Staphylococcus epidermidis Phages Transduce Antimicrobial Resistance Plasmids and Mobilize Chromosomal Islands

Abstract

Staphylococcus epidermidis 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 Staphylococcus aureus, S. epidermidis 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 S. epidermidis phage typing, and the newly isolated phage E72, from a clinical S. epidermidis strain. The phages, classified in the family Siphoviridae and genus Phietavirus, exhibited an S. epidermidis-specific host range, and together they infected 49% of the 35 strains tested. A whole-genome comparison revealed evolutionary relatedness to transducing S. aureus phietaviruses. In accordance with this, all the tested phages were capable of transduction with high frequencies up to 10−4 among S. epidermidis 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 S. epidermidis. Similarly to S. aureus 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 S. epidermidis temperate phages in the evolution of S. epidermidis strains by horizontal gene transfer, which can also be utilized for S. epidermidis genetic studies. IMPORTANCE Multidrug-resistant strains of S. epidermidis 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 S. epidermidis phages. The high transduction frequencies of antimicrobial resistance plasmids and the first evidence of chromosomal island transfer emphasize the decisive role of S. epidermidis phages in attaining a higher pathogenic potential of host strains. To date, such importance has been attributed only to S. aureus phages, not to those of coagulase-negative staphylococci. This study also proved that the described transducing bacteriophages represent valuable genetic modification tools in S. epidermidis strains where other methods for gene transfer fail.

Growth-Dependent Predation and Generalized Transduction of Antimicrobial Resistance by Bacteriophage

“…We also show that transduction is the dominant mechanism to create new DRP throughout the experiment rather than growth of existing DRP. This echoes the conclusions of previously published work on the importance of transduction, including in vivo experiments and with other Staphylococcus species ( 4 , 5 , 29 , 54 ).…”

The bacterial capsule is a gatekeeper for mobile DNA

“…Most of the works on MGE focus on the isolated effects of plasmids, phages, or other MGE. However, it is becoming increasingly evident that different types of MGE operate simultaneously and even coordinately sometimes [9][10][11], and new studies will help to gain a better understanding how MGE interactions affect bacterial evolution. Finally, this study also emphasizes the impact of the host range of different MGE on their potential effects on bacterial evolution.…”

Staphylococcus ratti sp. nov. Isolated from a Lab Rat

“…For sequencing using the Oxford Nanopore platform, bacterial DNA was isolated as described previously [71]. The library was prepared using the SQK-RBK004 rapid barcoding kit (Oxford Nanopore Technologies, Oxford, UK) according to the manufacturer's instructions.…”