PMID:24367264

Citation	Walker, JN, Crosby, HA, Spaulding, AR, Salgado-Pabón, W, Malone, CL, Rosenthal, CB, Schlievert, PM, Boyd, JM and Horswill, AR (2013) The Staphylococcus aureus ArlRS two-component system is a novel regulator of agglutination and pathogenesis. PLoS Pathog. 9:e1003819
Abstract	Staphylococcus aureus is a prominent bacterial pathogen that is known to agglutinate in the presence of human plasma to form stable clumps. There is increasing evidence that agglutination aids S. aureus pathogenesis, but the mechanisms of this process remain to be fully elucidated. To better define this process, we developed both tube based and flow cytometry methods to monitor clumping in the presence of extracellular matrix proteins. We discovered that the ArlRS two-component system regulates the agglutination mechanism during exposure to human plasma or fibrinogen. Using divergent S. aureus strains, we demonstrated that arlRS mutants are unable to agglutinate, and this phenotype can be complemented. We found that the ebh gene, encoding the Giant Staphylococcal Surface Protein (GSSP), was up-regulated in an arlRS mutant. By introducing an ebh complete deletion into an arlRS mutant, agglutination was restored. To assess whether GSSP is the primary effector, a constitutive promoter was inserted upstream of the ebh gene on the chromosome in a wildtype strain, which prevented clump formation and demonstrated that GSSP has a negative impact on the agglutination mechanism. Due to the parallels of agglutination with infective endocarditis development, we assessed the phenotype of an arlRS mutant in a rabbit combined model of sepsis and endocarditis. In this model the arlRS mutant displayed a large defect in vegetation formation and pathogenesis, and this phenotype was partially restored by removing GSSP. Altogether, we have discovered that the ArlRS system controls a novel mechanism through which S. aureus regulates agglutination and pathogenesis.
Links	PubMed PMC3868527 Online version:10.1371/journal.ppat.1003819
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:FIBA		GO:0043152: induction of bacterial agglutination	ECO:0000314:		P		Figure 2. Fg induced agglutination in all wild type strains of S. aureus.	complete CACAO 10014
HUMAN:FIBA	involved_in	GO:0043152: induction of bacterial agglutination	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:FIBB		GO:0043152: induction of bacterial agglutination	ECO:0000314:		P		Figure 2. Fg induced agglutination in all of wild type strains of S. aureus	complete CACAO 10016
HUMAN:FIBB	involved_in	GO:0043152: induction of bacterial agglutination	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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