Structure-function comparison of Arbekacin with other aminoglycosides elucidates its higher potency as bacterial translation inhibitor.

ABSTRACT: Aminoglycoside antibiotics are well-known inhibitors of bacterial protein synthesis, which act mainly by inhibiting ribosomal translocation and inducing miscoding errors. Arbekacin (ABK) is a semisynthetic aminoglycoside that was developed by adding a 3-amino-2-hydroxybutyric (AHB) moiety to the 2-deoxystreptamine (2-DOS) ring of dibekacin for counteracting the problem of enzyme-mediated resistance of aminoglycosides. Here, we have systematically compared the inhibition efficacy of ABK with other aminoglycosides by in vivo MIC determination and in vitro fast-kinetics based translocation and termination assays complemented with a high-resolution cryo-EM structure. ABK presents significantly lower MIC₅₀ value compared to its parent antibiotics kanamycin and dibekacin. Consistent w

SUBMITTER: Majumdar S 

PROVIDER: S-EPMC12104382 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature