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The Staphylococcus aureus Global Regulator MgrA Modulates Clumping and Virulence by Controlling Surface Protein
Heidi A Crosby1, Patrick M Schlievert1, Joseph A Merriman1
1Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Plos Pathogens
|May 5, 2016
Summary
Staphylococcus aureus clumping and virulence are controlled by the ArlRS-MgrA regulatory pathway. This system represses surface proteins like Ebh, SraP, and SasG, impacting infection and biofilm formation.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Staphylococcus aureus is a significant human pathogen.
- S. aureus forms clumps in fibrinogen, aiding adhesion and protection.
- The ArlRS system previously linked to clumping by repressing Ebh.
Purpose of the Study:
- Investigate the regulatory mechanism controlling S. aureus clumping.
- Elucidate the role of ArlRS and identify downstream targets.
- Determine the impact on virulence and biofilm formation.
Main Methods:
- Genetic manipulation of S. aureus strains (mutants, overexpression).
- RNA-sequencing (RNA-seq) to analyze gene expression changes.
- Electrophoretic Mobility Shift Assay (EMSA) for direct DNA-protein interactions.
- In vivo rabbit model of endocarditis for virulence assessment.
Main Results:
- ArlRS activates MgrA, which then represses Ebh and other surface proteins.
- MgrA directly represses ebh and sraP gene expression.
- Deleting ebh, sraP, and sasG restores clumping in mgrA mutants.
- MgrA mutants show reduced virulence in endocarditis model.
- Increased biofilm formation in mgrA mutants linked to SasG upregulation.
Conclusions:
- ArlRS and MgrA form a regulatory cascade controlling S. aureus virulence.
- This pathway regulates expression of multiple surface proteins crucial for pathogenesis.
- Surface protein steric hindrance and altered biofilm contribute to virulence phenotypes.
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