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

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 (Gal beta 1-3GalNAc; 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%.

Automated summary

This study suggests that Fusobacterium nucleatum, an oral bacterium associated with preterm birth, binds to the placenta by recognizing Gal-GalNAc on trophoblasts. The binding is reduced with O-glycanase treatment or soluble Gal-GalNAc. In a mouse model, Fap2-expressing F. nucleatum reduces fetal survival, indicating a potential role in adverse pregnancy outcomes.