University of Pittsburgh researchers have identified a novel approach to combat antibiotic resistance in Gram-negative bacterial pathogens using cationic peptides. This innovative method targets the resistance mechanisms in Pseudomonas aeruginosa by requiring specific combinations of mutations for the bacteria to develop resistance. The approach leverages the restrictive evolutionary pathways of these pathogens, making them susceptible to the cationic peptide WLBU2 or PLG206 even when they are resistant to other antibiotics.
Description
The discovery provides a significant advancement in understanding and overcoming antibiotic resistance. By focusing on the genetic pathways to resistance, this method offers a targeted treatment that can prevent the evolution of resistance in P. aeruginosa and other Gram-negative priority pathogens. The identified mutations in genes such as pmrB, wspF, yfiR, wbpM, orfN, trbL, and morA represent critical targets for the application of WLBU2/PLG206.
Applications
• Drug Development
• Clinical Treatment
• Antibiotic Development
Advantages
This technology in understanding resistance mechanisms offers several advantages. Firstly, the requirement for multiple mutations to develop resistance to WLBU2/PLG206 suggests a lower probability of resistance emerging in clinical settings, making these peptides highly valuable for treating drug-resistant infections. Additionally, this research provides a detailed map of the genetic pathways involved in resistance, which can be leveraged to design combination therapies that prevent or delay the emergence of resistance. The findings also open up new avenues for developing diagnostic tools to rapidly identify bacterial strains that remain susceptible to these peptides, thereby improving the effectiveness of treatment regimens.
Invention Readiness
The research behind this discovery is supported by robust in vitro data, utilizing experimental evolution and whole-population genome sequencing to track the genetic changes leading to resistance. The team identified combinations of mutations in key genes, such as pmrB, wspF, and others, that confer resistance to WLBU2/PLG206. These findings were validated through reproducible experiments, demonstrating that such resistance is not easily attainable by the bacteria. The research is currently at an advanced stage, with published studies establishing the scientific foundation of the discovery. Ongoing work aims to further explore the potential for clinical applications.
IP Status
https://patents.google.com/patent/US20220332777A1
