ArticlePLoS pathogens2010
Membrane damage elicits an immunomodulatory program in Staphylococcus aureus.
Article in PLoS pathogens, 2010. 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, 44 citations in OpenAlex.
- Comprehensive Phenotypic and Genomic Study for Understanding the Variability in Susceptibility of Listeria monocytogenes to AMPs and Bacteriocins.Probiotics and antimicrobial proteins · 2026Article
- Heme in Bacterial Pathogenesis and as an Antimicrobial Target.Chemical reviews · 2025Review
- SilversolPharmaceutics · 2024Article
- Isolation and functional analysis of phage-displayed antibody fragments targeting the staphylococcal superantigen-like proteins.MicrobiologyOpen · 2023Article
- Analysis of the Presence of the Virulence and Regulation Genes fromInternational journal of environmental research and public health · 2023Article
- Zinc Deprivation as a Promising Approach for Combating Methicillin-ResistantPathogens (Basel, Switzerland) · 2021Article
- Haem toxicity provides a competitive advantage to the clinically relevantMicrobiology (Reading, England) · 2021Article
- Staquorsin: A NovelFrontiers in microbiology · 2021Article
- Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase.Frontiers in microbiology · 2021Article
- Castaneroxy A From the Leaves ofFrontiers in pharmacology · 2021Article
- Clostridioides difficile Senses and Hijacks Host Heme for Incorporation into an Oxidative Stress Defense System.Cell host & microbe · 2020Article
- A Small Membrane Stabilizing Protein Critical to the Pathogenicity of Staphylococcus aureus.Infection and immunity · 2020Article
- Article
- Joint Genomic and Proteomic Analysis Identifies Meta-Trait Characteristics of Virulent and Non-virulentFrontiers in cellular and infection microbiology · 2018Article
- Antibacterial photosensitization through activation of coproporphyrinogen oxidase.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Bacterial Nitric Oxide Synthase Is Required for the Staphylococcus aureus Response to Heme Stress.ACS infectious diseases · 2016Article
- The Quorum Sensing Inhibitor Hamamelitannin Increases Antibiotic Susceptibility of Staphylococcus aureus Biofilms by Affecting Peptidoglycan Biosynthesis and eDNA Release.Scientific reports · 2016Article
- Photoinactivation of Staphylococcus aureus using protoporphyrin IX: the role of haem-regulated transporter HrtA.Applied microbiology and biotechnology · 2016Article
- Rot is a key regulator of Staphylococcus aureus biofilm formation.Molecular microbiology · 2015Article
- Selective chemical inhibition of agr quorum sensing in Staphylococcus aureus promotes host defense with minimal impact on resistance.PLoS pathogens · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The Staphylococcus aureus HrtAB system is a hemin-regulated ABC transporter composed of an ATPase (HrtA) and a permease (HrtB) that protect S. aureus against hemin toxicity. S. aureus strains lacking hrtA exhibit liver-specific hyper-virulence and upon hemin exposure over-express and secrete immunomodulatory factors that interfere with neutrophil recruitment to the site of infection. It has been proposed that heme accumulation in strains lacking hrtAB is the signal which triggers S. aureus to elaborate this anti-neutrophil response. However, we report here that S. aureus strains expressing catalytically inactive HrtA do not elaborate the same secreted protein profile. This result indicates that the physical absence of HrtA is responsible for the increased expression of immunomodulatory factors, whereas deficiencies in the ATPase activity of HrtA do not contribute to this process. Furthermore, HrtB expression in strains lacking hrtA decreases membrane integrity consistent with dysregulated permease function. Based on these findings, we propose a model whereby hemin-mediated over-expression of HrtB in the absence of HrtA damages the staphylococcal membrane through pore formation. In turn, S. aureus senses this membrane damage, triggering the increased expression of immunomodulatory factors. In support of this model, wildtype S. aureus treated with anti-staphylococcal channel-forming peptides produce a secreted protein profile that mimics the effect of treating DeltahrtA with hemin. These results suggest that S. aureus senses membrane damage and elaborates a gene expression program that protects the organism from the innate immune response of the host.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.