# Phage extracellular polysaccharide depolymerases to combat Pseudomonas aeruginosa biofilms

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2021 · $195,000

## Abstract

Project Summary/Abstract
The aerobic Gram-negative bacterium Pseudomonas aeruginosa is one of the most important and dangerous
microbes inhabiting the hospital environment. It is able to adapt to and thrive in many ecological niches, from
water and soil environments to plant and animal tissues. P. aeruginosa possesses a wide array of virulence
factors that not only cause extensive tissue damage but also interfere with the immune defenses. During
chronic infections, as can be present in the lungs of cystic fibrosis patients or in wound infections, populations
of P. aeruginosa undergo characteristic evolutionary adaptations, including transition from planktonic to biofilm
forms. Biofilms are structured, multicellular communities embedded in self-produced polymer matrix and play
important roles in bacterial antibiotic-resistance evolution and infection antibiotic tolerance. In 2017, multidrug-
resistant P. aeruginosa caused an estimated 32,600 infections among hospitalized patients and 2,700 deaths
only in the U.S., adding roughly $767 million annually to the cost of medical treatments. New antibacterial and
anti-biofilm agents and approaches therefore are urgently needed to better control or outright cure P.
aeruginosa infections. Bacteriophages have co-evolved with bacteria for three billion years and highly efficient
and specific antibacterial mechanisms have emerged, granting them unique advantages to kill bacteria. As
anti-biofilm agents, these viruses in particular can encode extracellular polysaccharide depolymerases (EPDs)
that they use to degrade bacterial polymers important for biofilm production and virulence. Phage EPDs can
cleave bacterial extracellular polysaccharides either associated with the cell surface (LPS or capsule
polysaccharides) or making up biofilm matrix, allowing virions to tunnel into bacterial biofilms to bacterial cell
surfaces. These phage enzymes display a great diversity in substrate specificity and can be identified by the
appearance of a constantly increasing halo zone around the phage plaques, the latter as a result of enzymatic
degradation of bacterial extracellular polysaccharides that occurs even without phage infection. Knowledge of
phage EPDs, particularly of P. aeruginosa, is currently somewhat limited, however. Only relatively few EPD
genes have been characterized that target P. aeruginosa strains. It further is unknown to what extent EPD
activity is required for the phage infection process or how possible variations in the amount and density of the
bacterial extracellular polysaccharides influence this process. Not much is known as well about the structure,
substrate binding, and cleaving domains of anti-P. aeruginosa EPDs. Our goal in the proposed project
therefore is the identification and characterization of multiple, diverse, anti-P. aeruginosa EPDs and
determination of their impact on diverse Pa biofilms and virulence. The use of bacteriophage recombinantly
manufactured proteins offers a great opport...

## Key facts

- **NIH application ID:** 10109763
- **Project number:** 1R21AI156304-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** STEPHEN T ABEDON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $195,000
- **Award type:** 1
- **Project period:** 2020-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10109763

## Citation

> US National Institutes of Health, RePORTER application 10109763, Phage extracellular polysaccharide depolymerases to combat Pseudomonas aeruginosa biofilms (1R21AI156304-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10109763. Licensed CC0.

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