Placental colonization by Fusobacterium nucleatum is mediated by binding of the Fap2 lectin to placentally displayed Gal-GalNAc

Lishay Parhi, Jawad Abed, Amjad Shhadeh, Tamar Alon-Maimon, Shiran Udi, Shani Leviatan Ben-Arye, Joseph Tam, Oren Parnas, Vered Padler-Karavani, Debra Goldman-Wohl, Simcha Yagel, Ofer Mandelboim*, Gilad Bachrach

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

While the existence of an indigenous placental microbiota remains controversial, several pathogens are known to be involved in adverse pregnancy outcomes. Fusobacterium nucleatum is an oral bacterium that is one of several bacteria associated with preterm birth. Oral fusobacteria translocate to the placenta hematogenously; however, the mechanisms localizing them to the placenta remain unclear. Here, using peanut agglutinin, we demonstrate that the level of Gal-GalNAc (Galβ1−3GalNAc; Thomsen Friedenreich antigen) found on trophoblasts facing entering maternal blood rises during gestation and is recognized by the fusobacterial Fap2 Gal-GalNAc lectin. F. nucleatum binding to human and mouse placenta correlates with Gal-GalNAc levels and is reduced upon O-glycanase treatment or with soluble Gal-GalNAc. Fap2-inactivated F. nucleatum shows reduced binding to Gal-GalNAc-displaying placental sections. In a mouse model, intravenously injected Fap2-expressing F. nucleatum, but not a Fap2 mutant, reduces mouse fetal survival by 70%.

Original languageAmerican English
Article number110537
JournalCell Reports
Volume38
Issue number12
DOIs
StatePublished - 22 Mar 2022

Bibliographical note

Funding Information:
The authors thank the donors, the RCWIH BioBank, the Blumenfeld-Tanenbaum Research Institute, and the Mount Sinai Hospital/UHN Department of Obstetrics & Gynecology for the human specimens used in this study (http://biobank.lunenfeld.ca); Professor Norman Grover for his valuable assistance in statistics; Dr. Zakhariya Manevitch and Dr. Yael Feinstein-Rotkopf for their valuable help in microcopy; and Noam Koren and Dr. Oded Heyman for their valuable discussion. This work was supported by the Israel Cancer Research Fund Project grant, the Israel Science Foundation Moked grant, and the Israel Ministry of Science and Technology Personalized Medicine grant. L.P. S.Y. D.G.-W. O.M. and G.B. conceived of the research idea, designed experiments, and wrote the article. D.G.-W. and S.Y. helped interpret clinical data for this article. L.P. and V.P.-K. designed and performed in vitro and in vivo experiments. J.A. A.S. T.A.-M. S.U. S.L.B.-A. and O.P. helped perform in vitro and in vivo experiments. J.T. helped create critical reagents. The authors declare no competing interests.

Funding Information:
The authors thank the donors, the RCWIH BioBank, the Blumenfeld-Tanenbaum Research Institute, and the Mount Sinai Hospital/UHN Department of Obstetrics & Gynecology for the human specimens used in this study ( http://biobank.lunenfeld.ca ); Professor Norman Grover for his valuable assistance in statistics; Dr. Zakhariya Manevitch and Dr. Yael Feinstein-Rotkopf for their valuable help in microcopy; and Noam Koren and Dr. Oded Heyman for their valuable discussion. This work was supported by the Israel Cancer Research Fund Project grant, the Israel Science Foundation Moked grant, and the Israel Ministry of Science and Technology Personalized Medicine grant .

Publisher Copyright:
© 2022 The Authors

Keywords

  • CP: Developmental biology
  • CP: Microbiology
  • Fusobacterium nucleatum
  • Gal-GalNAc
  • adverse pregnancy outcomes
  • placenta

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