Description:
Princeton Docket # 15-3090
Researchers in the Department of Molecular Biology at Princeton University and the School of Medicine at Dartmouth College have identified a novel strategy for inhibiting the pathogenesis of the human pathogen Pseudomonas aeruginosa by regulating its virulence factors upon surface contact instead of inhibiting its growth. P. aeruginosa is a major cause of hospital-acquired infections, burn infections, and cystic fibrosis infections. The discovered mechanosensitive pathway is conserved in other pathogens, allowing this strategy to be exploited for developing unique antibiotics to combat multiple types of bacterial infections. The PilY1 protein has been identified as a key mechanosensor required to sense surface contact, with a mutation able to lock bacteria into a constitutively-virulent state. Preliminary results indicate that this novel antibiotic strategy may be less susceptible to the rise of resistance than traditional antibiotic approaches. The rise of antibiotic resistance is a critical international public health problem, with a substantial commercial demand for developing new antibiotic drugs and strategies to combat infections.
Applications:
• Identification of small molecules to target surface-sensitive virulence regulation
• Screen for inhibitors of surface-induced virulence
• Commercialization of new antibiotics
Advantages:
• New way to inhibit pathogenesis
• Less resistance-prone than traditional antibiotic strategies
• Not actively selecting for rise of antibiotic resistance
• Non-resistant bacteria able to successfully compete with resistant bacteria
Keywords
Antibiotic, antibiotic resistance, pathogenicity, Pseudomonas aeruginosa, public health, drug development, infection, virulence, mechanosensation, host detection, contact regulation
Related Publications
Siryaporn, A., Kuchma, S.L., O’Toole, G.A., and Gitai, Z. Surface attachment induces Pseudomonas aeruginosa virulence. Proceedings of the National Academy of Sciences, 2014. 111(47): pages 16860-16855.
Inventors
Albert Siryaporn, Ph.D., Zemer Gitai, Ph.D., Sherry Kuchma, Ph.D, and George O’Toole, Ph.D.
Faculty Inventor
Zemer Gitai, Associate Professor of Molecular Biology and Director of Graduate Studies, Department of Molecular Biology
Dr. Gitai's research focuses on the cell biology of bacteria. His lab studies how cells self-organize across spatial scales, using quantitative, molecular, and engineering approaches to understand to understand problems such as cell shape formation, cytoskeletal function, metabolic organization, and community structure. Dr. Gitai has published over 40 original articles in leading journals, including Cell, Molecular Cell, Nature Cell Biology, and PNAS. His work discovered new components of the bacterial cytoskeleton, new functions for bacterial polymers in metabolism, compartmentalization, and chromosome dynamics, and established the importance of protein assembly for unexpected processes like metabolism and pathogenesis. Dr. Gitai's achievements have been recognized by many prestigious awards, including the NIH New Innovator Award, the Beckman Young Investigator Award, and the HFSP Young Investigator Award.
Dr. Gitai graduated with a bachelor's degree from MIT in 1996. After completing his graduate studies at UCSF in 2002, Dr. Gitai became a postdoc in the lab of Dr. Lucy Shapiro at Stanford University, where he pioneered the study of the MreB actin-like cytoskeleton in Caulobacter crescentus. Dr. Gitai joined the faculty of Princeton University as an Assistant Professor of Molecular Biology in 2005. He was promoted to Associate Professor with tenure in 2012.
Intellectual Property and Licensing Status
Patent applications are pending. Princeton is seeking industrial collaborators for further development and commercialization of this technology.
Contact
Laurie Tzodikov
Princeton University Office of Technology Licensing • (609) 258-7256• tzodikov@princeton.edu
Xin (Shane) Peng
Princeton University Office of Technology Licensing • (609) 258-5579 xinp@princeton.edu