ArticleInfection and immunity2016
The GraS Sensor in Staphylococcus aureus Mediates Resistance to Host Defense Peptides Differing in Mechanisms of Action.
Article in Infection and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Differential pathogenic and commensal response ofJournal of bacteriology · 2026Article
- Virulence Phenotypes Differentiate Persistent vs. Resolving Isolates of HumanAntibiotics (Basel, Switzerland) · 2026Article
- Phage-Encoded Virulence Factor, Gp05, Alters Membrane Phospholipids and Reduces Antimicrobial Susceptibility in Methicillin-Resistant Staphylococcus aureus.The Journal of infectious diseases · 2025Article
- sRNA-mediated crosstalk between cell wall stress and galactose metabolism in Staphylococcus aureus.Nucleic acids research · 2025Article
- Uncovering the genetic basis ofiScience · 2025Article
- LiaR-dependent gene expression contributes to antimicrobial responses in group AAntimicrobial agents and chemotherapy · 2024Article
- The Archetypal Gamma-Core Motif of Antimicrobial Cys-Rich Peptides Inhibits HInternational journal of molecular sciences · 2024Article
- Guarding the walls: the multifaceted roles of Bce modules in cell envelope stress sensing and antimicrobial resistance.Journal of bacteriology · 2024Review
- Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Gp05, a Prophage-Encoded Virulence Factor, Contributes to Persistent Methicillin-Resistant Staphylococcus aureus Endovascular Infection.Microbiology spectrum · 2023Article
- Role of the Staphylococcus aureus Extracellular Loop of GraS in Resistance to Distinct Human Defense Peptides in PMN and Invasive Cardiovascular infections.Infection and immunity · 2021Article
- GraS Sensory Activity in Staphylococcus epidermidis Is Modulated by the "Guard Loop" of VraG and the ATPase Activity of VraF.Journal of bacteriology · 2021Article
- Antimicrobial Peptides with Antibacterial Activity against Vancomycin-ResistantInternational journal of molecular sciences · 2021Review
- Mechanistic Fingerprinting Reveals Kinetic Signatures of Resistance to Daptomycin and Host Defense Peptides inAntibiotics (Basel, Switzerland) · 2021Article
- GraXRS-Dependent Resistance of Staphylococcus aureus to Human Osteoarthritic Synovial Fluid.mSphere · 2021Article
- The extracellular loop of the membrane permease VraG interacts with GraS to sense cationic antimicrobial peptides in Staphylococcus aureus.PLoS pathogens · 2021Article
- PACAP is a pathogen-inducible resident antimicrobial neuropeptide affording rapid and contextual molecular host defense of the brain.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Novel Functions and Signaling Specificity for the GraS Sensor Kinase of Staphylococcus aureus in Response to Acidic pH.Journal of bacteriology · 2020Article
- Inhibiting the two-component system GraXRS with verteporfin to combat Staphylococcus aureus infections.Scientific reports · 2020Article
- Genetic Factors Associated with Increased Host Defense Antimicrobial Peptide Resistance in Sequence Type 5 Healthcare-Associated MRSA Clinical Isolates.Biomolecules · 2020Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Staphylococcus aureus uses the two-component regulatory system GraRS to sense and respond to host defense peptides (HDPs). However, the mechanistic impact of GraS or its extracellular sensing loop (EL) on HDP resistance is essentially unexplored. Strains with null mutations in the GraS holoprotein (ΔgraS) or its EL (ΔEL) were compared for mechanisms of resistance to HDPs of relevant immune sources: neutrophil α-defensin (human neutrophil peptide 1 [hNP-1]), cutaneous β-defensin (human β-defensin 2 [hBD-2]), or the platelet kinocidin congener RP-1. Actions studied by flow cytometry included energetics (ENR); membrane permeabilization (PRM); annexin V binding (ANX), and cell death protease activation (CDP). Assay conditions simulated bloodstream (pH 7.5) or phagolysosomal (pH 5.5) pH contexts. S. aureus strains were more susceptible to HDPs at pH 7.5 than at pH 5.5, and each HDP exerted a distinct effect signature. The impacts of ΔgraS and ΔΕL on HDP resistance were peptide and pH dependent. Both mutants exhibited defects in ANX response to hNP-1 or hBD-2 at pH 7.5, but only hNP-1 did so at pH 5.5. Both mutants exhibited hyper-PRM, -ANX, and -CDP responses to RP-1 at both pHs and hypo-ENR at pH 5.5. The actions correlated with ΔgraS or ΔΕL hypersusceptibility to hNP-1 or RP-1 (but not hBD-2) at pH 7.5 and to all study HDPs at pH 5.5. An exogenous EL mimic protected mutant strains from hNP-1 and hBD-2 but not RP-1, indicating that GraS and its EL play nonredundant roles in S. aureus survival responses to specific HDPs. These findings suggest that GraS mediates specific resistance countermeasures to HDPs in immune contexts that are highly relevant to S. aureus pathogenesis in humans.
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