The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem 9112001, Israel.
Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel.
Cell Rep. 2022 Mar 22;38(12):110537. doi: 10.1016/j.celrep.2022.110537.
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%.
虽然本土胎盘微生物组的存在仍然存在争议，但已知有几种病原体与不良妊娠结局有关。核梭杆菌是一种口腔细菌，是与早产相关的几种细菌之一。口腔梭杆菌通过血源性转移到胎盘；然而，将其定位到胎盘的机制尚不清楚。在这里，我们使用花生凝集素表明，在妊娠期间，面对进入母体血液的滋养层上发现的 Gal-GalNAc（Galβ1-3GalNAc；Thomson-Friedenreich 抗原）的水平升高，并被梭杆菌的 Fap2 Gal-GalNAc 凝集素识别。F. nucleatum 与人和小鼠胎盘的结合与 Gal-GalNAc 水平相关，并且在用 O-糖基酶处理或用可溶性 Gal-GalNAc 处理后减少。Fap2 失活的 F. nucleatum 显示与显示 Gal-GalNAc 的胎盘切片的结合减少。在小鼠模型中，静脉注射表达 Fap2 的 F. nucleatum，但不是 Fap2 突变体，可使小鼠胎儿存活率降低 70%。
