Defining the mechanism of action of the nitrofuranyl piperazine HC2210 against Mycobacterium abscessus.

ABSTRACT: Mycobacterium abscessus (Mab) has intrinsic resistance to diverse classes of antibiotics, making this non-tuberculous mycobacterial (NTM) infection challenging to treat. Three nitrofuranyl piperazines-HC2209, HC2210, and HC2211-were previously reported to be active against M. tuberculosis (Mtb). Here we report that HC2210 is also active against Mab and define its mechanisms of action. HC2210 is about fivefold more potent than amikacin, is active against multidrug-resistant Mab clinical isolates, and synergizes with bedaquiline, clarithromycin, and meropenem. Isolation of resistant mutants supports that HC2210 requires cofactor F₄₂₀, although an F_420-dependent activating nitroreductase could not be identified. Additionally, resistance mutations in glycerol kinase (glpK

SUBMITTER: Eke IE 

PROVIDER: S-EPMC12167376 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature