SUMMARY OF INVENTION
Pseudomonas aeruginosa is an opportunistic bacterial pathogen that infects over 50,000 people in the US each year. It is commonly associated with hospital-acquired infections, where it infects immunocompromised patients, leading to serious illness and death. Multidrug-resistant Pseudomonas can be deadly for patients in critical care and is designated as a “serious threat” by the Centers for Disease Control and Prevention.
Despite the availability of antibiotics to treat most bacterial infections, P. aeruginosa has both intrinsic and extrinsic mechanisms of developing antibiotic resistance, making it difficult to treat such infections. Additionally, these bacteria have evolved complex communication systems called quorum sensing pathways, which control group behaviors to trigger coordinated responses. One such system is called the Pseudomonas quinolone signal (PQS) pathway. The PQS pathway controls production of virulence factors and promotes biofilm formation, and is required for full pathogenicity in several hosts. Memorial Sloan Kettering investigators have identified novel compounds that inhibit a key enzyme (PqsA) in this pathway. Current studies are focused on optimizing these compounds to improve their activity and pharmacokinetic properties, while simultaneously synthesizing and testing new analogs.
- No currently available antibiotics against this validated target
- Targeting this novel pathway can help treat pathogens that are resistant to commonly used antibiotics
With the threat of widespread antibiotic resistance, there is an urgent need for developing new and improved antibiotics. P. aeruginosa infects over 50,000 people in the US each year. Of these, 13% are multi-drug resistant, making them even harder to treat.
U.S. National Patent (10,874,686) issued in December 2020
Ji et al. (2016) Designed Small-Molecule Inhibitors of the Anthranilyl-CoA Synthetase PqsA Block Quinolone Biosynthesis in Pseudomonas aeruginosa. ACS Chemical Biology (PubMed link)
- Derek S. Tan, PhD, Laboratory Head, Chemical Biology Program, Sloan Kettering Institute; Member and Tri-Institutional Associate Professor, Memorial Sloan Kettering Cancer Center
James Delorme, PhD