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PMID: 7962526 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Diminished virulence of a sar-/agr- mutant of Staphylococcus aureus in the rabbit model of endocarditis.

The Journal of clinical investigation ·Vol. 94 ·No. 5 ·1994-11-00 ·Pages 1815-22

Cheung AL, Eberhardt KJ, Chung E, Yeaman MR, Sullam PM, Ramos M, Bayer AS

Abstract

Microbial pathogenicity in Staphylococcus aureus is a complex process involving a number of virulence genes that are regulated by global regulatory systems including sar and agr. To evaluate the roles of these two loci in virulence, we constructed sar-/agr- mutants of strains RN6390 and RN450 and compared their phenotypic profiles to the corresponding single sar- and agr- mutants and parents. The secretion of all hemolysins was absent in the sar-/agr- mutants while residual beta-hemolysin activity remained in single agr- mutants. The fibronectin binding capacity was significantly diminished in both single sar- mutants and double mutants when compared with parents while the reduction in fibrinogen binding capacity in the double mutants was modest. In the rabbit endocarditis model, there was a significant decrease in both infectivity rates and intravegetation bacterial densities with the double mutant as compared to the parent (RN6390) at 10(3)-10(6) CFU inocula despite comparable levels of early bacteremia among various challenge groups. Notably, fewer bacteria in the double mutant group adhered to valvular vegetations at 30 min after challenge (10(6) CFU) than the parent group. These studies suggest that both the sar and agr loci are involved in initial valvular adherence, intravegetation persistence and multiplication of S. aureus in endocarditis.

Related Genes
agr sar
MeSH Terms
Animals Bacterial Adhesion Disease Models, Animal Endocarditis, Bacterial/microbiology Genes, Bacterial Mutation Phenotype Rabbits Staphylococcus aureus/genetics,pathogenicity Virulence
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Cheung A L
Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York 10021.
Eberhardt K J
Chung E
Yeaman M R
Sullam P M
Ramos M
Bayer A S
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI117530
Published
1994-11-00
Pages
1815-22
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC294579
Subset
IM
Grants
NIAID NIH HHS · AI-32506 · United States
NIAID NIH HHS · AI30061 · United States
External Links
PubMed source DOI: 10.1172/JCI117530 PMC Full Text View journal details
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