Mucin-Based Biotherapies for Pseudomonas Aeruginosa Lung Infection

Abstract

The purpose of this project is to demonstrate that MUC1-ED synthetic peptides protect against Pseudomonas aeruginosa lung infection using both in vitro and in vivo model systems. Formonths 1-12 of the project, studies were conducted demonstrating that MUC1-ED 20-, 40-, 60-,80-, and 100-mer peptides 1) bound to P. aeruginosa and its flagella; 2) inhibited P.aeruginosa and flagella binding to human lung cells, and bacterial motility; 3) were not cytotoxic to lung cells; 4) did not affect lung cell barrier formation; 5) exhibited no damage to mouse lung, liver or kidney; and 6) displayed appropriate lung bioavailability in vivo. For months 13-42, studies were performed demonstrating that 1) all peptides exhibited appropriate pharmacokinetic parameters in vivo; and 2) the 80-mer and 100-mer MUC1-ED peptides reduced lung infection and inflammation, and improved survival, when administered to mice simultaneously with, prior to, or following sublethal or lethal infection with laboratory or clinical strains of P. aeruginosa, compared with scrambled control peptides.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2022
Accession Number
AD1190882

Entities

People

  • Erik P. Lillehoj

Organizations

  • University of Maryland, Baltimore

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Adhesion
  • Amino Acids
  • Anti-Bacterial Agents
  • Bacteria
  • Biomedical Research
  • Cells
  • Cellular Structures
  • Covid-19
  • Cytokines
  • Electronic Mail
  • Epithelial Cells
  • Fluorescence
  • Histopathology
  • Infection
  • Inflammation
  • Inhibition
  • Lethal Dosage
  • Maryland
  • Materials
  • Medical Personnel
  • Peptides
  • Proteins
  • Survival
  • Therapy
  • Toxicity

Fields of Study

  • Biology
  • Medicine

Readers

  • Immunology and Pathology
  • Microbial Pathology
  • Molecular Genetics