Role of mucus and glycoprotein

degradation in the gut and vagina

​

        We are working to identify and define how enzymes from individual bacteria, as well as entire communities, break down host barriers, leading to invasive infection. This is particularly relevant to BV, a condition linked with higher risks of secondary infections. We showed that sialidases in BV can degrade sialic acids present in different linkages, different types of glycan chains, and from an array of glycoprotein substrates at the mucosa. We also demonstrated that sialic acid removal can lead to a successive process of deglycosylation of the carbohydrate residues on glycan chains and that this process increases the susceptibility of heavily glycosylated mucosal proteins to proteolysis. Using our animal model, we showed that the organism Gardnerella vaginalis engages in foraging of mucosal sialoglycans, leading to depletion of sialic acid levels from the mucosa, a phenotype also observed in human specimens. Our ongoing work in this area tests several distinct mechanistic hypotheses about the role of bacterial sialidases in vaginal colonization, including how those that produce the sialidases employ them in colonization or pathogenesis, as well as the mechanisms by which some bacteria may rely on sialidases produced by other members of the community for colonization or pathogenesis.

​

1. Lewis, WG; Robinson, LS; Perry, JC; Bick, JL; Peipert, JF; Allsworth, JE; Lewis, AL. 2012. Hydrolysis of Secreted Immunoglobulin A (IgA) in Ex Vivo and Biochemical Models of Bacterial Vaginosis. J Biol Chem. 287(3):2079-89. PMID: 22134918 PMCID: PMC3265887

2. Lewis WG, Robinson LS, Gilbert NM, Perry JC, Lewis AL. 2013 Degradation, Foraging, and Depletion of Mucus Sialoglycans by the Vagina-adapted Actinobacterium Gardnerella vaginalis. J Biol Chem. 2013 Apr 26;288(17):12067-79. doi: 10.1074/jbc.M113.453654. Epub 2013 Mar 11.PMID: 23479734 PMCID: PMC3636892

3. Robinson LS, Lewis WG, Lewis AL. The Sialylate O-acetylesterase EstA from Gut Bacteroides Species Enables Sialidase-Mediated Cross-species Foraging of 9-O-acetylated Sialoglycans. J Biol Chem. 2017 May 19. pii: jbc.M116.769232. doi: 10.1074/jbc.M116.769232. PMID: 28526748. PMCID: PMC5512079

4. Robinson LR, Schwebke J, Lewis WG, and Lewis AL. Identification and characterization of NanH2 and NanH3, the enzymes responsible for sialidase activity in Gardnerella vaginalis. 2019 J Biol Chem Feb 5. pii: jbc.RA118.006221. doi: 10.1074/jbc.RA118.006221. PMID: 30723162. PMCID: PMC6462536