Our new paper from Erin Catton - PhD student in the lab - was published in April in Nature Communications. Congratulations Erin and all our collaborators.
Life-threatening bacterial infections in women after childbirth, known as puerperal sepsis, resulted in classical epidemics and remain a global health problem. Outbreaks of life-threatening bacterial infections in women after childbirth arose in the 18th Century and are ascribed to Streptococcus pyogenes (also known as Group A Streptococcus or Strep A) that express an adhesin called R28. In this project, we show that these bacteria target a human immune receptor called CEACAM1. We investigated the mechanism of interactions using structural and biochemical approaches, and the functions of these interactions using cell and tissue infection models.
We found
The R28 protein binds to CEACAM1 with high specificity.
The interaction promotes the adhesion of S. pyogenes to cervical epithelial cells and suppresses closure of wounds within cervical cell monolayers.
R28-CEACAM1 interactions enhance the innate immune response against S. pyogenes, including suppression of cytokine production, phagocytosis and killing.
In collaboration with Daniel Bonsor, Carolina Herrera, Margaretha Stålhammar-Carlemalm, Mykola Lyndin, Claire Turner, Jo Soden, Jos van Strijp, Bernhard Singer, Nina van Sorge, and Gunnar Lindahl G.
In memory of Bernhard Singer
Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis
Catton EA, Bonsor DA, Herrera C, Stålhammar-Carlemalm M, Lyndin M, Turner CE, Soden J, van Strijp JAG, Singer BB, van Sorge NM, Lindahl G, McCarthy AJ.
Nat Commun. 2023 Apr 20;14(1):2275. doi: 10.1038/s41467-023-37732-1.
https://www.nature.com/articles/s41467-023-37732-1
Artwork of S. pyogenes by Medicosage
(https://medicosage.com/streptococcus-pyogenes/)