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Published on: February 23, 2014
Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis
Erin A Catton1, Daniel A Bonsor2,3, Carolina Herrera4
1Centre for Bacterial Resistance Biology, Section of Molecular Microbiology, Department of Infectious Diseases, Imperial College London, London, SW7 2AZ, UK.
Insights
Bacterial R28 protein targets human CEACAM1, driving puerperal sepsis development by promoting adhesion and immune evasion. This molecular insight clarifies pathogenesis for this historically significant childbirth infection.
Area of Science:
- Microbiology and Immunology
- Molecular Pathogenesis
- Obstetric Infections
Background:
- Puerperal sepsis, a life-threatening infection post-childbirth, historically caused epidemics and remains a global health concern.
- Streptococcus pyogenes is linked to puerperal sepsis outbreaks, but its specific disease mechanisms are poorly understood.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying puerperal sepsis pathogenesis.
- To investigate the role of the bacterial R28 protein in Streptococcus pyogenes-associated puerperal sepsis.
Main Methods:
- Investigated the interaction between the bacterial R28 protein and human cell receptors.
- Utilized high-resolution structural analysis to determine the binding interface between R28 and CEACAM1.
- Assessed the functional consequences of the R28-CEACAM1 interaction on host cells and immune responses.
Main Results:
- The bacterial R28 protein specifically targets and binds to the human CEACAM1 receptor.
- This interaction promotes bacterial adhesion to cervical cells, impairs epithelial wound repair, and suppresses innate immune responses.
- Structural analysis revealed an IgI3-like fold in R28 responsible for binding the N-terminal domain of CEACAM1.
Conclusions:
- A single adhesin-receptor interaction (R28-CEACAM1) can drive the pathogenesis of bacterial sepsis.
- This study provides crucial molecular insights into the mechanisms of puerperal sepsis, a historically significant infectious disease.
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 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.
