Insights into the l,d-Transpeptidases and d,d-Carboxypeptidase of Mycobacterium abscessus: Ceftaroline, Imipenem, and Novel Diazabicyclooctane Inhibitors.

ABSTRACT: Mycobacterium abscessus is a highly drug-resistant nontuberculous mycobacterium (NTM). Efforts to discover new treatments for M. abscessus infections are accelerating, with a focus on cell wall synthesis proteins (M. abscessus l,d-transpeptidases 1 to 5 [Ldt_Mab1 to Ldt_Mab5] and d,d-carboxypeptidase) that are targeted by β-lactam antibiotics. A challenge to this approach is the presence of chromosomally encoded β-lactamase (Bla_Mab). Using a mechanism-based approach, we found that a novel ceftaroline-imipenem combination effectively lowered the MICs of M. abscessus isolates (MIC₅₀ ≤ 0.25 μg/ml; MIC₉₀ ≤ 0.5 μg/ml). Combining ceftaroline and imipenem with a β-lactamase inhibitor, i.e., relebactam or avibactam, d

SUBMITTER: Dousa KM 

PROVIDER: S-EPMC7526840 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature