Princeton Docket # 17-3325-1
High quality medical imaging technology has been one of most important developments in clinical care and personalized medicine. Pinpointing the source and cause of disease in a patient allows targeted and optimal treatment, saving time and money. Applying this type of imaging accuracy to the identification of bacterial pathogens and infection sites is a critical unmet need. Overuse of broad-spectrum antibiotics is rapidly selecting for resistance, but the time required to biopsy and culture for species determination limits the use of targeted techniques. To allow in vivo imaging of bacterial infections, researchers at Princeton University have created a method to conjugate trackable probes to quorum-sensing (QS) molecules.
Quorum sensing is a cell-cell communication process that bacterial collectives use to regulate group behaviors such as biofilm formation and the synchronous production of virulence factors. This process involves the production, release, and population-wide detection of extracellular signal molecules called autoinducers. As these molecules are highly species specific, a trackable QS probe can be used as a diagnostic to determine both the location and the identity of a specific pathogen in many systems. These probes can be fluorescent for surface detection, or radionuclides such as PET probes for in vivo medical imaging.
This method represents a significant improvement over other infection-detection strategies. Metabolic and white blood cell labeling methods struggle to differentiate between infection and inflammation. Radiolabeled antibiotics detect infection, but cannot determine the species responsible. In addition, using labeled antibiotics can contribute to the resistance that this method seeks to avoid. Targeted and limited use of antibiotic compounds is a key part of the war against resistance, and this technology is a novel method to quickly narrow in on the most effective
• Pinpoint the location and identity of a bacterial pathogen in many systems including:
o In vivo medical imaging with radionuclide or PET probes
o In vitro medical or industrial monitoring with fluorescent probes
• Multiplex probes from different species to identify mixed populations
• Can determine species identity
• Does not use resistance-cause antibiotics
• Can also disperse biofilms, increasing the effectiveness of treatment
Kim, M. K., Zhao, A., Wang, A., Brown, Z. Z., Muir, T. W., Stone, H. A., & Bassler, B. L. (2017). Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development. Nature Microbiology, 2, 17080. https://doi.org/10.1038/nmicrobiol.2017.80
Bonnie L. Bassler, Princeton's Squibb Professor and Chair of the Department of Molecular Biology and a Howard Hughes Medical Institute investigator, is a world leader in the science of quorum sensing and the study of how bacteria communicate. Bassler is a member of the American Academy of Arts and Sciences, National Academy of Sciences, National Academy of Medicine, and the Royal Society. She has won many awards including the 2015 Shaw Prize in Life Sciences and Medicine, the 2011 Richard Lounsbery Award, and the 2002 MacArthur Foundation genius award.
Howard A. Stone is the Donald R. Dixon '69 and Elizabeth W. Dixon Professor and Chair of the Mechanical and Aerospace Engineering Department. In addition to being a member of the American Academy of Arts and Sciences, the National Academy of Engineering, and the National Academy of Sciences, Professor Stone was the winner of the inaugural Batchelor Prize sponsored by the Journal of Fluid Mechanics for the breadth and depth of his research over a 10-year period (1998-2007) and for his widely acknowledged leadership in fluid mechanics generally, as well as the APS Fluid Dynamics Prize in 2016.
Tom W. Muir, Van Zandt Williams, Jr. Class of ’65 Professor of Chemistry and Department Chair. The Muir lab combines tools of synthetic chemistry, protein biochemistry, and cell biology. Prof. Muir received the Irving Sigal Award from the Protein Society, the 2008 Blavatnik Award from the New York Academy of Sciences, and the 2013 Arthur C. Cope Scholar Award from the American Chemical Society.
Min Young Kim was a Ph.D. graduate student in the Department of Chemistry, working with Bonnie L. Bassler (Molecular Biology) and Howard A. Stone (Mechanical Engineering) at Princeton University. He earned his Ph.D. degree at Princeton University in 2017. He investigated the fundamental mechanisms underlying how bacteria colonize surfaces. He also developed physical and chemical strategies to manipulate bacterial colonization by modulating quorum sensing. Dr. Kim received the STX graduate fellowship in 2012.
Aishan Zhao is a graduate student in the Chemistry Department, working with Prof. Tom Muir. Her research specialty is using chemical biology tools to study the quorum sensing of S. aureus, including biosynthesis of autoinducing peptides, and analysis of signal detection, transduction, and response. She also developed chemical applications for applying quorum sensing signaling molecules to health-care and industrial devices. She received the McKinney Fellowship in 2013.
Intellectual Property Status
Patent protection is pending.
Princeton is seeking to identify appropriate partners for the further development and commercialization of this technology.
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