title: High level methicillin resistance correlates with reduced Staphylococcus aureus endothelial cell damage.
abstract: There has been controversy about the intrinsic virulence of methicillin-resistant Staphylococcus aureus (MRSA) as compared to methicillin-susceptible S. aureus (MSSA). To address this discrepancy, the intrinsic virulence of 42 MRSA and 40 MSSA clinical isolates was assessed by testing endothelial cell (EC) damage, a surrogate marker for virulence in blood stream infections. Since these clinical isolates represent a heterogeneous group, well characterized S. aureus laboratory strains with SCCmec loss- and gain-of-function mutations were used in addition. The clinical MRSA isolates carrying typical hospital acquired SCCmec types (I, II or III) induced significantly less damage (47.8%) as compared to isolates with other SCCmec types (62.3%, p=0.03) and MSSA isolates (64.2%, p<0.01). There was a strong inverse correlation between high-level oxacillin resistance and low EC damage induction (R2=0.4464, p<0.001). High-level oxacillin resistant strains (MIC >32μ/ml) grew significantly slower as compared to isolates with low-level resistance (p=0.047). The level of EC damage positively correlated with α- and δ-toxin production (p<0.0001 and p<0.05, respectively) but not with β-toxin production. Invasive MRSA isolates (n=21, 56.3%) were significantly less cytotoxic as compared to invasive MSSA isolates (n=20, 68.0%, p<0.05). There was no difference between EC damage induced by superficial versus invasive isolates in either MRSA or MSSA strains. Our data suggest that the intrinsic virulence of MRSA is similar or even reduced as compared to MSSA strains but is linked to the level of methicillin resistance.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. Electronic address: kati.seidlspirig@usz.ch.
authors.forename: Kati
authors.initials: K
authors.lastname: Seidl
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Michèle
authors.initials: M
authors.lastname: Leemann
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Miguel
authors.initials: M
authors.lastname: Palheiros Marques
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Carole
authors.initials: C
authors.lastname: Rachmühl
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Nadja
authors.initials: N
authors.lastname: Leimer
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Andreoni
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Achermann
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Annelies S
authors.initials: AS
authors.lastname: Zinkernagel
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001427:Bacterial Toxins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002876:Chromosomes, Bacterial; D042783:Endothelial Cells / Q000382:microbiology* / Q000502:physiology*; D017353:Gene Deletion; D023061:Gene Order; D054884:Host-Pathogen Interactions; D006801:Humans; D020071:Interspersed Repetitive Sequences; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D010068:Oxacillin / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D010068:Oxacillin
keywords: Endothelial cell damage; Methicillin resistance; Staphylococcus aureus; Virulence