title: Pathophysiological Mechanisms of Staphylococcus Non-aureus Bone and Joint Infection: Interspecies Homogeneity and Specific Behavior of S. pseudintermedius.
abstract: Implicated in more than 60% of bone and joint infections (BJIs), Staphylococci have a particular tropism for osteoarticular tissue and lead to difficult-to-treat clinical infections. To date, Staphylococcus aureus internalization in non-professional phagocytic cells (NPPCs) is a well-explored virulence mechanism involved in BJI chronicity. Conversely, the pathophysiological pathways associated with Staphylococcus non-aureus (SNA) BJIs have scarcely been studied despite their high prevalence. In this study, 15 reference strains from 15 different SNA species were compared in terms of (i) adhesion to human fibronectin based on adhesion microplate assays and (ii) internalization ability, intracellular persistence and cytotoxicity based on an in vitro infection model using human osteoblasts. Compared to S. aureus, S. pseudintermedius was the only species that significantly adhered to human fibronectin. This species was also associated with high (even superior to S. aureus) internalization ability, intracellular persistence and cytotoxicity. These findings were confirmed using a panel of 17 different S. pseudintermedius isolates. Additionally, S. pseudintermedius internalization by osteoblasts was completely abolished in β1 integrin-deficient murine osteoblasts. These results suggest the involvement of β1 integrin in the invasion process, although this mechanism was previously restricted to S. aureus. In summary, our results suggest that internalization into NPPCs is not a classical pathophysiologic mechanism of SNA BJIs. S. pseudintermedius appears to be an exception, and its ability to invade and subsequently induce cytotoxicity in NPPCs could explain its severe and necrotic forms of infection, notably in dogs, which exhibit a high prevalence of S. pseudintermedius infection.
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université de Lyon 1, ENS de Lyon, Team "Pathogenesis of staphylococcal infections"Lyon, France; Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de LyonLyon, France.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Maali
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université de Lyon 1, ENS de Lyon, Team "Pathogenesis of staphylococcal infections"Lyon, France; Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de LyonLyon, France.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Martins-Simões
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université de Lyon 1, ENS de Lyon, Team "Pathogenesis of staphylococcal infections"Lyon, France; Infectious Diseases Department, Northern Hospital Group, Hospices Civils de LyonLyon, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Valour
authors.affiliation: INSERM U1209, Albert Bonniot InstituteGrenoble, France; Université Grenoble AlpesGrenoble, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bouvard
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université de Lyon 1, ENS de Lyon, Team "Pathogenesis of staphylococcal infections"Lyon, France; National Reference Center of Staphylococci, Hospices Civils de LyonLyon, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Rasigade
authors.affiliation: National Reference Center of Staphylococci, Hospices Civils de Lyon Lyon, France.
authors.forename: Michele
authors.initials: M
authors.lastname: Bes
authors.affiliation: ANSES - French Agency for Food, Environmental and Occupational Health & Safety Lyon, France.
authors.forename: Marisa
authors.initials: M
authors.lastname: Haenni
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université de Lyon 1, ENS de Lyon, Team "Pathogenesis of staphylococcal infections"Lyon, France; Infectious Diseases Department, Northern Hospital Group, Hospices Civils de LyonLyon, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Ferry
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université de Lyon 1, ENS de Lyon, Team "Pathogenesis of staphylococcal infections"Lyon, France; Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de LyonLyon, France; National Reference Center of Staphylococci, Hospices Civils de LyonLyon, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Laurent
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Université de Lyon 1, ENS de Lyon, Team "Pathogenesis of staphylococcal infections"Lyon, France; Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de LyonLyon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Trouillet-Assant
keywords: Staphylococcus non-aureus; Staphylococcus pseudintermedius; bone and joint infection (BJI); fibronectin; integrin α5β1; invasion