title: Impact of sub-inhibitory antibiotics on fibronectin-mediated host cell adhesion and invasion by Staphylococcus aureus.
abstract: BACKGROUND
  Staphylococcus aureus is a well-armed pathogen prevalent in severe infections such as endocarditis and osteomyelitis. Fibronectin-binding proteins A and B, encoded by fnbA/B, are major pathogenesis determinants in these infections through their involvement in S. aureus adhesion to and invasion of host cells. Sub-minimum inhibitory concentrations (sub-MICs) of antibiotics, frequently occurring in vivo because of impaired drug diffusion at the infection site, can alter S. aureus phenotype. We therefore investigated their impact on S. aureus fibronectin-mediated adhesiveness and invasiveness.
  
  
  METHODS
  After in vitro challenge of S. aureus 8325-4 and clinical isolates with sub-MICs of major anti-staphylococcal agents, we explored fnbA/B transcription levels, bacterial adhesiveness to immobilised human fibronectin and human osteoblasts in culture, and bacterial invasion of human osteoblasts.
  
  
  RESULTS
  Oxacillin, moxifloxacin and linezolid led to the development of a hyper-adhesive phenotype in the fibronectin adhesion assay that was consistent with an increase in fnbA/B transcription. Conversely, rifampin treatment decreased fibronectin binding in all strains tested without affecting fnbA/B transcription. Gentamicin and vancomycin had no impact on fibronectin binding or fnbA/B transcription levels. Only oxacillin-treated S. aureus displayed a significantly increased adhesion to cultured osteoblasts, but its invasiveness did not differ from that of untreated controls.
  
  
  CONCLUSIONS
  Our findings demonstrate that several antibiotics at sub-MICs modulate fibronectin binding in S. aureus in a drug-specific fashion. However, hyper- and hypo- adhesive phenotypes observed in controlled in vitro conditions were not fully confirmed in whole cell infection assays. The relevance of adhesion modulation during in vivo infections is thus still uncertain and requires further investigations.
authors.affiliation: INSERM, U851, Lyon 69008, France.
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Rasigade
authors.forename: Abdelmalek
authors.initials: A
authors.lastname: Moulay
authors.forename: Yannick
authors.initials: Y
authors.lastname: Lhoste
authors.forename: Anne
authors.initials: A
authors.lastname: Tristan
authors.forename: Michele
authors.initials: M
authors.lastname: Bes
authors.forename: François
authors.initials: F
authors.lastname: Vandenesch
authors.forename: Jerome
authors.initials: J
authors.lastname: Etienne
authors.forename: Gerard
authors.initials: G
authors.lastname: Lina
authors.forename: Frederic
authors.initials: F
authors.lastname: Laurent
authors.forename: Oana
authors.initials: O
authors.lastname: Dumitrescu
mesh_terms: D018829:Adhesins, Bacterial / Q000187:drug effects* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects*; D005353:Fibronectins / Q000187:drug effects* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; D005353:Fibronectins; C078635:fibronectin-binding proteins, bacterial