Completed genome and emergence scenario of the multidrug-resistant nosocomial opportunistic pathogen Staphylococcus epidermidis ST215

Abstract Background A multidrug-resistant genetic lineage of Staphylococcus epidermidis named ST215 causes prosthetic joint infections and other deep surgical site infections in Northern European residents. Increases in the rate and breadth of resistance among S. epidermidis strains are a concerning global trend. We used whole-genome sequencing to characterize ST215 in a healthcare setting. Results We used publicly available diverse S. epidermidis genomes with a global distribution as a reference and generated 11 short-read genomes of S. epidermidis ST215 from a university hospital in Sweden. One ST215 isolate genome was finished using long-reads, resulting in a circular 2,676,787 bp chromosome and a 2,326 bp plasmid. We generated 11 short-read genomes of ST2, which is another common multidrug-resistant genetic lineage at the same hospital and at multiple locations worldwide. Using genome data, we established genetic relationships between the ST215, ST2, and reference genomes. We investigated the function of recombination during evolution from a recent common ancestor of ST2 and ST215 and found signals of multiple recombination events with an average size of 30–50 kb. By comparing the results of antimicrobial susceptibility testing for 31 antimicrobial drugs with the genome content encoding antimicrobial resistance in the ST215 and ST2 isolates, we found highly similar phenotypical antimicrobial resistance traits between the isolates, with 22 resistance genes being shared between all the ST215 and ST2 genomes. The ST215 genome contained 29 genes that were historically identified as virulence genes of S. epidermidis ST2. We established that in the nucleotide sequence stretches identified as recombination events, virulence genes were overrepresented in ST215, while antibiotic resistance genes (ARGs) were overrepresented in ST2. Conclusions We found that the two phylogenetically distinct lineages, ST215 and ST2, of S. epidermidis have evolved similarly and acquired antibiotic resistance and virulence genes through recombination events. The ST215 lineage exemplifies the recent evolutionary emergence of a multidrug-resistant healthcare-associated pathogen, and there is a thin line between commensal bacteria and successful pathogens.