The Effect of Novel Biofilm Inhibitors on Antibiotic Resistance in E. coli
Abstract
Each year, approximately 35 million adults receive inpatient care in U.S. hospitals. More than half of the patient-days spent in hospitals involve treatment with invasive medical devices. All of these patients are at risk for healthcare-associated infections, the most common adverse event in healthcare delivery worldwide and a significant contributor to mortality and financial losses. In the United States in 2014, approximately 1 in 25 patients contracted an infection during the course of hospitalization, and the frequency of such infections in developing countries is expected to be at least three times higher than that in the United States. Pneumonia and surgical site infections are the most common, followed by gastrointestinal infection, urinary tract infection, and primary bloodstream infection. A variety of bacteria are implicated in these infections, and their distribution is dependent on the site of colonization. For example, Staphylococcus aureus dominates surgical site infections, Pseudomonas aeruginosa is a common culprit in pneumonia, and Escherichia coli tends to thrive in urinary tract infections. The World Health Organization released its ?Priority Pathogens List? in February 2017 to guide research and development of new antibiotics, and all three of the ?Priority 1 ? Critical? bacteria on this list are classified as gram-negative. E. coli has developed significant resistance to multiple carbapenem antibiotics in recent years, and well-established biofilm forms with the ability to produce extracellular amyloid fibrils. These fibrils act as scaffolding for bacterial biofilms, which help the bacteria evade the host immune response and serve as a barrier preventing access of antibiotics to the bacterial cells. In addition, E. coli is a prevalent multidrug-resistant pathogen associated with trauma-related injuries of military personnel. This proposal aims to inhibit biofilm formation in E. coli with novel peptide-based inhibitors to improve antibiotic efficacy and bacterial death.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 05, 2019
- Source ID
- W81XWH1910050
Entities
People
- Valerie Daggett
Organizations
- United States Army
- University of Washington