ArticleJournal of immunology (Baltimore, Md. : 1950)2014
The extracellular adherence protein from Staphylococcus aureus inhibits the classical and lectin pathways of complement by blocking formation of the C3 proconvertase.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- The C-terminal domain of Staphylococcus aureus Efb recruits FHR-2 to C3b, synergistically inhibiting the terminal complement pathway.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
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- New advances in understanding inhibition of myeloperoxidase and neutrophil serine proteases by two families of staphylococcal innate immune evasion proteins.Archives of biochemistry and biophysics · 2024Review
- The complement system: A key player in the host response to infections.European journal of immunology · 2024Review
- Staphylococcal peroxidase inhibitor (SPIN): Residue-level investigation of the helical bundle domain.Archives of biochemistry and biophysics · 2024Article
- Determinants of bacterial survival and proliferation in blood.FEMS microbiology reviews · 2024Review
- Protein Disulfide Isomerase and Extracellular Adherence Protein Cooperatively Potentiate Staphylococcal Invasion into Endothelial Cells.Microbiology spectrum · 2023Article
- Microbial evasion of the complement system: a continuous and evolving story.Frontiers in immunology · 2023Review
- A genetic regulatory see-saw of biofilm and virulence in MRSA pathogenesis.Frontiers in microbiology · 2023Review
- In Silico Genome-Scale Analysis of Molecular Mechanisms Contributing to the Development of a Persistent Infection with Methicillin-ResistantInternational journal of molecular sciences · 2022Article
- The survival of epidemic and sporadic MRSA on human skin mimics is determined by both host and bacterial factors.Epidemiology and infection · 2022Article
- The Role of Staphylococcal Biofilm on the Surface of Implants in Orthopedic Infection.Microorganisms · 2022Review
- The Role of the Oral Immune System in Oropharyngeal Candidiasis-Facilitated Invasion and Dissemination ofFrontiers in oral health · 2022Review
- The EPICC Family of Anti-Inflammatory Peptides: Next Generation Peptides, Additional Mechanisms of Action, andFrontiers in immunology · 2022Review
- Pathogenicity and virulence ofVirulence · 2021Review
- Monoclonal Antibodies Targeting Surface-Exposed and Secreted Proteins from Staphylococci.Vaccines · 2021Review
- Complement Inactivation Strategy ofInternational journal of molecular sciences · 2021Article
- Complement Evasion by Lyme Disease Spirochetes.Trends in microbiology · 2020Review
- An Irreversible Inhibitor to Probe the Role ofACS chemical biology · 2020Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
The pathogenic bacterium Staphylococcus aureus actively evades many aspects of human innate immunity by expressing a series of small inhibitory proteins. A number of these proteins inhibit the complement system, which labels bacteria for phagocytosis and generates inflammatory chemoattractants. Although the majority of staphylococcal complement inhibitors act on the alternative pathway to block the amplification loop, only a few proteins act on the initial recognition cascades that constitute the classical pathway (CP) and lectin pathway (LP). We screened a collection of recombinant, secreted staphylococcal proteins to determine whether S. aureus produces other molecules that inhibit the CP and/or LP. Using this approach, we identified the extracellular adherence protein (Eap) as a potent, specific inhibitor of both the CP and LP. We found that Eap blocked CP/LP-dependent activation of C3, but not C4, and that Eap likewise inhibited deposition of C3b on the surface of S. aureus cells. In turn, this significantly diminished the extent of S. aureus opsonophagocytosis and killing by neutrophils. This combination of functional properties suggested that Eap acts specifically at the level of the CP/LP C3 convertase (C4b2a). Indeed, we demonstrated a direct, nanomolar-affinity interaction of Eap with C4b. Eap binding to C4b inhibited binding of both full-length C2 and its C2b fragment, which indicated that Eap disrupts formation of the CP/LP C3 proconvertase (C4b2). As a whole, our results demonstrate that S. aureus inhibits two initiation routes of complement by expression of the Eap protein, and thereby define a novel mechanism of immune evasion.
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Registered trials
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