# MUC1 Biotherapeutics for Pseudomonas aeruginosa Infections

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $231,750

## Abstract

Pseudomonas aeruginosa is the single most frequently isolated Gram-negative aerobic
bacterium from hospital intensive care units (ICUs) and the most frequent bacterium
isolated from the respiratory tract of ICU patients. P. aeruginosa pneumonia and
septicemia in immunocompromised patients have directly attributable death rates
approaching 30%. P. aeruginosa is one of the most common and lethal pathogens,
notably responsible for ventilator-associated pneumonia in intubated patients, with
mortality approaching 40%. P. aeruginosa also plays a key role in the pathogenesis of
cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease, as well as
extrapulmonary diseases such as urinary tract infections, skin infections in hospital burn
units, and surgical wound and bloodstream infections. In view of its recognized clinical
impact, the increasing frequency of multi-drug-resistant P. aeruginosa is concerning as
second- and third-line antibiotics are severely limited by their increased cost and
toxicity. Thus, there is an urgent need to develop alternative therapies for P. aeruginosa
lung infections. In this R21 grant application, we propose to explore a unique and
innovative approach to treat P. aeruginosa infections using a shed MUC1 ectodomain
(MUC1-ED) decoy receptor to selectively inhibit adherence of the bacteria to host cells.
The Specific Aims are: 1) To define the mechanisms through which NEU1-mediated
MUC1-ED desialylation generates a decoy receptor that protects against P. aeruginosa
infection, and 2) To develop the recombinant MUC1-ED protein backbone as a
therapeutic agent against invasive P. aeruginosa infection. If this high-risk/high-reward
project is successful, it will result in the identification of a novel class of anti-infective
agents against P. aeruginosa. Our approach is fundamentally different from traditional
antibiotic strategies that target the microorganism itself, and is expected to be highly
complementary with direct antibacterial approaches. Finally, if this project is successful,
a similar strategy might be applied to treat other flagellated bacteria infecting mucosal
surfaces.

## Key facts

- **NIH application ID:** 9856951
- **Project number:** 5R21AI144497-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Erik P Lillehoj
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $231,750
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856951

## Citation

> US National Institutes of Health, RePORTER application 9856951, MUC1 Biotherapeutics for Pseudomonas aeruginosa Infections (5R21AI144497-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856951. Licensed CC0.

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