Analysis scripts and research data for the paper "Mechanisms of drug interactions between translation-inhibiting antibiotics"

DOI

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 observed interactions, yet fail to predict suppression. However, varying two translation bottlenecks simultaneously supports that dense traffic of ribosomes and competition for translation factors account for the previously unexplained suppression. These results highlight the importance of "continuous epistasis" in bacterial physiology.

Identifier
DOI https://doi.org/10.15479/AT:ISTA:8097
Metadata Access https://research-explorer.app.ist.ac.at/oai?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai:pub.research-explorer.app.ist.ac.at:8097
Provenance
Creator Kavcic, Bor
Publisher Institute of Science and Technology Austria
Publication Year 2020
Rights info:eu-repo/semantics/openAccess
OpenAccess true
Contact repository.manager(at)ist.ac.at
Representation
Resource Type info:eu-repo/semantics/other; doc-type:ResearchData; Text; http://purl.org/coar/resource_type/c_ddb1
Discipline Life Sciences; Medicine; Medicine and Health; Physiology