Staphylococcus epidermidis Phages Transduce Antimicrobial Resistance Plasmids and Mobilize Chromosomal Islands

Abstract

<i>Staphylococcus epidermidis</i> is a leading opportunistic pathogen causing nosocomial infections that is notable for its ability to form a biofilm and for its high rates of antibiotic resistance. It serves as a reservoir of multiple antimicrobial resistance genes that spread among the staphylococcal population by horizontal gene transfer such as transduction. While phage-mediated transduction is well studied in <i>Staphylococcus aureus</i>, <i>S. epidermidis</i> transducing phages have not been described in detail yet. Here, we report the characteristics of four phages, 27, 48, 456, and 459, previously used for <i>S. epidermidis</i> phage typing, and the newly isolated phage E72, from a clinical <i>S. epidermidis</i> strain. The phages, classified in the family <i>Siphoviridae</i> and genus <i>Phietavirus</i>, exhibited an <i>S. epidermidis</i>-specific host range, and together they infected 49% of the 35 strains tested. A whole-genome comparison revealed evolutionary relatedness to transducing <i>S. aureus</i> phietaviruses. In accordance with this, all the tested phages were capable of transduction with high frequencies up to 10^-4 among <i>S. epidermidis</i> strains from different clonal complexes. Plasmids with sizes from 4 to 19 kb encoding resistance to streptomycin, tetracycline, and chloramphenicol were transferred. We provide here the first evidence of a phage-inducible chromosomal island transfer in <i>S. epidermidis</i> Similarly to <i>S. aureus</i> pathogenicity islands, the transfer was accompanied by phage capsid remodeling; however, the interfering protein encoded by the island was distinct. Our findings underline the role of <i>S. epidermidis</i> temperate phages in the evolution of <i>S. epidermidis</i> strains by horizontal gene transfer, which can also be utilized for <i>S. epidermidis</i> genetic studies.<b>IMPORTANCE</b> Multidrug-resistant strains of <i>S. epidermidis</i> emerge in both nosocomial and livestock environments as the most important pathogens among coagulase-negative staphylococcal species. The study of transduction by phages is essential to understanding how virulence and antimicrobial resistance genes spread in originally commensal bacterial populations. In this work, we provide a detailed description of transducing <i>S. epidermidis</i> phages. The high transduction frequencies of antimicrobial resistance plasmids and the first evidence of chromosomal island transfer emphasize the decisive role of <i>S. epidermidis</i> phages in attaining a higher pathogenic potential of host strains. To date, such importance has been attributed only to <i>S. aureus</i> phages, not to those of coagulase-negative staphylococci. This study also proved that the described transducing bacteriophages represent valuable genetic modification tools in <i>S. epidermidis</i> strains where other methods for gene transfer fail.