title: Increased virulence of a fibronectin-binding protein mutant of Staphylococcus aureus in a rat model of pneumonia.
abstract: Fibronectin-binding proteins mediate Staphylococcus aureus internalization into nonphagocytic cells in vitro. We have investigated whether fibronectin-binding proteins are virulence factors in the pathogenesis of pneumonia by using S. aureus strain 8325-4 and isogenic mutants in which fibronectin-binding proteins were either deleted (DU5883) or overexpressed [DU5883(pFnBPA4)]. We first demonstrated that fibronectin-binding proteins mediate S. aureus internalization into alveolar epithelial cells in vitro and that S. aureus internalization into alveolar epithelial cells requires actin rearrangement and protein kinase activity. Second, we established a rat model of S. aureus-induced pneumonia and measured lung injury and bacterial survival at 24 and 96 h postinoculation. S. aureus growth and the extent of lung injury were both increased in rats inoculated with the deletion mutant (DU5883) in comparison with rats inoculated with the wild-type (8325-4) and the fibronectin-binding protein-overexpressing strain DU5883(pFnBPA4) at 24 h postinfection. Morphological evaluation of infected lungs at the light and electron microscopic levels demonstrated that S. aureus was present within neutrophils from both 8325-4- and DU5883-inoculated lungs. Our data suggest that fibronectin-binding protein-mediated internalization into alveolar epithelial cells is not a virulence mechanism in a rat model of pneumonia. Instead, our data suggest that fibronectin-binding proteins decrease the virulence of S. aureus in pneumonia.
authors.affiliation: Rayne Laboratory, Respiratory Medicine, University of Edinburgh, Scotland. Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin, Ireland.
authors.forename: Mary C
authors.initials: MC
authors.lastname: McElroy
authors.forename: David J
authors.initials: DJ
authors.lastname: Cain
authors.forename: Christine
authors.initials: C
authors.lastname: Tyrrell
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Foster
authors.forename: Christopher
authors.initials: C
authors.lastname: Haslett
mesh_terms: D018829:Adhesins, Bacterial; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D015824:Blood-Air Barrier / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002461:Cell Line, Transformed; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D005353:Fibronectins / Q000276:immunology*; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D016296:Mutagenesis; D020556:Neutrophil Infiltration / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000097:blood / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D051381:Rats; D013203:Staphylococcal Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; D000952:Antigens, Polyomavirus Transforming; D001426:Bacterial Proteins; D002352:Carrier Proteins; D005353:Fibronectins; C078635:fibronectin-binding proteins, bacterial