Stimulating T Cells to Control Antimicrobial-Resistant Lung Infections
Abstract
The goal of the project is to determine if Food and Drug Administration (FDA)-approved drugs, available at any pharmacy in the U.S., can stimulate the immune system to protect against bacteria that are resistant to antibiotics. We will examine four bacteria that are major antibiotic resistant concerns, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus (including MRSA [methicillin-resistant S. aureus]). The drugs we will test should activate a specific portion of the immune response that is known to respond to bacteria-specific molecules. Once that specific portion of the immune response is activated, it is likely to kill the bacteria and prevent and treat diseases like pneumonia. We propose to purchase de-identified blood samples from humans and add seven FDA-approved drugs, alone or two at a time, to those samples in our laboratory. The drugs are FDA-approved for diseases like bone disorders and cancers and have not yet been tested for treating bacterial infections and pneumonias. We will allow the drugs time to impact the immune response in the laboratory. We will then measure that immune response. We will conduct these experiments systematically to determine which drug or drug combination gives the strongest immune response. Once we have established which drug or drug combination works the best, we will repeat experiments with the best drugs or drug combinations, but after the drugs are added to the human blood samples, we will add one of each of the bacteria. After the drug-activated human blood has had time to activate the immune response, we will add bacteria and determine if the drug-activated human blood can kill those bacteria. These experiments will also be conducted systematically to determine which drug or drug combination kills which bacteria. Our goal is to identify the drug or drug combination that kills the most different bacteria as well as kills large numbers of bacteria. The proposed research will directly address the topic of antimicrobial resistance in that the proposed research identifies a novel/innovative target for multidrug resistance and develops a novel/innovative intervention/treatment for multidrug-resistant pathogens by repurposing FDA-approved drugs for non-infectious disease indications. It indirectly addresses acute lung injury, as the specific immune response in question has been shown to be protective in acute lung disease, namely pneumonia. Previous research in biodefense organism suggests that administering certain FDA-approved drugs stimulate a specific immune response that prevents lung damage. Administering these drugs is likely to prevent ventilator associated pneumonia, a lung injury that is secondary to many kinds of trauma.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810154
Entities
People
- Herbert Gelhaus
Organizations
- United States Army