Streptococcus oralis induces platelet aggregation through coordinated GPIbα and FcγRIIA signalling
- 1Cardiovascular Infection Research Group, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin 2, Ireland
- 2Center for Microbe and Immunity Research, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
- 3Department of Pediatrics, The Ohio State University, Columbus, OH, USA
Abstract
Background:: Streptococcus oralis is the most prevalent viridans group streptococcus associated with infective endocarditis (IE), yet the platelet activation mechanisms that underpin its pathogenicity remain poorly defined. Platelet–bacterium interactions are central to vegetation formation, but the relative contributions of direct adhesion and antibody-dependent signaling in S. oralis-induced platelet aggregation are unclear.
Objectives:: To define the molecular mechanisms by which S. oralis induces platelet activation and aggregation, and to determine how bacterial adhesins and host factors cooperate to drive this response.
Methods:: Platelet aggregation and dense granule secretion were assessed using light transmission aggregometry and ATP release assays in platelet-rich plasma and washed platelets. An IE isolate of S. oralis and isogenic mutants lacking functional Fap1 were used alongside pharmacological and antibody-based inhibition of platelet receptors and signaling pathways.
Results:: S. oralis ATCC 10557 induced robust platelet aggregation with a characteristic lag phase and strong dense granule release. Aggregation required integrin αIIbβ3 signaling and was abolished by inhibition of glycoprotein Ibα (GPIbα) or FcγRIIA. Loss of the serine-rich repeat protein Fap1, or mutation of its conserved sialic acid-binding motif, abrogated platelet aggregation. While most donors required a plasma component for aggregation, supplementation of washed platelets with human IgG fully restored aggregation in a dose-dependent manner. Importantly, IgG was unable to bypass the requirement for Fap1–GPIbα interaction, indicating that direct bacterial adhesion is an essential initiating step that enables antibody-dependent FcγRIIA signaling. Substantial inter-individual variability was observed in aggregation kinetics and IgG dependence.
Conclusions:: S. oralis induces platelet aggregation through a dual, non-redundant mechanism requiring Fap1-mediated engagement of GPIbα and IgG-dependent FcγRIIA signaling. This cooperative pathway drives potent platelet activation and exhibits marked host-dependent variability. These findings provide new mechanistic insight into early events in IE pathogenesis and highlight platelet–bacterium interactions as potential targets for risk stratification and therapeutic intervention.
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BibTeX
@article{lamerton2026streptococcus,
title = {{Streptococcus oralis induces platelet aggregation through coordinated GPIbα and FcγRIIA signalling}},
author = {Rachel Lamerton and Amy McMahon and Adam O’Neill and Samantha King and Steven W. Kerrigan},
journal = {Platelets},
year = {2026},
month = oct,
doi = {10.1080/09537104.2026.2688088},
url = {https://europepmc.org/article/PMC/PMC13726873},
note = {CC BY},
}
RIS
TY - JOUR
TI - Streptococcus oralis induces platelet aggregation through coordinated GPIbα and FcγRIIA signalling
AU - Rachel Lamerton
AU - Amy McMahon
AU - Adam O’Neill
AU - Samantha King
AU - Steven W. Kerrigan
PY - 2026
DA - 2026/10/29
JO - Platelets
DO - 10.1080/09537104.2026.2688088
UR - https://europepmc.org/article/PMC/PMC13726873
AB - Background:: Streptococcus oralis is the most prevalent viridans group streptococcus associated with infective endocarditis (IE), yet the platelet activation mechanisms that underpin its pathogenicity remain poorly defined. Platelet–bacterium interactions are central to vegetation formation, but the relative contributions of direct adhesion and antibody-dependent signaling in S. oralis-induced platelet aggregation are unclear. Objectives:: To define the molecular mechanisms by which S. oralis induces platelet activation and aggregation, and to determine how bacterial adhesins and host factors cooperate to drive this response. Methods:: Platelet aggregation and dense granule secretion were assessed using light transmission aggregometry and ATP release assays in platelet-rich plasma and washed platelets. An IE isolate of S. oralis and isogenic mutants lacking functional Fap1 were used alongside pharmacological and antibody-based inhibition of platelet receptors and signaling pathways. Results:: S. oralis ATCC 10557 induced robust platelet aggregation with a characteristic lag phase and strong dense granule release. Aggregation required integrin αIIbβ3 signaling and was abolished by inhibition of glycoprotein Ibα (GPIbα) or FcγRIIA. Loss of the serine-rich repeat protein Fap1, or mutation of its conserved sialic acid-binding motif, abrogated platelet aggregation. While most donors required a plasma component for aggregation, supplementation of washed platelets with human IgG fully restored aggregation in a dose-dependent manner. Importantly, IgG was unable to bypass the requirement for Fap1–GPIbα interaction, indicating that direct bacterial adhesion is an essential initiating step that enables antibody-dependent FcγRIIA signaling. Substantial inter-individual variability was observed in aggregation kinetics and IgG dependence. Conclusions:: S. oralis induces platelet aggregation through a dual, non-redundant mechanism requiring Fap1-mediated engagement of GPIbα and IgG-dependent FcγRIIA signaling. This cooperative pathway drives potent platelet activation and exhibits marked host-dependent variability. These findings provide new mechanistic insight into early events in IE pathogenesis and highlight platelet–bacterium interactions as potential targets for risk stratification and therapeutic intervention.
SN - 0953-7104
SN - 1369-1635
ER -