Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis
Catton, Erin A.; Bonsor, Daniel A.; Herrera, Carolina; Stålhammar-Carlemalm, Margaretha; Lyndin, Mykola; Turner, Claire E.; Soden, Jo; van Strijp, Jos A.G.; Singer, Bernhard B.; van Sorge, Nina M.; Lindahl, Gunnar; McCarthy, Alex J.
(2023) Nature Communications, volume 14, issue 1
(Article)
Abstract
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
... read more
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.
show less
Download/Full Text
Keywords: General Chemistry, General Biochemistry,Genetics and Molecular Biology, General, General Physics and Astronomy
ISSN: 2041-1723
Publisher: Nature Publishing Group
Note: Funding Information: This manuscript is dedicated to the life of Bernhard B. Singer who passed away in January 2023 after the experimental part of this work and drafting of the manuscript was completed. We would like to thank the CDC (USA) and Shiranee Sriskandan (Imperial College London) for access to clinical S. pyogenes strains. We thank the Department of Surgery and Cancer and the Department of Obstetrics and Gynaecology at St. Mary’s Hospital, Imperial College for their assistance in obtaining human tissue. We thank York Tissue Bank, York Biomedical Research Institute, University of York, UK for access to human ecto-cervical explants. We thank staff at the Flow Cytometry Facility and High-Throughput Single Cell Analysis (HTSCA) Facility for technical assistance. We thank Carla J.C. de Haas, Piet Aerts, Kok P.M. van Kessel (UMC Utrecht, Utrecht, The Netherlands), and Birgit Maranca-Hüwel, Bärbel Gobs-Hevelke (University of Duisburg-Essen, Germany) for technical support. We thank the staff of Beamlines 12-2 and ID23-D at the Stanford Synchrotron Radiation Lightsource and the Advanced Photon Source, respectively, for support in data collection. This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement 700862 (A.J.M. and J.A.G.V.S.), the Medical Research Council through the Doctoral Training Award MR/N014103/ to Imperial College London (E.A.C. and A.J.M.), the Biotechnology and Biological Sciences Research Council award BB/V006495/1 (A.J.M.), Royal Society Research Grant RGS\R1\201044 (A.J.M.), Deutsche Forschungsgemeinschaft DFG grant SI-1558/6-1 (B.B.S.), The Swedish Research Council grant K2011-56X-09490-21-6 (G.L.), a Vidi grant (91713303) from the Dutch Research Council for Health Research and Development (ZonMW; N.M.v.S.), and The Foundation Olle Engkvist Byggmästare (G.L.). Funding Information: This manuscript is dedicated to the life of Bernhard B. Singer who passed away in January 2023 after the experimental part of this work and drafting of the manuscript was completed. We would like to thank the CDC (USA) and Shiranee Sriskandan (Imperial College London) for access to clinical S. pyogenes strains. We thank the Department of Surgery and Cancer and the Department of Obstetrics and Gynaecology at St. Mary’s Hospital, Imperial College for their assistance in obtaining human tissue. We thank York Tissue Bank, York Biomedical Research Institute, University of York, UK for access to human ecto-cervical explants. We thank staff at the Flow Cytometry Facility and High-Throughput Single Cell Analysis (HTSCA) Facility for technical assistance. We thank Carla J.C. de Haas, Piet Aerts, Kok P.M. van Kessel (UMC Utrecht, Utrecht, The Netherlands), and Birgit Maranca-Hüwel, Bärbel Gobs-Hevelke (University of Duisburg-Essen, Germany) for technical support. We thank the staff of Beamlines 12-2 and ID23-D at the Stanford Synchrotron Radiation Lightsource and the Advanced Photon Source, respectively, for support in data collection. This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement 700862 (A.J.M. and J.A.G.V.S.), the Medical Research Council through the Doctoral Training Award MR/N014103/ to Imperial College London (E.A.C. and A.J.M.), the Biotechnology and Biological Sciences Research Council award BB/V006495/1 (A.J.M.), Royal Society Research Grant RGS\R1\201044 (A.J.M.), Deutsche Forschungsgemeinschaft DFG grant SI-1558/6-1 (B.B.S.), The Swedish Research Council grant K2011-56X-09490-21-6 (G.L.), a Vidi grant (91713303) from the Dutch Research Council for Health Research and Development (ZonMW; N.M.v.S.), and The Foundation Olle Engkvist Byggmästare (G.L.). Publisher Copyright: © 2023, The Author(s).
(Peer reviewed)
