title: Adaptive processes of Staphylococcus aureus isolates during the progression from acute to chronic bone and joint infections in patients.
abstract: Staphylococcus aureus bone and joint infection (BJI) is associated with significant rates of chronicity and relapse. In this study, we investigated how S. aureus is able to adapt to the human environment by comparing isolates from single patients with persisting or relapsing BJIs that were recovered during the initial and recurrent BJI episodes. In vitro and in vivo assays and whole-genome sequencing analyses revealed that the recurrent isolates induced a reduced inflammatory response, formed more biofilms, persisted longer in the intracellular compartments of host bone cells, were less cytotoxic and induced less mortality in a mouse infection model compared with the initial isolates despite the lack of significant changes at the genomic level. These findings suggest that S. aureus BJI chronicization is associated with an in vivo bacterial phenotypical adaptation that leads to decreased virulence and host immune escape, which is linked to increased intraosteoblastic persistence and biofilm formation.
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Lyon, France. sophie.assant@chu-lyon.fr.|Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de Lyon, Lyon, France. sophie.assant@chu-lyon.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Trouillet-Assant
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Lyon, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Lelièvre
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Lyon, France.|Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de Lyon, Lyon, France.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Martins-Simões
authors.affiliation: Bioinformatics Laboratory - LABINFO, National Laboratory of Scientific Computation - LNCC/MCTI, Petrópolis, Brazil.
authors.forename: Luiz
authors.initials: L
authors.lastname: Gonzaga
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Lyon, France.|Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de Lyon, Lyon, France.
authors.forename: Jason
authors.initials: J
authors.lastname: Tasse
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Lyon, France.|Infectious Diseases Department, Northern Hospital Group, Hospices Civils de Lyon, Lyon, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Valour
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Lyon, France.|Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de Lyon, Lyon, France.|National Reference Center for Staphylococci, Hospices Civils de Lyon, Lyon, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Rasigade
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Lyon, France.|Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de Lyon, Lyon, France.|National Reference Center for Staphylococci, Hospices Civils de Lyon, Lyon, France.
authors.forename: François
authors.initials: F
authors.lastname: Vandenesch
authors.affiliation: Bioinformatics Laboratory - LABINFO, National Laboratory of Scientific Computation - LNCC/MCTI, Petrópolis, Brazil.
authors.forename: Rafael Lucas
authors.initials: RL
authors.lastname: Muniz Guedes
authors.affiliation: Bioinformatics Laboratory - LABINFO, National Laboratory of Scientific Computation - LNCC/MCTI, Petrópolis, Brazil.
authors.forename: Ana Tereza
authors.initials: AT
authors.lastname: Ribeiro de Vasconcelos
authors.affiliation: University of Nantes, Medical School, UPRES EA, 3826, Nantes, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Caillon
authors.affiliation: Orthopedic Surgery Department, Northern Hospital Group, Hospices Civils de Lyon, Lyon, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Lustig
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Lyon, France.|Infectious Diseases Department, Northern Hospital Group, Hospices Civils de Lyon, Lyon, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Ferry
authors.affiliation: University of Nantes, Medical School, UPRES EA, 3826, Nantes, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Jacqueline
authors.affiliation: Bioinformatics Laboratory - LABINFO, National Laboratory of Scientific Computation - LNCC/MCTI, Petrópolis, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Loss de Morais
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Lyon, France.|Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de Lyon, Lyon, France.|National Reference Center for Staphylococci, Hospices Civils de Lyon, Lyon, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Laurent
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001170:Arthritis, Infectious / Q000382:microbiology*; D018441:Biofilms; D002478:Cells, Cultured; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D006460:Hemolysin Proteins / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000276:immunology / Q000382:microbiology; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000502:physiology*
chemical_list: D006460:Hemolysin Proteins