Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis.
Erin A Catton, Daniel A Bonsor, Carolina Herrera, Margaretha Stålhammar-Carlemalm, Mykola Lyndin, Claire E Turner, Jo Soden, Jos A G van Strijp, Bernhard B Singer, Nina M van Sorge, Gunnar Lindahl, Alex J McCarthy
Author Information
Erin A Catton: Centre for Bacterial Resistance Biology, Section of Molecular Microbiology, Department of Infectious Diseases, Imperial College London, London, SW7 2AZ, UK.
Daniel A Bonsor: University of Maryland, Baltimore, MD, 21201, USA.
Carolina Herrera: Section of Immunology of Infection, Department of Infectious Disease, Imperial College London, London, W2 1NY, UK.
Margaretha Stålhammar-Carlemalm: Department of Laboratory Medicine, Division of Medical Microbiology, Lund University, Lund, 223 62, Sweden.
Mykola Lyndin: Sumy State University, Sumy, 40000, Ukraine.
Claire E Turner: The School of Biosciences, The Florey Institute, The University of Sheffield, Sheffield, S10 2TN, UK. ORCID
Jo Soden: Retrogenix, Chinley, High Peak, SK23 6FJ, Chinley, UK.
Jos A G van Strijp: Department of Medical Microbiology, UMC Utrecht, Utrecht, 3584 CX, The Netherlands. ORCID
Bernhard B Singer: Institute of Anatomy, Medical Faculty, University of Duisburg-Essen, Essen, 45147, Germany.
Nina M van Sorge: Department of Medical Microbiology, UMC Utrecht, Utrecht, 3584 CX, The Netherlands. n.m.vansorge@amsterdamumc.nl. ORCID
Gunnar Lindahl: Department of Laboratory Medicine, Division of Medical Microbiology, Lund University, Lund, 223 62, Sweden. gunnar.lindahl@tmb.lth.se. ORCID
Alex J McCarthy: Centre for Bacterial Resistance Biology, Section of Molecular Microbiology, Department of Infectious Diseases, Imperial College London, London, SW7 2AZ, UK. a.mccarthy@imperial.ac.uk. ORCID
Life-threatening bacterial infections in women after childbirth, known as puerperal sepsis, resulted in classical epidemics and remain a global health problem. While outbreaks of puerperal sepsis have been ascribed to Streptococcus pyogenes, little is known about disease mechanisms. Here, we show that the bacterial R28 protein, which is epidemiologically associated with outbreaks of puerperal sepsis, specifically targets the human receptor CEACAM1. This interaction triggers events that would favor the development of puerperal sepsis, including adhesion to cervical cells, suppression of epithelial wound repair and subversion of innate immune responses. High-resolution structural analysis showed that an R28 domain with IgI3-like fold binds to the N-terminal domain of CEACAM1. Together, these findings demonstrate that a single adhesin-receptor interaction can drive the pathogenesis of bacterial sepsis and provide molecular insights into the pathogenesis of one of the most important infectious diseases in medical history.
