Bioengineered commensals to fight S. aureus
Abstract
The occurrence and virulence of pathogens such as methicillin-resistant Staphylococcus (S.) aureus (MRSA) is rapidly increasing, with a limited number of antibiotics available or in development to treat infections. There is significant need for new therapeutics for both prevention as well as acute care. The objective of this grant is to discover and develop a new class of antimicrobials against MRSA. Different microbes secrete potent antimicrobials as a natural defense mechanism, and mining such microbes is likely an effective way to find new antibiotics. With computational tools, we can identify potential genes and pathways for their synthesis, but often we are not able to identify a chemical that is produced because these pathways are only activated under certain conditions. In our first aim, our goal is use different growth conditions and genetic tools to induce the microbes to produce these chemicals, which we will test if they inhibit S. aureus. But we need to be able to deliver these antibiotics in a very targeted way for them to have maximum effect. Biosensor organisms can detect the presence of S. aureus and respond accordingly. In our second aim, we will build such a biosensor into a non-pathogenic skin organism, S. epidermidis, and test if this biosensor can kill MRSA in the lab and also on mouse skin. The success of our grant would be powerful in creating the foundation for developing a novel, highly potent system for both preventative and acute, point-of-care treatment of MRSA and skin infections in both civilian healthcare settings and in the military. Over two million antibiotic-resistant illnesses occur each year with over 23,000 deaths. Of these, 94,000 are invasive MRSA infections associated with 19,000 deaths and nearly 60 billion dollars in health care and lost productivity costs. Staphylococcal skin infections, especially those due to MRSA, are also an important public health issue for the military; in over 30,000 military trainees, 1,203 participants developed soft-tissue infections, 316 of which were due to MRSA. In particular, we believe that our system would best be deployed in a preventative setting in the clinic for individuals at risk for hospital-acquired infections, and for military personnel before they enter these high-risk situations, thus limiting the spread of latent MRSA and preventing the development of active MRSA infections. It is likely that our platform can also be useful for acute point-of-care, with the application of novel antimicrobials that can be used in conjunction with traditional therapeutics for greater efficacy in combating MRSA infections. We expect that we will be able to test these products in a clinical trial in 18-24 months. We anticipate that the full commercialization and Food and Drug Administration approval pipeline to take 4-10 years.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810229
Entities
People
- Julia Oh
Organizations
- Jackson Laboratory
- United States Army