Mechanisms of drug interactions between translation-inhibiting antibiotics.

ABSTRACT: Antibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we explain these interactions by "translation bottlenecks": points in the translation cycle where antibiotics block ribosomal progression. To elucidate the underlying mechanisms of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using inducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks causes these interactions. We further show that growth laws, combined with drug uptake and binding kinetics, enable the direct prediction of a large fraction of

SUBMITTER: Kavcic B 

PROVIDER: S-EPMC7421507 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature