overarching aim of this work was to apply a multi-disciplinary approach to characterise the epidemiology of S. pyogenes and S. canis infections in humans and animals in Scotland. This was achieved through specific objectives: i) Characterisation of the main epidemiological features of invasive GAS (iGAS) infections in Scotland from 2014 to 2021. Findings confirmed that the annual incidence of iGAS disease in Scotland was comparable to the one reported in recent years in high-income countries. A seasonal pattern characterised by an increased incidence in Winter and Spring compared with Summer and Autumn was highlighted. Neonates, the elderly and people in their 30s were the age groups with the highest incidence of iGAS infections. Many S. pyogenes genotypes, defined as emm types, were implicated in invasive disease in recent years; some appeared to be consistently common throughout the study period, others were associated with temporary upsurges of disease or sporadic cases. The transition from the first to the second year of COVID-19 pandemic was characterised by a higher-than-expected emm type turnaround, suggesting that the restrictions in place had a repercussion on the circulation of specific strains of GAS in Scotland. ii) Investigation of an upsurge of iGAS disease associated with the genotype emm5.23 using whole genome sequencing (WGS) and transcriptomic analyses. Results of phylogenetic, virulence and AMR analyses suggested that acquisition of determinants responsible for a high-virulence phenotype in the emm5.23 population circulating in Scotland is unlikely. However, epidemiological connection of the cases appears possible making the emm5.23 infection upsurge a potentially undetected outbreak. iii) Characterisation of antimicrobial resistance (AMR), virulence characteristics and population structure of S. canis isolates from different species and geographic locations, including Scotland, using WGS analysis. Findings indicated that around 20% of S. canis strains (9/39) carried known AMR genes and were resistant to at least one antibiotic class, particularly tetracyclines, macrolides and lincosamides. The majority of virulence genes (17/19) detected in S. canis isolates were homologous to S. pyogenes genes, suggesting these two bacterial species might share similar virulence mechanisms. Genomic analyses of S. canis population structure did not show signs of host adaptation, indicating similar strains circulate and cause disease in different host species. The two genotyping systems currently used to classify S. canis strains, multi-locus sequence typing (MLST) and an S. canis M-like (SCM) typing scheme, have comparable accuracy in assigning genotypes but lack the discriminatory power of WGS to aid fine resolution such as that needed for outbreak settings. iv) Exploring and optimising the use of data visualisation to communicate the epidemiology of iGAS disease to a cohort of public health and laboratory workers in Scotland. A targeted survey with proposed multiple visualisations of reported results allowed to identify guiding principles that can facilitate the generation of data visualisations to communicate the epidemiology of iGAS disease to a specialised audience.