Abstract
Staphylococcus aureus is a major pathogen of humans and animals. The capacity of S. aureus to adapt to different host species and tissue types is strongly influenced by the acquisition of mobile genetic elements encoding determinants involved in niche adaptation. The genomic islands nSaa and nSab are found in almost all S. aureus strains and are characterized by extensive variation in virulence gene content. However the basis for the diversity and the mechanism underlying mobilization of the genomic islands between strains are unexplained. Here, we demonstrated that the genomic island, nSab, encoding an array of virulence factors including staphylococcal superantigens, proteases, and leukotoxins, in addition to bacteriocins, was transferrable in vitro to human and animal strains of multiple S. aureus clones via a resident prophage. The transfer of the nSab appears to have been accomplished by multiple conversions of transducing phage particles carrying overlapping segments of the nSab. Our findings solve a long-standing mystery regarding the diversification and spread of the genomic island nSab, highlighting the central role of bacteriophages in the pathogenic evolution of S. aureus.