# Structural Investigations of Biofilm Matrices for Novel Antibiofilm Strategies

> **NIH NIH R01** · CORNELL UNIVERSITY · 2021 · $325,211

## Abstract

Project Summary/Abstract
This project will combine molecular dynamics simulations and other types of molecular mechanics calculations
with various experimental methods to characterize the biofilms formed by opportunistic pathogen species
belonging to the Burkholderia cepacia Complex (BCC) and by Klebsiella pneumoniae. Bacterial biofilms
constitute a serious concern in infections since they confer increased resistance towards antimicrobial therapies.
In biofilms, bacteria live within a hydrated matrix composed of various macromolecules, and in particular
polysaccharides, which are primarily responsible for its formation. Understanding the details of biofilm matrix
structure can be of significant utility in designing novel strategies for treating infections. This is the main objective
of this proposal, which is a request for the continuation of a currently funded NIH study (GM123283) based on
the results acquired in this current project characterizing the structure of polysaccharides produced by species
of the BCC and K. pneumoniae. These polymers contain clusters of non-polar rhamnose residues that confer a
less polar character to the chains, suggesting the possible formation of hydrophobic juncture zones in the gel-
like structures of their biofilm matrices, and possibly constituting targets for biofilm disruption.
On the basis of the results already achieved, the following research lines will be explored both experimentally
and by computer modelling:
1) Structurally different rhamnose-rich polysaccharides produced by Burkholderia and Klebsiella will be studied
 to investigate their morphology and aggregation tendency, with the objective of modeling their biofilm matrix
architectures.
2) The interactions of matrix polysaccharides with molecules participating in quorum sensing systems will be
 studied to define the role of the matrix in cell-cell communication.
3) The possibility of weakening matrix architecture by using specific agents will be explored using three systems,
 all designed to target matrix junction zones: i) oligosaccharides containing rhamnose residues; ii) specific
 peptides which have already been found, by means of phage display procedures, to bind bacterial
 polysaccharides; iii) synthetic glycopeptides obtained binding rhamnose residues to selected peptides
 investigated in point ii). Changes in biofilm matrix morphologies will be studied by adding these test molecules
 to bacterial cultures.

## Key facts

- **NIH application ID:** 10121695
- **Project number:** 2R01GM123283-04
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** JOHN W BRADY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $325,211
- **Award type:** 2
- **Project period:** 2017-09-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121695

## Citation

> US National Institutes of Health, RePORTER application 10121695, Structural Investigations of Biofilm Matrices for Novel Antibiofilm Strategies (2R01GM123283-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10121695. Licensed CC0.

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