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.
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.
Entenza
Jose-Manuel
JM
Department of Medical Microbiology, University of Zürich, Gloriastrasse 32, CH-8028 Zürich, Switzerland.
Moreillon
Philippe
P
Senn
Maria Magdalena
MM
Kormanec
Jan
J
Dunman
Paul M
PM
Berger-Bächi
Brigitte
B
Projan
Steven
S
Bischoff
Markus
M
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
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