Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis

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.