bioRxiv2024
Staphylococcus pseudintermedius is the foremost cause of opportunistic canine skin and mucosal infections worldwide. Multidrug resistant (MDR) and methicillin-resistant S. pseudintermedius (MRSP) lineages have disseminated globally in the last decade and present significant treatment challenges. However, little is known regarding the factors that contribute to the success of MDR lineages. In this study, we compared the genome sequence of 110 UK isolates of S. pseudintermedius to 2,166 genomes of S. pseudintermedius populations from different continents. A novel core genome multi-locus typing scheme was generated to allow large scale, rapid and detailed analysis of S. pseudintermedius phylogenies, and was used to show that the S. pseudintermedius population structure is broadly segregated into an MDR population and a non-MDR population. MRSP lineages are predicted to either encode certain resistance genes chromosomally, or on plasmids, and this is associated with their MLST sequence type. Comparison of lineages most frequently implicated in disease, ST-45 and ST-71, with the phylogenetically related ST-496 lineage that has a comparatively low disease rate, revealed that ST-45 and ST-71 genomes encode distinct combinations of phage-defence systems and concurrently encode a high number of intact prophages. In contrast, ST-496 genomes encode a wider array of phage defence systems and lack intact, complete prophages. Additionally, we show that distinct prophages are widespread in S. pseudintermedius and appear to account for the vast majority of genomic diversity. These findings indicate that MRSP lineages have significant structural genomic differences, and that prophage integration, and differential antiviral systems correlate with the emergence of successful genotypes. Impact StatementStaphylococcus pseudintermedius is a major cause of soft tissue infections in dogs but may occasionally infect other companion animals and humans, most often veterinary professionals in primary care. Methicillin-resistant Staphylococcus pseudintermedius (MRSP) have emerged worldwide and are often linked to resistance to multiple antimicrobials, resulting in a significant health burden. Here, we analysed a large collection of S. pseudintermedius genome sequences, which has allowed a detailed characterisation of the molecular epidemiology and diversity of the species using a novel typing scheme. Here we show that closely related MRSP lineages differ in whether specific antibiotic resistance genes are encoded on potentially mobilisable plasmids, or more stably on the chromosome, indicating differing evolutionary trajectories of MRSP lineages. Comparison of the S. pseudintermedius types most frequently implicated in clinical cases to those associated with commensal carriage, showed that known genes thought to contribute to disease are universal, and therefore, not associated with the high incidence rates of disease of particular lineages. We demonstrate that MRSP sequence types linked to high disease rates lack specific phage-defence systems and are associated with a high burden of prophages. Data statementAll supporting data, code and protocols have been provided either within the article, through supplementary data files, or via Figshare and Zenodo. Six supplementary figures and one supplementary file are available with the online version of this article. Data summaryAll genome sequencing data (sequencing reads and genome assemblies) are available at the Sequence Read Archive (SRA) and Genomes repositories at NCBI, in Bioproject number PRJNA1153484. The information for the individual S. pseudintermedius genomes has been included in Supplementary File 1. Genome assemblies used in this study are available from https://zenodo.org/records/13692319, DOI 10.5281/zenodo.13692318. The S. pseudintermedius cgMLST scheme developed for this study has been made available via Zenodo (https://zenodo.org/records/13633136, DOI: 10.5281/zenodo.13633135) and Figshare (https://doi.org/10.6084/m9.figshare.26911654.v1, DOI: 10.6084/m9.figshare.26911654).