OU receives $5.7 million NIH grantPublished: Wednesday, May 9, 2018 By: Journal Record Staff Source: The Journal Record
University of Oklahoma professors Helen Zgurskaya and Valentin Rybenkov and their colleagues are addressing the need for new antibiotics that can fight infections caused by the multi-drug resistant bacterium Pseudomonas aeruginosa, considered an urgent threat by the Centers for Disease Control and Prevention.
The OU team received a five-year, $5.7 million grant from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, to develop new, more effective approaches against Gram-negative bacteria that are protected by multi-drug efflux pumps and low-permeability membranes.
“The challenge is to develop approaches that will enable antibiotic penetration across non-specific permeability barriers of Gram-negative bacteria, which poses an urgent and serious threat to public health,” Zgurskaya said in a press release. “In response, we are developing a new technology for optimization of efflux avoidance and inhibition in clinical and investigational antibacterial agents that will be effective against Gram-negative bacteria.”bacterium Pseudomonas aeruginosa, considered an urgent threat by the Centers for Disease Control and Prevention.
Zgurskaya, an expert in bacterial efflux pumps and antibiotic resistance, and Rybenkov, an expert in kinetic modeling, are working with Paola Ruggerone, University of Cagliari, Italy; Gnana Gnanakaran, Los Alamos National Laboratory; John Walker, Saint Louis University School of Medicine; Basilea Pharmaceutica, Switzerland and Medicines Company, San Diego, California.
“We have to understand the difference between the antibiotic and the efflux pump inhibitor, so we can combine the properties of both to get compounds inside the cell and kill the bacteria,” Zgurskaya in the press release. “OU will do the experimental and kinetic analysis of the data; the University of Cagliari will compute efflux pump interactions with antibiotics and inhibitors; Los Alamos National Laboratory will determine how inhibitors and substrates permeate the membrane; and Saint Louis School of Medicine will synthesize new molecules with the new properties. Basilea Pharmaceutical and the Medicines Company can then test this new approach in development of efflux pump inhibitors.”