Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis (vol 14, 2275, 2023)

被引：1

作者：

Catton, Erin A.

Bonsor, Daniel A.

Herrera, Carolina

Stalhammar-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.

机构：

[1] Centre for Bacterial Resistance Biology, Section of Molecular Microbiology, Department of Infectious Diseases, Imperial College London, London

[2] University of Maryland, Baltimore, 21201, MD

[3] NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD

[4] Section of Immunology of Infection, Department of Infectious Disease, Imperial College London, London

[5] Department of Laboratory Medicine, Division of Medical Microbiology, Lund University, Lund

[6] Sumy State University, Sumy

[7] Institute of Anatomy, Medical Faculty, University of Duisburg-Essen, Essen

[8] The School of Biosciences, The Florey Institute, The University of Sheffield, Sheffield

[9] Retrogenix, Chinley, High Peak, Chinley

[10] Department of Medical Microbiology, UMC Utrecht, Utrecht

[11] Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam

[12] Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam UMC, location AMC, Amsterdam

[13] Department of Chemistry, Division of Applied Microbiology, Lund University, Lund

来源：

NATURE COMMUNICATIONS | 2023年 / 14卷 / 01期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会; 荷兰研究理事会; 瑞典研究理事会; 欧盟地平线“2020”;

关键词：

D O I：

10.1038/s41467-023-38372-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. © 2023, The Author(s).

引用

页数：1