Inhibiting Mycobacterium abscessus Cell Wall Synthesis: Using a Novel Diazabicyclooctane β-Lactamase Inhibitor To Augment β-Lactam Action
Khalid M Dousa, David C. Nguyen, Sebastian G. Kurz, Magdalena A. Taracila, Christopher R. Bethel, William Schinabeck, Barry N. Kreiswirth, Sheldon T. Brown, W. Henry Boom, Richard S. Hotchkiss, Kenneth E. Remy, Frank J. Jacono, Charles L. Daley, Steven M. Holland, Alita A. Miller, Robert A. Bonomo
Abstract
Durlobactam (DUR) is a potent inhibitor of Bla Mab and provides protection of amoxicillin and imipenem against hydrolysis. DUR has intrinsic activity and forms stable acyl-enzyme complexes with Ldt Mab2 and Ldt Mab4 . The ability of DUR to protect amoxicillin and imipenem against Bla Mab and its intrinsic activity along with the dual β-lactam target redundancy can explain the rationale behind the potent activity of this combination.
Topics & Concepts
Mycobacterium abscessusPeptidoglycanMicrobiologyImipenemAntibioticsChemistryEnzymeBiologyMycobacteriumBiochemistryBacteriaAntibiotic resistanceGeneticsMycobacterium research and diagnosisAntibiotic Resistance in BacteriaTuberculosis Research and Epidemiology