title: Role of sigmaB in the expression of Staphylococcus aureus cell wall adhesins ClfA and FnbA and contribution to infectivity in a rat model of experimental endocarditis.
abstract: Isogenic Staphylococcus aureus strains with different capacities to produce sigma(B) activity were analyzed for their ability to attach to fibrinogen- or fibronectin-coated surfaces or platelet-fibrin clots and to cause endocarditis in rats. In comparison to the sigma(B)-deficient strain, BB255, which harbors an rsbU mutation, both rsbU-complemented and sigma(B)-overproducing derivatives exhibited at least five times greater attachment to fibrinogen- and fibronectin-coated surfaces and showed increased adherence to platelet-fibrin clots. No differences in adherence were seen between BB255 and a DeltarsbUVWsigB isogen. Northern blotting analyses revealed that transcription of clfA, encoding fibrinogen-binding protein clumping factor A, and fnbA, encoding fibronectin-binding protein A, were positively influenced by sigma(B). Sigma(B) overproduction resulted in a statistically significant increase in positive spleen cultures and enhanced bacterial densities in both the aortic vegetations and spleens at 16 h postinoculation. In contrast, at 72 h postinoculation, tissues infected with the sigma(B) overproducer had lower bacterial densities than did those infected with BB255. These results suggest that although sigma(B) appears to increase the adhesion of S. aureus to various host cell-matrix proteins in vitro, it has limited effect on pathogenesis in the rat endocarditis model. Sigma(B) appears to have a transient enhancing effect on bacterial density in the early stages of infection that is lost during progression.
authors.affiliation: Department of Medical Microbiology, University of Zürich, Gloriastrasse 32, CH-8028 Zürich, Switzerland.
authors.forename: Jose-Manuel
authors.initials: JM
authors.lastname: Entenza
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreillon
authors.forename: Maria Magdalena
authors.initials: MM
authors.lastname: Senn
authors.forename: Jan
authors.initials: J
authors.lastname: Kormanec
authors.forename: Paul M
authors.initials: PM
authors.lastname: Dunman
authors.forename: Brigitte
authors.initials: B
authors.lastname: Berger-Bächi
authors.forename: Steven
authors.initials: S
authors.lastname: Projan
authors.forename: Markus
authors.initials: M
authors.lastname: Bischoff
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002473:Cell Wall; D004697:Endocarditis, Bacterial / Q000378:metabolism* / Q000382:microbiology; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D012808:Sigma Factor / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D005353:Fibronectins; C079011:SigB protein, Bacteria; D012808:Sigma Factor; D000511:alpha-Macroglobulins; C078635:fibronectin-binding proteins, bacterial; D005340:Fibrinogen