Alty, J. W. | bioRxiv Science

bioRxiv2025

Intelectin-2 is a broad-spectrum antimicrobial lectin

Mammals regulate the localization, composition, and activity of their native microbiota at colonization sites. Lectins residing at these sites influence microbial populations, but their individual functions are often unclear. Intelectins are found in chordates at mucosal barriers, but their functions are not well characterized. We found that mouse intelectin-2 (mItln2) and human intelectin-2 (hItln2) engage and crosslink mucins via carbohydrate recognition. Moreover, both lectins recognize microbes within native microbial communities, including gram-positive and gram-negative isolates from the respiratory and gastrointestinal tracts. This ability to engage mammalian and microbial glycans arises from calcium-coordinated binding of carbohydrate residues within mucus and microbial surfaces. Microbes, but not human cells, bound by mItln2 or hItln2, suffer a loss of viability. These findings underscore the crucial antimicrobial role of mammalian intelectin-2 in mucosal defense, where it plays offensive (microbial killing) and defensive (mucus crosslinking) roles in regulating microbial colonization.

microbiology↗

bioRxiv2025

Synthetic Mucins as Glycan-Defined Prebiotics

The human microbiome contains at least as many bacterial cells as human cells. The mucosal layer that lines all epithelial cells organizes, cultivates, and regulates these bacterial inhabitants. Some commensal bacteria offer benefits, like improving gut barrier function, suppressing pathobiont growth, and modulating host immunity. These health benefits have fueled the popularity of probiotics, but their retention is often hindered by their low colonization efficiency and mucosal adhesion. Mucins, the primary structural components of the mucosal layer, are essential for the organization and regulation of microbial populations, promoting growth and offering sites for adhesion through their multivalent presentation of O-glycosylation. The molecular mechanisms of mucin- probiotic interactions remain understudied due, in part, to the inability to incisively manipulate native mucin sequences or the glycans they bear. In this investigation, we developed synthetic mucins with defined glycan presentations to interrogate glycan-dependent interactions between mucus and probiotic Lactobacillus species. Though synthetic mucins can dampen the effects of pathogens, toxins, and viruses, their impact on probiotic bacteria as prebiotics or binding sites is unclear. We synthesized mucin surrogates that bind to three investigated Lactobacillus species. The nutrient conditions under which bacteria were cultured influenced glycan binding preferences, suggesting mucin-probiotic interactions change with nutrient availability. The addition of synthetic mucins to native mucin increased Lactobacillus fermentum adherence. Additionally, an increase in Lactobacillus glycosidase activity indicated that native and synthetic mucins both function as prebiotics, as probiotic bacteria can cleave the displayed O-glycans. Thus, synthetic mucins can cultivate target probiotic bacteria and increase adhesion as binding sites, highlighting their value as tools for elucidating native mucin functions and as promising agents for promoting human health.

biochemistry↗