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bioRxiv · 10.1101/2023.10.17.562767

Mechanism of 2-Fucosyllactose degradation by Human-Associated Akkermansia

Fricker, A. D.·Padilla, L.·Luna, E.·Choudhury, B.·Hughes, E. R.·Panzetta, M. E.·Valdivia, R.·Flores, G. E.
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Abstract

Among the first microorganisms to colonize the human gut of breastfed infants are bacteria capable of fermenting human milk oligosaccharides (HMOs). One of the most abundant HMOs, 2-fucosyllactose (2-FL), may specifically drive bacterial colonization of the intestine. Recently, differential growth has been observed across multiple species of Akkermansia on various HMOs including 2FL. In culture, we found growth of two species, A. muciniphila MucT and A. biwaensis CSUN-19, in HMOS corresponded to a decrease in the levels of 2-FL and an increase in lactose, indicating that the first step in 2-FL catabolism is the cleavage of fucose. Using phylogenetic analysis and transcriptional profiling, we found that the number and expression of fucosidase genes from two glycoside hydrolase (GH) families, GH29 and GH95, varies between these two species. During mid-log phase growth, the expression of several GH29 genes was increased by 2-FL in both species, whereas the GH95 genes were induced only in A. muciniphila. We further show that one putative fucosidase and a {beta}-galactosidase from A. biwaensis are involved in the breakdown of 2-FL. Our findings indicate that that plasticity of GHs of human associated Akkermansia sp. enable access to additional growth substrates present in HMOs, including 2-FL. Our work highlights the potential for Akkermansia to influence the development of the gut microbiota early in life and expands the known metabolic capabilities of this important human symbiont. IMPORTANCEAkkermansia are mucin degrading specialists widely distributed in the human population. Akkermansia biwaensis has recently been observed to have enhanced growth relative to other human associated Akkermansia on multiple human milk oligosaccharides (HMOs). However, the mechanisms for enhanced growth are not understood. Here, we characterized the phylogenetic diversity and function of select genes involved in growth of A. biwaensis on 2-fucosyllactose (2-FL), a dominant HMO. Specifically, we demonstrate that two genes in a genomic locus, a putative {beta}-galactosidase and -fucosidase, are likely responsible for the enhanced growth on 2-FL. The functional characterization of A. biwaensis growth on 2-FL delineates the significance of a single genomic locus that may facilitate enhanced colonization and functional activity of select Akkermansia early in life.

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Fricker, A. D., Padilla, L., Luna, E., Choudhury, B., Hughes, E. R., Panzetta, M. E., Valdivia, R., Flores, G. E.. 2023-10-17. Mechanism of 2-Fucosyllactose degradation by Human-Associated Akkermansia. https://doi.org/10.1101/2023.10.17.562767

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