--- _id: '8097' abstract: - lang: eng text: '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.' acknowledged_ssus: - _id: LifeSc article_processing_charge: No author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X citation: ama: Kavcic B. Analysis scripts and research data for the paper “Mechanisms of drug interactions between translation-inhibiting antibiotics.” 2020. doi:10.15479/AT:ISTA:8097 apa: Kavcic, B. (2020). Analysis scripts and research data for the paper “Mechanisms of drug interactions between translation-inhibiting antibiotics.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8097 chicago: Kavcic, Bor. “Analysis Scripts and Research Data for the Paper ‘Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.’” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8097. ieee: B. Kavcic, “Analysis scripts and research data for the paper ‘Mechanisms of drug interactions between translation-inhibiting antibiotics.’” Institute of Science and Technology Austria, 2020. ista: Kavcic B. 2020. Analysis scripts and research data for the paper ‘Mechanisms of drug interactions between translation-inhibiting antibiotics’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:8097. mla: Kavcic, Bor. Analysis Scripts and Research Data for the Paper “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8097. short: B. Kavcic, (2020). contributor: - contributor_type: research_group first_name: Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - contributor_type: research_group first_name: Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach date_created: 2020-07-06T20:40:19Z date_published: 2020-07-15T00:00:00Z date_updated: 2024-02-21T12:40:51Z day: '15' department: - _id: GaTk doi: 10.15479/AT:ISTA:8097 file: - access_level: open_access checksum: 5c321dbbb6d4b3c85da786fd3ebbdc98 content_type: application/zip creator: bkavcic date_created: 2020-07-06T20:38:27Z date_updated: 2020-07-14T12:48:09Z file_id: '8098' file_name: natComm_2020_scripts.zip file_size: 255770756 relation: main_file file_date_updated: 2020-07-14T12:48:09Z has_accepted_license: '1' keyword: - Escherichia coli - antibiotic combinations - translation - growth laws - drug interactions - bacterial physiology - translation inhibitors month: '07' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria status: public title: Analysis scripts and research data for the paper "Mechanisms of drug interactions between translation-inhibiting antibiotics" tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '8930' abstract: - lang: eng text: Phenomenological relations such as Ohm’s or Fourier’s law have a venerable history in physics but are still scarce in biology. This situation restrains predictive theory. Here, we build on bacterial “growth laws,” which capture physiological feedback between translation and cell growth, to construct a minimal biophysical model for the combined action of ribosome-targeting antibiotics. Our model predicts drug interactions like antagonism or synergy solely from responses to individual drugs. We provide analytical results for limiting cases, which agree well with numerical results. We systematically refine the model by including direct physical interactions of different antibiotics on the ribosome. In a limiting case, our model provides a mechanistic underpinning for recent predictions of higher-order interactions that were derived using entropy maximization. We further refine the model to include the effects of antibiotics that mimic starvation and the presence of resistance genes. We describe the impact of a starvation-mimicking antibiotic on drug interactions analytically and verify it experimentally. Our extended model suggests a change in the type of drug interaction that depends on the strength of resistance, which challenges established rescaling paradigms. We experimentally show that the presence of unregulated resistance genes can lead to altered drug interaction, which agrees with the prediction of the model. While minimal, the model is readily adaptable and opens the door to predicting interactions of second and higher-order in a broad range of biological systems. article_processing_charge: No author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X citation: ama: Kavcic B. Analysis scripts and research data for the paper “Minimal biophysical model of combined antibiotic action.” 2020. doi:10.15479/AT:ISTA:8930 apa: Kavcic, B. (2020). Analysis scripts and research data for the paper “Minimal biophysical model of combined antibiotic action.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8930 chicago: Kavcic, Bor. “Analysis Scripts and Research Data for the Paper ‘Minimal Biophysical Model of Combined Antibiotic Action.’” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8930. ieee: B. Kavcic, “Analysis scripts and research data for the paper ‘Minimal biophysical model of combined antibiotic action.’” Institute of Science and Technology Austria, 2020. ista: Kavcic B. 2020. Analysis scripts and research data for the paper ‘Minimal biophysical model of combined antibiotic action’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:8930. mla: Kavcic, Bor. Analysis Scripts and Research Data for the Paper “Minimal Biophysical Model of Combined Antibiotic Action.” Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8930. short: B. Kavcic, (2020). contributor: - contributor_type: supervisor first_name: Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - contributor_type: supervisor first_name: Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach date_created: 2020-12-09T15:04:02Z date_published: 2020-12-10T00:00:00Z date_updated: 2024-02-21T12:41:42Z day: '10' ddc: - '570' department: - _id: GaTk doi: 10.15479/AT:ISTA:8930 file: - access_level: open_access checksum: 60a818edeffaa7da1ebf5f8fbea9ba18 content_type: application/zip creator: bkavcic date_created: 2020-12-09T15:00:19Z date_updated: 2020-12-09T15:00:19Z file_id: '8932' file_name: PLoSCompBiol2020_datarep.zip file_size: 315494370 relation: main_file success: 1 file_date_updated: 2020-12-09T15:00:19Z has_accepted_license: '1' keyword: - Escherichia coli - antibiotic combinations - translation - growth laws - drug interactions - bacterial physiology - translation inhibitors month: '12' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '8997' relation: used_in_publication status: public status: public title: Analysis scripts and research data for the paper "Minimal biophysical model of combined antibiotic action" tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ...