Chemical Countermeasures for Antibiotic Resistance
Abstract
The purpose of this research is to simultaneously address both multi-drug resistance and biofilm development. The overall goal of this research is therefore to identify a 2-AIT conjugate that, at submicromolar levels and in conjunction with conventional antibiotics, will: 1) disperse biofilms from both Grampositive and Gram-negative pathogens, focusing on Pseudomonas aeruginosa, methicillin resistant Staphylococcus aureus (MRSA), and MDR Acinetobacter baumannii (MDRAB); 2) re-sensitize MDR variants of these pathogens to the effects of at least one conventional, FDA-approved antibiotic; and 3) exhibit acceptable toxicological properties for use on the Wounded Warrior. Based upon this goal, the Aims of this research proposal are to: 1. Develop highly active 2-AIT derivatives based upon a current lead compound. 2. Evaluate 2-AIT derivatives for their ability to inhibit and disperse bacterial biofilms, as well as suppress antibiotic resistance. 3. Evaluate active 2-AIT derivatives for in vitro toxicity. Models will include epidermal cell toxicity, model organism toxicity (Caenorhabditis elegans), and hemolysis. 4. Evaluate active 2-AIT derivatives for in vivo activity in collaboration with COL. Craft (Director, Wound Infections/Diagnostics) and his team at Walter Reed Army Institute of Research (WRAIR). We will employ the use of three separate models, mouse puncture and pig partial thickness wound models that will evaluate the topical efficacy of the 2-AIT derivatives. We will also evaluate the 2-AIT derivatives in a rat osteomyelitis model of infection.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2012
- Accession Number
- ADA562202
Entities
People
- Christian Melander
Organizations
- North Carolina State University