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

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.

Bonsor, Daniel A.University of Maryland, Baltimore (author)
Herrera, CarolinaImperial College London (author)
Stålhammar-Carlemalm, MargarethaLund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)mmb-msc (author)
Lyndin, MykolaUniversity Hospital Essen,Sumy State University (author)
Turner, Claire E.University of Sheffield (author)
Soden, Jo (author)
van Strijp, Jos A.G.University Medical Center Utrecht (author)
Singer, Bernhard B.University of Duisburg-Essen (author)
van Sorge, Nina M.University Medical Center Utrecht,Academic Medical Center of University of Amsterdam (AMC) (author)
Lindahl, GunnarLund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Teknisk mikrobiologi,Centrum för tillämpade biovetenskaper,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine,Applied Microbiology,Center for Applied Life Sciences,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)mmb-gli (author)
McCarthy, Alex J.University Medical Center Utrecht,Imperial College London (author)
Imperial College LondonUniversity of Maryland, Baltimore (creator_code:org_t)

By the author/editor: Catton, Erin A.; Bonsor, Daniel A ...; Herrera, Carolin ...; Stålhammar-Carle ...; Lyndin, Mykola; Turner, Claire E ...; show more...; Soden, Jo; van Strijp, Jos ...; Singer, Bernhard ...; van Sorge, Nina ...; Lindahl, Gunnar; McCarthy, Alex J ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Microbiology in ...

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