Antibiotic Use of Ubonodin and its Derivatives Against Burkholderia Infections
Researchers at Princeton University have developed a novel compound that potently kills members of the Burkholderia genus, a notorious family of bacteria that includes multiple human and plant pathogens. Many Burkholderia are resistant to conventional antibiotics, so this compound represents a new strategy for applications in healthcare and biocontrol. The compound is robust, and exhibits thermal stability and shelf stability in both dissolved and dry forms.
• Ubonodin and its derivatives can be used as antibiotics for the treatment of Burkholderia cepacia complex (Bcc) infections such as those causing forms of pneumonia in cystic fibrosis (CF) patients
• Ubonodin can be used in biocontrol as it exhibits activity against multiple strains of Burkholderia mallei
• Potent antibiotic activity against Bcc strains, which are naturally resistant to many current antibiotics on the market
• Ubonodin has the potential to be delivered directly to the lungs as part of prophylactic antibiotic treatment for CF patients
• Ubonodin is a targeted antibiotic, leaving the healthy microbiome unaffected
Burkholderia is a genus of Gram-negative Proteobacteria comprised of resilient and ubiquitous bacteria that are mainly environmental saprophytes. Many of its members are opportunistic pathogens that can cause fatal diseases. Burkholderia mallei and Burkholderia pseudomallei, are classified as Tier 1 Select Agents by the US Federal Select Agent Program, causing glanders in animals and melioidosis in humans, respectively. The Burkholderia cepacia complex (Bcc) consists of more than 20 closely related species of which many are opportunistic plant and human pathogens. Bcc members are especially dangerous to patients with an underlying lung disease, such as those with cystic fibrosis, causing deadly pneumonia. Bcc infections are difficult to treat due to their innate resistance to many antibiotics, their ability to persist even with aggressive antibiotic treatment, and their ability to acquire resistance to these antibiotics.
Stage of Development
The researchers have confirmed antimicrobial activity in vitro. They can readily supply mg quantities of highly-purified ubonodin for testing.
Discovery of Ubonodin, An Antimicrobial Lasso Peptide Active Against Members of the Burkholderia Cepacia Complex, Wai Ling Cheung-Lee, Madison E. Parry, Chuhan Zong, Alexis Jaramillo Cartagena, Seth A. Darst, Nancy D. Connell, Riccardo Russo, and A. James Link, ChemBioChem, 2020, 21, 1335-1340. DOI: 10.1002/cbic.201900707
A. James Link joined the Princeton faculty in 2007 and is currently a full professor of chemical and biological engineering with appointments in the departments of chemistry and molecular biology. His lab is among the world leaders in research into lasso peptides, a class of natural products with rich bioactivities. Work in the Link lab has been recognized with major national awards, such as Sloan Fellowship in Chemistry.
Wai Ling Cheung-Lee obtained her BSE (2010) and PhD (2019) from Princeton University. In between her stints at Princeton, she worked in the renewable energy industry and the biopharma industry. She currently works for Merck & Co.
Intellectual Property Status
Patent protection is pending. Princeton University is currently looking for Industry collaborators to further develop and commercialize this technology.
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