Selective trihydroxyazepane NagZ inhibitors increase sensitivity of Pseudomonas aeruginosa to beta-lactams
Résumé
AmpC beta-lactamase confers resistance to b-lactam antibiotics in many Gram negative bacteria. Inducible expression of AmpC requires an N-acetylglucosaminidase termed NagZ. Here we describe the synthesis and characterization of hydroxyazepane inhibitors of NagZ. We find that these inhibitors enhance the susceptibility of clinically relevant Pseudomonas aeruginosa to beta-lactams.