Unstudied function and diversity of bacterial lectins found in the human intestinal commensal microbiome

A group from Department of Medicine, Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA, etc. has reported about unstudied function and diversity of bacterial lectins found in the human intestinal commensal microbiome.

One commensal bacterial effector gene (Cbeg) family that was found in commensal intestinal bacteria of multiple patient stool samples is composed of uncharacterized genes predicted to encode for lectins (e.g., Cbeg4 and Cbeg5).

A predicted domain analysis of Cbeg4 and Cbeg5 revealed both genes encode proteins containing a secretion signal peptide, a fibronectin type 3 domain (Fn; IPR003961) and a carbohydrate-binding module domain (CBM, CBM6-CBM35-CBM36_like_2, IPR033803). Among 865 proteins found in the Uniprot database that are predicted to contain a CBM6-CBM35-CBM36_like_2 carbohydrate-binding domain, 108 different domain architectures and only 2 functionally characterized proteins were identified. The two functionally characterized proteins with a CBM6-CBM35-CBM36_like_2 domain are enzymes and not lectins; one is a xanthan lyase isolated from Bacillus sp. GL1 and the other is a golgi trafficking enzyme (golvesin) isolated from Dyctostelium discoideum. Analysis of the Cbeg4 and Cbeg5 protein sequence by SWISS-MODEL suggests Cbeg4 and Cbeg5 exist as monomeric proteins. The domain architecture of Cbeg4 and Cbeg5 is specific to commensal Bacteroides species and is distinct from any functionally characterized lectins.

Glycan structures that bound to either CBM4 or CBM5 share a common Galβ1–3GlcNacβ1–2Manα1–3Man motif. In human glycomics data from the Glyconnect database, this N-linked glycan sub-structure is most frequently seen in datasets generated from peripheral blood mononuclear cells (PBMC). Based on their domain content and glycan-binding properties Cbeg4 and Cbeg5 appear to be lectins that bind leukocyte-associated N-linked glycan motifs.

Actually, for CD14+ monocytes, CD16+ monocytes, and cDC2 dendritic cells Cbeg5 increased IL-1β, IL-6, IL-8, IL-10 and TNFα in a dose-dependent manner. Cbeg5 also affected cytokine production in CD1c−CD14−CD16−CD11c+ myeloid cells (mCD11c). The induction of cytokines in these four cell populations (CD14+ monocytes, CD16+ monocytes, cDC2 dendritic cells, and mCD11c cells) was striking with a >100-fold increase relative to the PBS control. To date the role of lectins in the human microbiome has focused on their function as adhesins or in the binding and transport of glycans for bacterial metabolism. The functional analysis of Cbeg5 exampled in interaction with PBMCs mentioned above suggests the diversity of lectin functions in the human microbiome may extend to regulation of the mucosal immune system.

Those lectins encoded by human microbiota represent a biologically relevant, functionally diverse, but yet largely unstudied. The systematic investigation of these lectins will improve our understanding of how the human microbiome contributes to health and disease.