Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors.

Nina M Van Sorge,Liwen Deng,Eric J Sundberg,Alexej Schmidt,Gunnar Lindahl,Kelly S Doran,Mykola Lyndin,Bernhard B Singer,Daniel A Bonsor,Verena Schmitt,Erik Lindahl,Jaime Brizuela,Alex J Mccarthy,Olof R Nilsson,Elena Boero,Jos A G Van Strijp

doi:10.15252/embj.2020106103

Abstract

Streptococcus agalactiae, also known as group B Streptococcus (GBS), is the major cause of neonatal sepsis in humans. A critical step to infection is adhesion of bacteria to epithelial surfaces. GBS adhesins have been identified to bind extracellular matrix components and cellular receptors. However, several putative adhesins have no host binding partner characterised. We report here that surface‐expressed β protein of GBS binds to human CEACAM1 and CEACAM5 receptors. A crystal structure of the complex showed that an IgSF domain in β represents a novel Ig‐fold subtype called IgI3, in which unique features allow binding to CEACAM1. Bioinformatic assessment revealed that this newly identified IgI3 fold is not exclusively present in GBS but is predicted to be present in adhesins from other clinically important human pathogens. In agreement with this prediction, we found that CEACAM1 binds to an IgI3 domain found in an adhesin from a different streptococcal species. Overall, our results indicate that the IgI3 fold could provide a broadly applied mechanism for bacteria to target CEACAMs.

Highlights

Streptococcus agalactiae, known as group B Streptococcus (GBS), is the major cause of neonatal sepsis in humans
We show here that a novel Ig-like fold in different streptococcal adhesins promotes binding to human carcinoembryonic antigen-related cell adhesion molecules (CEACAM) receptors
Molecular analysis of this domain in the b protein from GBS demonstrated that the Ig-like domain binds to the N-terminal domain of human CEACAM1 and CEACAM5

Summary

Introduction

Streptococcus agalactiae, known as group B Streptococcus (GBS), is the major cause of neonatal sepsis in humans. GBS adhesins have been identified to bind extracellular matrix components and cellular receptors. We report here that surfaceexpressed b protein of GBS binds to human CEACAM1 and CEACAM5 receptors. A crystal structure of the complex showed that an IgSF domain in b represents a novel Ig-fold subtype called IgI3, in which unique features allow binding to CEACAM1. Bioinformatic assessment revealed that this newly identified IgI3 fold is not exclusively present in GBS but is predicted to be present in adhesins from other clinically important human pathogens. In agreement with this prediction, we found that CEACAM1 binds to an IgI3 domain found in an adhesin from a different streptococcal species. Our results indicate that the IgI3 fold could provide a broadly applied mechanism for bacteria to target CEACAMs

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Conclusion