ArticleInfection and immunity2012
The Staphylococcus aureus two-component regulatory system, GraRS, senses and confers resistance to selected cationic antimicrobial peptides.
Article in Infection and immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed.
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- In Silico Identification and Molecular Characterization ofAntibiotics (Basel, Switzerland) · 2025Article
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- Phage-Encoded Virulence Factor, Gp05, Alters Membrane Phospholipids and Reduces Antimicrobial Susceptibility in Methicillin-Resistant Staphylococcus aureus.The Journal of infectious diseases · 2025Article
- Enhanced resistance of metal sequestering agents by reconfiguration of the Staphylococcus aureus cell wall.npj antimicrobials and resistance · 2025Article
- Antimicrobial Peptide Signaling in Skin Diseases.JID innovations : skin science from molecules to population health · 2025Review
- HNP-1: From Structure to Application Thanks to Multifaceted Functions.Microorganisms · 2025Review
- Response of Paenibacillus polymyxa SC2 to the stress of polymyxin B and a key ABC transporter YwjA involved.Applied microbiology and biotechnology · 2024Article
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- Guarding the walls: the multifaceted roles of Bce modules in cell envelope stress sensing and antimicrobial resistance.Journal of bacteriology · 2024Review
- The two-component regulatory systems GraRS and SrrAB mediateApplied and environmental microbiology · 2024Article
- Discovery of an antivirulence compound that targets the Staphylococcus aureus SaeRS two-component system to inhibit toxic shock syndrome toxin-1 production.The Journal of biological chemistry · 2024Article
- Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides in the Modern Era: An Updated Review.Microorganisms · 2024Review
- Crosstalk involving two-component systems inJournal of bacteriology · 2024Review
- Impact of precursor-derived peracetic acid on post-weaning diarrhea, intestinal microbiota, and predicted microbial functional genes in weaned pigs.Frontiers in microbiology · 2024Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
The two-component regulatory system, GraRS, appears to be involved in staphylococcal responses to cationic antimicrobial peptides (CAPs). However, the mechanism(s) by which GraRS is induced, regulated, and modulated remain undefined. In this study, we used two well-characterized MRSA strains (Mu50 and COL) and their respective mutants of graR and vraG (encoding the ABC transporter-dependent efflux pump immediately downstream of graRS), and show that (i) the expression of two key determinants of net positive surface charge (mprF and dlt) is dependent on the cotranscription of both graR and vraG, (ii) reduced expression of mprF and dlt in graR mutants was phenotypically associated with reduced surface-positive charge, (iii) this net reduction in surface-positive charge in graR and vraG mutants, in turn, correlated with enhanced killing by a range of CAPs of diverse structure and origin, including those from mammalian platelets (tPMPs) and neutrophils (hNP-1) and from bacteria (polymyxin B), and (iv) the synthesis and translocation of membrane lysyl-phosphatidylglycerol (an mprF-dependent function) was substantially lower in graR and vraG mutants than in parental strains. Importantly, the inducibility of mprF and dlt transcription via the graRS-vraFG pathway was selective, with induction by sublethal exposure to the CAPs, RP-1 (platelets), and polymyxin B, but not by other cationic molecules (hNP-1, vancomycin, gentamicin, or calcium-daptomycin). Although graR regulates expression of vraG, the expression of graR was codependent on an intact downstream vraG locus. Collectively, these data support an important role of the graRS and vraFG loci in the sensing of and response to specific CAPs involved in innate host defenses.
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