title: The Staphylococcus aureus epidermal cell differentiation inhibitor toxin promotes formation of infection foci in a mouse model of bacteremia.
abstract: Inactivation of the host GTPase RhoA by staphylococcal epidermal cell differentiation inhibitor (EDIN) exotoxins triggers the formation of large transcellular tunnels, named macroapertures, in endothelial cells. We used bioluminescent strains of Staphylococcus aureus to monitor the formation of infection foci during the first 24 h of hematogenous bacterial dissemination. Clinically derived EDIN-expressing S. aureus strains S25 and Xen36 produced many disseminated foci. EDIN had no detectable impact on infection foci in terms of histopathology or the intensity of emitted light. Moreover, EDIN did not modify the course of bacterial clearance from the bloodstream. In contrast, we show that EDIN expression promotes a 5-fold increase in the number of infection foci produced by Xen36. This virulence activity of EDIN requires RhoA ADP-ribosyltranferase activity. These results suggest that EDIN is a risk factor for S. aureus dissemination through the vasculature by virtue of its ability to promote the formation of infection foci in deep-seated tissues.
authors.affiliation: INSERM, U895, C3M, Toxines Microbiennes dans la Relation Hôte Pathogènes, Université de Nice-Sophia-Antipolis, UFR Médecine, IFR50, Nice 06204, France. munro@unice.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Munro
authors.forename: Maxime
authors.initials: M
authors.lastname: Benchetrit
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Nahori
authors.forename: Caroline
authors.initials: C
authors.lastname: Stefani
authors.forename: René
authors.initials: R
authors.lastname: Clément
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Michiels
authors.forename: Luce
authors.initials: L
authors.lastname: Landraud
authors.forename: Olivier
authors.initials: O
authors.lastname: Dussurget
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lemichez
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000382:microbiology* / Q000473:pathology*; D001426:Bacterial Proteins / Q000633:toxicity*; D005260:Female; D017930:Genes, Reporter; D006651:Histocytochemistry; D006801:Humans; D008163:Luminescent Measurements; D051379:Mice; D008807:Mice, Inbred BALB C; D008853:Microscopy; D013211:Staphylococcus aureus / Q000302:isolation & purification / Q000472:pathogenicity*; D037521:Virulence Factors / Q000633:toxicity*; D051598:Whole Body Imaging; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; C067120:epidermal cell differentiation inhibitor, Staphylococcus aureus; D020742:rhoA GTP-Binding Protein