Journal article
The Staphylococcus aureus ArlRS two-component system is a novel regulator of agglutination and pathogenesis
PLoS pathogens, Vol.9(12), pp.e1003819-17
2013
DOI: 10.1371/journal.ppat.1003819
PMCID: PMC3868527
PMID: 24367264
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.
Details
- Title: Subtitle
- The Staphylococcus aureus ArlRS two-component system is a novel regulator of agglutination and pathogenesis
- Creators
- Jennifer N Walker - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaHeidi A Crosby - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaAdam R Spaulding - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaWilmara Salgado-Pabón - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaCheryl L Malone - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaCarolyn B Rosenthal - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaPatrick M Schlievert - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaJeffrey M Boyd - Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, New Jersey, United States of AmericaAlexander R Horswill - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.9(12), pp.e1003819-17
- DOI
- 10.1371/journal.ppat.1003819
- PMID
- 24367264
- PMCID
- PMC3868527
- NLM abbreviation
- PLoS Pathog
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Publisher
- United States
- Grant note
- AI083211 / NIAID NIH HHS\r\nT32 AI007511 / NIAID NIH HHS\r\nT90 DE023520 / NIDCR NIH HHS\r\nAI157153 / NIAID NIH HHS
- Language
- English
- Date published
- 2013
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984001135402771
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