Attenuation of Staphylococcus aureus-Induced Bacteremia by Human Mini-Antibodies Targeting the Complement Inhibitory Protein Efb

The Journal of Immunology : Official Journal of the American Association of Immunologists
Maria Georgoutsou-SpyridonosGeorgia Sfyroera

Abstract

Staphylococcus aureus can cause a broad range of potentially fatal inflammatory complications (e.g., sepsis and endocarditis). Its emerging antibiotic resistance and formidable immune evasion arsenal have emphasized the need for more effective antimicrobial approaches. Complement is an innate immune sensor that rapidly responds to bacterial infection eliciting C3-mediated opsonophagocytic and immunomodulatory responses. Extracellular fibrinogen-binding protein (Efb) is a key immune evasion protein of S. aureus that intercepts complement at the level of C3. To date, Efb has not been explored as a target for mAb-based antimicrobial therapeutics. In this study, we have isolated donor-derived anti-Efb IgGs that attenuate S. aureus survival through enhanced neutrophil killing. A phage library screen yielded mini-Abs that selectively inhibit the interaction of Efb with C3 partly by disrupting contacts essential for complex formation. Surface plasmon resonance-based kinetic analysis enabled the selection of mini-Abs with favorable Efb-binding profiles as therapeutic leads. Mini-Ab-mediated blockade of Efb attenuated S. aureus survival in a whole blood model of bacteremia. This neutralizing effect was associated with enhanced neutrophi...Continue Reading

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Citations

Jun 21, 2016·Seminars in Immunology·Daniel Ricklin, John D Lambris
Jul 6, 2020·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Emily M EichenbergerBrinda C Prasad
Jun 3, 2021·Vaccines·Pietro Speziale, Giampiero Pietrocola
Jul 6, 2021·Clinical & Translational Immunology·Behnoush SoltanmohammadiFatemeh Rahimi-Jamnani

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