A. James Link: Lasso-shaped antibiotic for the treatment of lung infections

Sept. 10, 2019

A new antibiotic compound with an unusual shape is on track to treat deadly drug-resistant lung infections that are commonly associated with cystic fibrosis. The antibiotic is a type of "lasso peptide," a short protein segment named for its resemblance to a loop of rope. The newly developed antibiotic, dubbed ubonodin, selectively kills bacteria of the genus Burkholderia, which includes many members that are resistant to conventional antibiotics.

Developed by A. James Link, professor of chemical and biological engineering, and graduate student Wai Ling Cheung-Lee, ubodonin's distinctive shape makes it highly stable in both dissolved and dry forms across a range of temperatures. The molecule targets Burkholderia by stopping cell replication through the inhibition of RNA polymerase. The molecule is highly specific against Burkholderia strains, and this narrow-spectrum activity is advantageous because the molecule does not kill off beneficial bacteria.

The team has demonstrated the ability to produce ubonodin by introducing a novel DNA sequence into E. coli. Having shown that the molecule can kill Burkholderia cepacia, which causes lung infection, the team is now working on ways to engineer the molecule to target other pathogenic Burkholderia strains.

Team members: Wai Ling Cheung-Lee, Ph.D. 2019; Chuhan Zong, Ph.D. 2018; Madison Parry, Class of 2018

Collaborators: At the Rockefeller University, Seth Darst, the Jack Fishman Professor of Molecular Biology, and graduate student Alexis Jaramillo Cartagena; Nancy Connell, professor in the Department of Environmental Health and Engineering at the Johns Hopkins Bloomberg School of Public Health; and Riccardo Russo, research teaching specialist at Rutgers New Jersey Medical school

Development Status: Patent protection is pending. Princeton is seeking outside interest for the further development of this opportunity.

Funding: National Institutes of Health