Penicillin-resistant bacteria pose a serious threat to human welfare. This project will generate new products designed to defeat resistant microorganisms. The most prevalent cause of bacterial resistance involves the destruction of the antibiotic with the enzyme B-lactamase. There are more than 255 known B-lactamases, which have been grouped into four classes: A through D. Historically, class A has been the most clinically important. However, the incidence of class C-mediated infections has increased dramatically in the past decade. Often such resistant infections can be defeated through the co-administration of an antibiotic and a B-lactamase inhibitor. However, current commercial B-lactamase inhibitors are effective only against class A enzymes. We have now identified and patented lead compounds which are simultaneously effective against both class A and class C B-lactamases. This project will develop those leads into viable commercial products. Collaborations with a number of academic researchers and pharmaceutical companies are in place, allowing access to representative B-lactamases as well as microbiological evaluations of these inhibitors. The objective is to develop products which have a broader spectrum than commercial antibiotic/inhibitor combinations. This will include either better overall activity or better activity against a subclass of clinically important organisms not targeted by current commercial products. PROPOSED COMMERCIAL APPLICATION: These inhibitors can be combined with the commercial beta-lactam antibiotic to broaden the spectrum of the antibiotic.
