Remodeling of Staphylococcus epidermidis genome over three decades of nosocomial exposure

Staphylococcus epidermidis recently emerged as a major cause of medical device-associated infections. However, the role of the nosocomial environment in its evolution remains poorly understood. To investigate the genomic changes underlying S. epidermidis evolutionary history, we compared genomes of 1960s isolates, before its recognition as a human pathogen, to those from the 1990s, when it became prevalent in hospital-acquired infections. We found that S. epidermidis from the 1960s and 1990s shared similar population structures, with the A/C cluster predominating in both periods. Recombination was frequent, particularly in the A/C cluster, and occurred throughout the chromosome. Alterations in the mobile genetic elements of the 1990s isolates caused a drastic genomic change, characterized by phage loss, and staphylococcal cassette chromosome elements and insertion sequences acquisition. The 1990s isolates gained multiple antibiotic resistance and virulence genes, which are associated with biofilm formation and persistence. Genomic analysis of the orfX/rmlH vicinity revealed differences between the two groups of isolates. The 1960s isolates harbored a complex orfX/rmlH vicinity containing multiple SCC and pseudoSCC, and genes with high homology to SCCmecIV, while the 1990s isolates contained only SCCmec and ACME. Interestingly, one early isolate carried a disrupted mecA, within a pseudoSCCmecIV, suggesting it may represent a precursor to the contemporary SCCmecIV. Our results showed that prolonged exposure to the hospital environment drove S. epidermidis genomic remodeling, including the accumulation of genes linked to antibiotic resistance, enhanced colonization, biofilm formation, genome plasticity, and the loss of bacteriophages -contributing to its success as a persistent nosocomial pathogen.