Mucin-Based Biotherapies for Pseudomonas aeruginosa Lung Infection
Abstract
This proposal addresses Fiscal Year 2018 Peer Reviewed Medical Research Program Topic Areas "Antimicrobial Resistance" and "Respiratory Health." More than 250,000 Pseudomonas aeruginosa infections are estimated to occur annually in the U.S., with an associated healthcare cost greater than $2 billion. The widespread use of antimicrobial antibiotics has led to the emergence of difficult-to-treat, multidrug-resistant Pseudomonas aeruginosa strains, necessitating the use of less-desirable, alternative drugs that are severely limited by their decreased effectiveness and increased toxicity and costs. Therefore, alternative therapies to treat Pseudomonas aeruginosa infections are urgently needed. Based on previous research, we propose that synthetic peptide drugs derived from a naturally produced lung protein, MUC1, will offer new treatment options for patients with Pseudomonas aeruginosa lung infections. MUC1 peptide drugs will provide a novel class of Pseudomonas aeruginosa therapeutics with reduced off-target effects and enhanced effectiveness in the clinic. Because the mode of action of MUC1 peptide drugs in preventing Pseudomonas aeruginosa infection relies on inhibiting bacterial adhesion to human lung cells, rather than a direct bactericidal approach as with current antibiotics, MUC1 peptides are unlikely to spur the development of bacterial resistance. In this project, MUC1 peptides will be tested for their ability to inhibit Pseudomonas aeruginosa lung infection using both in vitro and in vivo techniques. We expect to identify at least one peptide with a high therapeutic index for treating an ongoing Pseudomonas aeruginosa infection and that is readily bioavailable and nontoxic following aerosol delivery to mouse lungs in an experimental model of Pseudomonas aeruginosa pneumonia. We envision that, once commercialized, MUC1 peptide therapeutics will be used in combination with current standard of care antibiotics to increase patient survival beyond that achieved by antibiotics alone.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 05, 2019
- Source ID
- W81XWH1910056
Entities
People
- Erik Lillehoj
Organizations
- United States Army
- University of Maryland, Baltimore