The Staphylococcus aureus ArlRS Two-Component System Is a Novel Regulator of Agglutination and Pathogenesis

PLoS Pathogens

Jeffrey M. Boyd¹  Adam R. Spaulding²  Cheryl L. Malone²  Alexander R. Horswill²  Jennifer N. Walker²  Carolyn B. Rosenthal²  Wilmara Salgado-Pabón²  Heidi A. Crosby²  Patrick M. Schlievert² 

[1] Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, New Jersey, United States of America;Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America

关键词: Staphylococcus aureus;    Rabbits;    Endocarditis;    Pathogenesis;    Bacterial biofilms;    Phenotypes;    Polymerase chain reaction;    Fibrinogen;   

DOI  :  10.1371/journal.ppat.1003819

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY