# Chemical and biochemical tools to study the functions of exopolysaccharides in bacterial biofilms

> **NIH NIH R35** · UNIV OF MARYLAND, COLLEGE PARK · 2024 · $237,866

## Abstract

PROJECT SUMMARY/ABSTRACT:
 It is estimated that over 1.7 million hospital acquired infections per year in the U.S. result from microbial
biofilms. New approaches to specifically target and disrupt bacterial biofilms will thus have a significant impact
on human healthcare. Exopolysaccharides like poly-N-acetylglucosamine (PNAG) are critical biofilm
components that facilitate cell-cell interactions and serve as a protective barrier against the host’s immune
system and common antibiotic therapeutics used to treat bacterial infections. However, there is little is known
about the molecular interactions of PNAG with other biofilm EPS components. Blocking the interactions between
bacterial cells and PNAG or using glycosidase enzymes that break down PNAG and disrupt biofilms are attractive
approaches to treat biofilm infections.
 Overall, our goal is to characterize molecular interaction networks of exopolysaccharides like PNAG,
determine how they contribute to biofilm formation and dispersal, and develop novel strategies to treat biofilm
infections by blocking these interaction networks or by catalyzing the breakdown of critical biofilm EPS
components. To accomplish this overarching goal, we have identified two primary research areas for the next 5
years and plans for beyond. The first area seeks to develop tools for rapid identification of PNAG in bacterial
biofilms and develop a live cell proximity labeling platform for identification and subsequent characterization of
PNAG-binding proteins. These protein-carbohydrate binding interaction have the potential to be targets for new
anti-biofilm therapeutics. A second area will develop high-throughput approaches to identify and subsequently
engineer PNAG glycosidase enzymes through functional screening of environmental metagenomes and iterative
site saturation mutagenesis approaches. To enable these studies, we have developed new colorimetric and
fluorometric PNAG analogs that enable the high throughput identification of PNAG glycosidase activity. This
research will establish a platform in my laboratory to rapidly identify and develop novel biocatalysts for biofilm
dispersal activity. Overall, these research efforts will provide new unique insight into the role of PNAG in biofilm
formation and will provide tools that will impact the way that we approach treating biofilm infections.

## Key facts

- **NIH application ID:** 11036902
- **Project number:** 3R35GM147110-03S1
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Myles B Poulin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $237,866
- **Award type:** 3
- **Project period:** 2022-07-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11036902

## Citation

> US National Institutes of Health, RePORTER application 11036902, Chemical and biochemical tools to study the functions of exopolysaccharides in bacterial biofilms (3R35GM147110-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11036902. Licensed CC0.

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