A joint collaboration between ten research groups unveils a resistance mechanism of the pathogen bacteria involved in colorectal cancer Fusobacterium nucleatum.

Colorectal cancer pathogenesis and progression is associated with the presence of Fusobacterium nucleatum and the reduction of acetylated derivatives of spermidine, as well as dietary components such as tannin-rich foods. We show that a new tannase orthologue of F. nucleatum (TanFnn) has significant structural differences with its Lactobacillus plantarum counterpart affecting the flap covering the active site and the accessibility of substrates. Crystallographic and molecular dynamics analysis revealed binding of polyamines to a small cavity that connects the active site with the bulk solvent which interact with catalytically indispensable residues. As a result, spermidine and its derivatives, particularly N8-acetylated spermidine, inhibit the hydrolytic activity of TanFnn and increase the toxicity of gallotannins to F. nucleatum. Our results support a model in which the balance between the detoxicant activity of TanBFnn and the presence of metabolic inhibitors can dictate either conducive or unfavorable conditions for the survival of F. nucleatum.

Publication: A structurally unique Fusobacterium nucleatum tannase provides detoxicant activity against gallotannins and pathogen resistance Mancheño JM, Atondo E, Tomás-Cortázar J, Lavín JL, Plaza-Vinuesa L, Martín-Ruiz I, Barriales D, Palacios A, Navo CD, Sampedro L, Peña-Cearra A, Pascual-Itoiz MA, Castelo J, Carreras-González A, Castellana D, Pellón A, Delgado S, Ruas-Madiedo P, de las Rivas B, Abecia L, Muñoz R, Jiménez-Osés G, Anguita J y Rodríguez H. Microbial Biotechnology (2020); doi:10.1111/1751-7915.13732