Development of next generation antimicrobial peptides as antimicrobial therapy
Abstract
The prevalence of highly evolved, antibiotic resistant bacteria strains implies that reliance on current antibiotic therapy is no longer viable. With the lack of established treatment options against superbugs, coupled with the slow progress in new antibiotic development, there is an urgent need for antibiotic alternatives that can effectively curb the further rise of superbugs. Confronted by this urgent need, this proposal aims to study the development of efficacious peptide-based antimicrobial molecules that possess broad spectrum and rapid membrane-targeting bactericidal properties, to keep resistance development risks low. To ensure that these peptides can be readily accessible to users, this project also aims to develop a production platform that is capable of cost effectively manufacturing these peptides at industrially-viable amounts. In the first phase of this proposed study, peptide structure-activity studies to establish the correlation between peptide conformation-orientation and functionality will be conducted using biophysical tools. The findings of the structure-activity studies will elucidate the peptides’ mechanism of action and guide subsequent peptide engineering efforts to enhance antimicrobial potency and biocompatibility of selected antimicrobial peptide (AMP) candidates. Peptide stability and functionality will be evaluated in environments tailored to different antimicrobial coating and formulation applications. In the second phase of this proposed study, a peptide bioproduction route based on Picha pastoris (P. pastoris) yeast will be developed to study high cell density production of our engineered AMP. Specifically, a genetic construct that optimizes the expression and secretion of AMP within P. pastoris will be developed.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 09, 2018
- Source ID
- FA23861714083
Entities
People
- Susanna Leong
Organizations
- Air Force Office of Scientific Research
- Singapore Institute of Technology
- United States Air Force