Harnessing Gut Microbes for Glycan Detection and Quantification

ID# 2022-5420
Harnessing PUL-encoded machinery to detect distinct glycans

Technology Summary

Glycans are complex structurally diverse macromolecules abundant in the mammalian intestine. The gut microbiota composition is largely governed by the available glycans derived from the host diet, intestinal mucosa, and co-resident microbes. Gut microbes possess a vast repertoire of glycan-specific sensor proteins that facilitate rapid and dramatic changes in target gene transcription in response to target glycan availability, enabling their utilization as growth substrates. Penn State inventors have developed a reporter-based approach that specifically and sensitively harnesses these proteins to indicate the presence of structurally distinct glycans by reflecting PUL polysaccharide utilization loci (PUL) transcription.

The invention comprises a luciferase reporter optimized for Bacteroides species that can accurately reflect dose-dependent PUL transcription when coupled with PUL-regulatory elements. Thus, target glycans are readily detected in complex mixtures by quantifiable changes in bioluminescence.

Application & Market Utility

Tracking glycans associated with disease could inform potential disease biomarkers, therapeutic targets, and prebiotic compounds. The proposed invention overcomes typical glycomics barriers, such as glycan structural complexity and diversity in heterogenous mixtures, which limit high-throughput assays and require derivatized material.

The specificity of PUL-encoded surface glycan-binding proteins (SGBPs) also potentiates their use as affinity purification reagents to isolate PUL-target glycans from complex heterogenous mixtures when paired with a corresponding PUL-reporter, aiding in downstream glycan structural characterization.

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