Sialoglycan foraging drives mutualism between Fusobacterium nucleatum and the vaginal microbiota Kavita Agarwal1, Lloyd Robinson1, Justin Perry1, Lynne Foster1, Hueylie Lin1, Brett Tortelli1, Nicole Gilbert2, Warren Lewis1, Amanda Lewis1,2* Departments of 1Molecular Microbiology & 2Obstetrics and Gynecology, Washington University in St. Louis *Corresponding Author
Bacterial vaginosis (BV), a common vaginal dysbiosis, is characterized by low numbers of healthy Lactobacillus spp. and the overgrowth of diverse anaerobic bacteria. Women with BV are more likely to be vaginally colonized with Fusobacterium nucleatum, a pathogen frequently isolated from amniotic fluid in cases of pre-term birth. However, mechanisms employed by F. nucleatum during vaginal colonization have not been studied. A characteristic biochemical feature of BV is the presence of vaginal sialidase activity. Sialidases are enzymes that can liberate sialic acids from oligosaccharide chains decorating mammalian cell surface glyco-conjugates. While F. nucleatum does not produce its own sialidase it is often found colonizing with other sialidase producing bacteria, which could allow metabolic cross feeding of this opportunistic pathogen. Therefore, we hypothesize that sialic acid catabolism may facilitate vaginal colonization by F. nucleatum in the presence of sialidase activity. Our studies show that sialic acids are depleted from the vaginal epithelial cell surface, and free sialic acids are present at significantly higher concentration in vaginal fluids of women with BV. We also show that F. nucleatum can uptake and metabolize free sialic acid liberated by sialidases from BV associated pathogens such as Gardnerella vaginalis. Studies using a mouse vaginal colonization model revealed that F. nucleatum mutant defective in sialic acid consumption cleared significantly faster, than the wild-type counterpart, from mouse vaginas with sialidase producing microbiota. Interestingly, further studies revealed that F.nucleatum also provides reciprocal benefits to the sialidase producing bacteria in vaginal microbial communities, resulting in higher levels of sialidase activity and increased numbers of sialidase producers such as G. vaginalis. Taken together, these data provide the first mechanistic glimpse of how sialidase activity, one of the hallmark features of BV, may help to create a more hospitable environment for potential reproductive tract pathogens such as F. nucleatum.
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