K SEIDL¹, M LEEMAN¹, M MALHEIROS MARQUES¹, C RACHMÜHL¹, N LEIMER¹, F ANDREONI¹, Y ACHERMANN¹, AS ZINKERNAGEL<sup>1

1</sup>Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of nosocomial infections worldwide and has emerged as a community-associated pathogen. While numerous clinical studies suggest that MRSA are more virulent than methicillin-susceptible S. aureus (MSSA) several laboratory studies suggest the opposite. To address this discrepancy, we assessed the intrinsic virulence of 42 MRSA and 40 MSSA strains by testing endothelial cell (EC) damage, a surrogate marker for virulence in blood stream infections. More endothelial cell (EC) damage was induced by MSSA vs. MRSA isolates without reaching statistical significance (64.2 vs. 57.8%, p = 0.12). Invasive MSSA strains induced significantly more EC damage vs. invasive MRSA strains (p = 0.0147). MRSA isolates with high level oxacillin resistance (>32µg/ml) induced significantly less damage than isolates with relatively low level oxacillin resistance (MIC ≤ 32µg/ml, p < 0.0001). The level of oxacillin resistance negatively correlated with the ability to induce EC damage (R2 = 0.4464, p < 0.001). SCCmec excision in MRSA strains of different SCCmec types and different resistance levels had no significant effect on EC damage despite complete abolishment of oxacillin resistance suggesting that SCCmec itself has no impact on EC damage. Together, our findings suggest that worse clinical outcomes associated with MRSA are not due to a higher intrinsic virulence but due to other factors such as ineffective initial antimicrobial treatment or prognostic factors confounding with MRSA infections.