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Single-cell Sequencing of Circulating Human Plasmablasts during Staphylococcus aureus Bacteremia
Priscilla F Kerkman1, Lisanne de Vor1, Thomas W van der Vaart2,3
1Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Journal of Immunology (Baltimore, Md. : 1950)
|October 25, 2024
Summary
Researchers identified four new monoclonal antibodies (mAbs) targeting Staphylococcus aureus surface components from bacteremia patients. These antibodies show potential for treating infections caused by S. aureus and Staphylococcus epidermidis.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Staphylococcus aureus causes severe healthcare-associated infections with high mortality.
- Current antibiotic treatments for S. aureus bacteremia are often insufficient.
- Discovering novel therapeutic antibodies is crucial for combating S. aureus infections.
Purpose of the Study:
- To investigate circulating plasmablast responses in patients with S. aureus bacteremia.
- To identify novel monoclonal antibodies (mAbs) targeting S. aureus.
- To analyze the functional activity and target specificity of identified mAbs.
Main Methods:
- Collected peripheral blood from 17 S. aureus bacteremia patients.
- Utilized single-cell transcriptome sequencing and Ig gene sequencing of plasmablasts.
- Synthesized recombinant IgGs from unique antibody sequences and tested for S. aureus binding.
Main Results:
- Identified over 300 unique variable heavy and light Ig sequences from >400 plasmablasts.
- Discovered four novel mAbs that bind specifically to the S. aureus surface.
- Three of the four mAbs exhibited cross-reactivity with Staphylococcus epidermidis.
- Target identification revealed mAbs binding to wall teichoic acid (WTA) and lipoteichoic acid (LTA).
- All identified mAbs induced Fc-dependent phagocytosis of staphylococci by neutrophils.
Conclusions:
- Characterized active B cell responses during S. aureus infection.
- Identified four functional mAbs targeting the S. aureus surface, with potential therapeutic applications.
- Demonstrated cross-reactivity of some mAbs with S. epidermidis, suggesting broader utility.
- Highlighted the role of WTA and LTA as targets for anti-staphylococcal antibodies.
