F LAUMAY¹, AR CORVAGLIA¹, SM DIENE¹, N VAN DER MEE-MARQUET², P FRANCOIS<sup>1

1</sup>Genomic Research Lab, Department of Infectious Diseases Geneva University Hospital Rue Gabrielle-Perret-Gentil 4 CH-1211 GENEVA 14 SWITZERLAND, ²CHRU de Tours, Département de Microbiologie et Hygiène, Hôpital Trousseau, Réseau des Hygiénistes du Centre RHC, UMR 1282, Infectiologie Santé Publique, Université de Tours, 37044 TOURS cedex

Staphylococcus aureus is a ubiquitous bacterium, frequently colonizing human skin but also a highly pathogenic microorganism. Part of its virulence is related to the acquisition of mobile genetic elements (MGEs).Lysogenic bacteriophages are a type of MGEs known to play an important role in S. aureus pathogenicity. Recently, Uhlemann et al. (2012) described the emergence of S. aureus CC398 strains initially colonizing animals and now able to infect and spread in humans living in animal-free environments. We analysed 21 isolates of CC398 by whole genome sequencing, from cases of colonization and infections in animals and humans; it appears that their prophages content provides them important new features contributing to their genome plasticity and virulence. Indeed, human-adapted strains are resistant to transduction and are 4-fold more prone to invade non-phagocytic cells than the positive control. However, the exact molecular mechanisms are unknown. In order to investigate the role of prophages in genome plasticity and virulence of CC398 human-adapted strains, we have selected: [i] the human-adapted S1 strain, which possesses two prophages; [ii] the prophage-free and non-human-adapted strain S123; [iii] the strain S123sa2, derived from prophage-free S123 and transduced with prophages from S1. We noticed that S123sa2 has acquired some important features related to virulence, like adhesion to human extracellular matrix proteins ability; moreover, S123 and S123sa2 display different gene expression profiles. Interestingly, numerous open reading frames (ORFs) of S1 prophages encode for hypothetical protein with unknowm function. Therefore, we plan to perform deletions of prophages’ ORFs in S124sa2 and to examine phenotypic features related to genome plasticity or virulence of mutants, in parallel with RNA-seq experiments. Elucidating the molecular mechanisms triggered by prophages harboured represents an original field of research, poorly explored to date in our settings. Providing new insights related to acquisition of genetic material is a prerequisite to identify new targets and to understand epidemiological and virulence evolution.