Abstract

Nosocomial infections are the fourth leading cause of death in the U.S. with >2 million cases annually (or ~10% of American hospital patients). Biofilm infections constitute a number of clinical challenges, including diseases involving uncultivable species, chronic inflammation, impaired wound healing, rapidly generated multiple drug resistant (MDR) strains, and the spread of infectious emboli. This immune engineering approach to preventing medical device-based infections will be developed for two model MDR bacterial systems: Staphylococcus aureus (SA) (as seen on cardio-vascular devices and MRSA infections) and Pseudomonas aeruginosa (PA) (representative carbapenem-resistant Enterobacteriaceae - CRE; as seen on ventillators, endotracheal devices, catheters). Model biomaterial implants will release synthetic opsonins; bi-specific fusion complexes (BiFCs) designed to bind together invading bacteria with neutrophils and/or macrophages (M) while stimulating phagocytosis.

Public Health Relevance

This immune engineering approach to preventing infections will be developed for two model bacterial systems: Staphylococcus aureus (SA) (as seen on cardio-vascular devices and MRSA infections) and Pseudomonas aeruginosa (PA) (representative carbapenem-resistant Enterobacteriaceae - CRE). In a non-antibiotic approach to prevent biomedical implant based infections, porous templated scaffolds (PTS) will release synthetic opsonins; bi-specific fusion complexes (BiFCs) designed to bind together invading bacteria with neutrophils and/or macrophages (M) while stimulating phagocytosis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI132355-02
Application #
9528454
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Xu, Zuoyu
Project Start
2017-07-14
Project End
2019-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Bleem, Alissa; Christiansen, Gunna; Madsen, Daniel J et al. (2018) Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms. J Mol Biol 430:3751-3763
Maris, Nathan L; Shea, Dylan; Bleem, Alissa et al. (2018) Chemical and Physical Variability in Structural Isomers of an l/d ?-Sheet Peptide Designed To Inhibit Amyloidogenesis. Biochemistry 57:507-510
Bleem, Alissa; Francisco, Robyn; Bryers, James D et al. (2017) Designed ?-sheet peptides suppress amyloid formation in Staphylococcus aureus biofilms. NPJ Biofilms Microbiomes 3:16
Katzenmeyer, Kristy N; Szott, Luisa M; Bryers, James D (2017) Artificial opsonin enhances bacterial phagocytosis, oxidative burst and chemokine production by human neutrophils. Pathog Dis 75: