Richard Taylor | March 11, 2017
For the first time, the World Health Organization (WHO) published a list of “priority pathogens” which constitute a current and extreme threat to human health. WHO is seeking to promote new efforts in the discovery and development of new antibiotics to address a growing threat of antibiotic resistance.
Research encompassing the fundamental mechanism of antibiotic resistance and bacterial biofilms as well as the discovery of new antibiotics and the development of new tools to aid in their discovery have a rich history at the University of Notre Dame and researchers within the Warren Family Center for Drug Discovery & Development.
Shahriar Mobashery’s team recently published research on the regulation of the peptidoglycan protective layer of Gram-negative bacteria such as Pseudomonas aeruginosa. In collaboration with Mayland Chang, Mobashery also discovered two new classes of antibacterials, the oxadiazoles and quinazolinones. The oxadiazoles are active against Gram-positive bacteria, are bactericidal, have efficacy in mouse models of infection, have excellent pharmacokinetic properties, including oral bioavailability, and display a long post-antibiotic effect. The quinazolinones show efficacy in mouse models of methicillin-resistant Staphylococcus aureus (MRSA) infection, and have an unprecedented mechanism of action, binding to the allosteric site of penicillin-binding protein 2a and triggering conformational changes that lead to opening of the active site, allowing access to the site by β-lactam antibiotics, which normally cannot gain access because of the closed conformation of the active site.