Antibacterial Peptide Development and Non-GLP In Vivo Demonstration of Activity and Efficacy Against MDR Biofilm-Forming Wound Pathogens (ESKAPE)
Abstract
This project seeks to develop a new approach to treatment of multidrug-resistant bacterial biofilm-mediated infection of wounds, especially combat wounds, such as burn and blast wounds. We have invented in our previous DTRA-funded work two small peptides, which are short chains of protein, that are able to kill the most common bacteria that infects these wounds, as well as they can promote clearance of the wound and wound healing. Both peptides showed activity against the bacteria that commonly cause wound infections, including Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter baumannii. Thus, the rationale for this study is based on our laboratory-based findings of these two peptides’ activities and to begin the development of these two lead candidates in advanced testing that will establish which of these peptides is the best one to take forward into full preclinical studies and further development. The scientific objective of the study is to validate the laboratory-discovered activities of these peptides against the organisms that most often cause wound infections and their biofilms by testing the peptides in a variety of performance-gated tasks, leading up to a full study of treating infected wounds in pigs, which are a close model for human wounds. The FY20 JWMRP Focus Area addressed in this project is Military Infectious Diseases Research Program (MIDRP) Focus Area (2):” therapeutic measures for infectious diseases, including ..novel medical countermeasures and innovative treatment approaches for multidrug-resistant organisms in combat wound infections and against pathogenic bacterial biofilm formation ...”. The long-term military benefits of the proposed project are to improve the healing of combat-wound infections and to speed up the military Service Member s ability to return to Service through this improved healing. In the short term, the military benefit of the proposed project is to have a new approach and a new class of compounds in antimicrobial peptides in the medical countermeasures development pipeline to help ensure success in combatting multidrug-resistant organisms in combat wound infections. This work will also benefit Veterans, military family members, and the American public through its application to chronic, non-healing infected wounds such as those seen in diabetes patients. The incidence of diabetes among Veterans, military family members, and the American public continues to rise, and the number of patients with chronically infected, non-healing wounds that are mediated by the same organisms and their biofilms. The long-term applicability of this research is to treat military Service Members, Veterans, military family members, and the American public who have wounds infected by these multidrug-resistant and biofilm-forming organisms, which makes the wounds very difficult to treat and heal. The potential clinical application of the peptides is as a topical treatment for infected wounds, which will help to clear the bacteria, prevent the biofilm formation, and promote wound healing in those patients. Although highly promising in laboratory-based studies, additional preclinical and safety studies need to be done before these peptides could be considered for patient trials, perhaps 5 years. Research such as is proposed here is critical to advance these potential new treatments sufficiently to the next step (in 3 years) so that preparations for such studies can be completed. The study proposed is critical to answer the outstanding unanswered questions about these peptides, especially with regards to their pharmacokinetics, to propel them forward into preclinical testing and soon after that, potentially treating infected patient wounds.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110214
Entities
People
- Monique van Hoek
Organizations
- George Mason University
- United States Army