Glycan cross-feeding drives mutualism betweenFusobacteriumand the vaginal microbiota

Abstract

Dysbiosis of the vaginal microbiome is associated with vaginal colonization by potential pathogens including Fusobacterium nucleatum, a bacterium linked with intrauterine infection and preterm birth. However, mechanisms by which such pathogens gain a foothold in the dysbiotic vagina remain obscure. Here we demonstrate that sialidase activity, a biochemical marker of vaginal dysbiosis, promoted F. nucleatum foraging on mammalian sialoglycans, an otherwise inaccessible resource. In mice with sialidase-positive vaginal microbiomes, mutant F. nucleatum unable to consume sialic acids displayed impaired colonization. Furthermore, community-and co-culture experiments showed that F. nucleatum did not simply take advantage of sialidase-positive bacteria, but also "gave back" to the community, supporting robust outgrowth of sialidase-producers, including Gardnerella vaginalis. These results illustrate that mutualistic relationships between vaginal bacteria support pathogen colonization and reinforce dysbiosis, adding complexity to the simplistic dogma that the mere absence of "healthy" lactobacilli is what creates a permissive environment for pathogens during dysbiosis.

Development of a Xylose-Inducible Promoter and Riboswitch Combination System for Manipulating Gene Expression inFusobacterium nucleatum

“…To evaluate this expectation, we created the plasmid pBCG06(xylR-E-luc), which was specifically designed to express the Luciola red luciferase gene (luc) under the control of the XISriboswitch (Figure 1E). The Luciola red luciferase offers greater sensitivity and brighter luminescence than Firefly luciferase (43), which we previously used as a reporter for gene expression monitoring in F. nucleatum (17). We introduced the plasmid into F. nucleatum and cultured the cells.…”

“…F. nucleatum has been reported to utilize glucose and possess a CcpA protein (43), often resulting in catabolite repression of sugar utilization in certain bacteria. To examine if glucose affects this hybrid system, we added 20 mM glucose along with 2% xylose and 2 mM theophylline to a culture.…”