ArticleInfection and immunity2014
Site-specific mutation of the sensor kinase GraS in Staphylococcus aureus alters the adaptive response to distinct cationic antimicrobial peptides.
Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
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- Response of Paenibacillus polymyxa SC2 to the stress of polymyxin B and a key ABC transporter YwjA involved.Applied microbiology and biotechnology · 2024Article
- Guarding the walls: the multifaceted roles of Bce modules in cell envelope stress sensing and antimicrobial resistance.Journal of bacteriology · 2024Review
- Crosstalk involving two-component systems inJournal of bacteriology · 2024Review
- Antimicrobial Peptides and Small Molecules Targeting the Cell Membrane of Staphylococcus aureus.Microbiology and molecular biology reviews : MMBR · 2023Review
- Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria.Microorganisms · 2022Review
- Human serum triggers antibiotic tolerance in Staphylococcus aureus.Nature communications · 2022Article
- Article
- Two-Component Systems ofGenes · 2021Review
- Evaluation of small molecule kinase inhibitors as novel antimicrobial and antibiofilm agents.Chemical biology & drug design · 2021Review
- 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
- The extracellular loop of the membrane permease VraG interacts with GraS to sense cationic antimicrobial peptides in Staphylococcus aureus.PLoS pathogens · 2021Article
- The Role ofFrontiers in microbiology · 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
- Mechanisms of bactericidal action and resistance of polymyxins for Gram-positive bacteria.Applied microbiology and biotechnology · 2020Review
- Discovery of an antivirulence compound that reverses β-lactam resistance in MRSA.Nature chemical biology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The Staphylococcus aureus two-component regulatory system, GraRS, is involved in resistance to killing by distinct host defense cationic antimicrobial peptides (HD-CAPs). It is believed to regulate downstream target genes such as mprF and dltABCD to modify the S. aureus surface charge. However, the detailed mechanism(s) by which the histidine kinase, GraS, senses specific HD-CAPs is not well defined. Here, we studied a well-characterized clinical methicillin-resistant S. aureus (MRSA) strain (MW2), its isogenic graS deletion mutant (ΔgraS strain), a nonameric extracellular loop mutant (ΔEL strain), and four residue-specific ΔEL mutants (D37A, P39A, P39S, and D35G D37G D41G strains). The ΔgraS and ΔEL strains were unable to induce mprF and dltA expression and, in turn, demonstrated significantly increased susceptibilities to daptomycin, polymyxin B, and two prototypical HD-CAPs (hNP-1 and RP-1). Further, P39A, P39S, and D35G-D37G-D41G ΔEL mutations correlated with moderate increases in HD-CAP susceptibility. Reductions of mprF and dltA induction by PMB were also found in the ΔEL mutants, suggesting these residues are pivotal to appropriate activation of the GraS sensor kinase. Importantly, a synthetic exogenous soluble EL mimic of GraS protected the parental MW2 strain against hNP-1- and RP-1-mediated killing, suggesting a direct interaction of the EL with HD-CAPs in GraS activation. In vivo, the ΔgraS and ΔEL strains displayed dramatic reductions in achieved target tissue MRSA counts in an endocarditis model. Taken together, our results provide new insights into potential roles of GraS in S. aureus sensing of HD-CAPs to induce adaptive survival responses to these molecules.
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