[{"date_created":"2020-07-06T20:40:19Z","oa_version":"Published Version","acknowledged_ssus":[{"_id":"LifeSc"}],"date_published":"2020-07-15T00:00:00Z","file_date_updated":"2020-07-14T12:48:09Z","month":"07","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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. <a href=\"https://doi.org/10.15479/AT:ISTA:8097\">https://doi.org/10.15479/AT:ISTA:8097</a>","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, <a href=\"https://doi.org/10.15479/AT:ISTA:8097\">10.15479/AT:ISTA:8097</a>.","ama":"Kavcic B. Analysis scripts and research data for the paper “Mechanisms of drug interactions between translation-inhibiting antibiotics.” 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8097\">10.15479/AT:ISTA:8097</a>","short":"B. Kavcic, (2020).","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. <a href=\"https://doi.org/10.15479/AT:ISTA:8097\">https://doi.org/10.15479/AT:ISTA:8097</a>.","mla":"Kavcic, Bor. <i>Analysis Scripts and Research Data for the Paper “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.”</i> Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8097\">10.15479/AT:ISTA:8097</a>."},"day":"15","department":[{"_id":"GaTk"}],"article_processing_charge":"No","type":"research_data","has_accepted_license":"1","contributor":[{"orcid":"0000-0002-6699-1455","contributor_type":"research_group","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper"},{"contributor_type":"research_group","last_name":"Bollenbach","first_name":"Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87"}],"publisher":"Institute of Science and Technology Austria","file":[{"date_created":"2020-07-06T20:38:27Z","file_id":"8098","content_type":"application/zip","checksum":"5c321dbbb6d4b3c85da786fd3ebbdc98","access_level":"open_access","date_updated":"2020-07-14T12:48:09Z","relation":"main_file","file_size":255770756,"creator":"bkavcic","file_name":"natComm_2020_scripts.zip"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"doi":"10.15479/AT:ISTA:8097","keyword":["Escherichia coli","antibiotic combinations","translation","growth laws","drug interactions","bacterial physiology","translation inhibitors"],"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."}],"year":"2020","_id":"8097","title":"Analysis scripts and research data for the paper \"Mechanisms of drug interactions between translation-inhibiting antibiotics\"","oa":1,"author":[{"full_name":"Kavcic, Bor","last_name":"Kavcic","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","first_name":"Bor","orcid":"0000-0001-6041-254X"}],"status":"public","date_updated":"2024-02-21T12:40:51Z"},{"year":"2020","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."}],"keyword":["Escherichia coli","antibiotic combinations","translation","growth laws","drug interactions","bacterial physiology","translation inhibitors"],"doi":"10.15479/AT:ISTA:8930","author":[{"orcid":"0000-0001-6041-254X","full_name":"Kavcic, Bor","last_name":"Kavcic","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","first_name":"Bor"}],"oa":1,"title":"Analysis scripts and research data for the paper \"Minimal biophysical model of combined antibiotic action\"","_id":"8930","status":"public","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"8997"}]},"date_updated":"2024-02-21T12:41:42Z","date_published":"2020-12-10T00:00:00Z","oa_version":"Published Version","date_created":"2020-12-09T15:04:02Z","day":"10","department":[{"_id":"GaTk"}],"citation":{"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. <a href=\"https://doi.org/10.15479/AT:ISTA:8930\">https://doi.org/10.15479/AT:ISTA:8930</a>","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.","ama":"Kavcic B. Analysis scripts and research data for the paper “Minimal biophysical model of combined antibiotic action.” 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8930\">10.15479/AT:ISTA:8930</a>","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, <a href=\"https://doi.org/10.15479/AT:ISTA:8930\">10.15479/AT:ISTA:8930</a>.","short":"B. Kavcic, (2020).","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. <a href=\"https://doi.org/10.15479/AT:ISTA:8930\">https://doi.org/10.15479/AT:ISTA:8930</a>.","mla":"Kavcic, Bor. <i>Analysis Scripts and Research Data for the Paper “Minimal Biophysical Model of Combined Antibiotic Action.”</i> Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8930\">10.15479/AT:ISTA:8930</a>."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2020-12-09T15:00:19Z","ddc":["570"],"month":"12","contributor":[{"contributor_type":"supervisor","orcid":"0000-0002-6699-1455","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik"},{"last_name":"Bollenbach","first_name":"Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","contributor_type":"supervisor"}],"has_accepted_license":"1","type":"research_data","article_processing_charge":"No","file":[{"file_id":"8932","date_created":"2020-12-09T15:00:19Z","access_level":"open_access","checksum":"60a818edeffaa7da1ebf5f8fbea9ba18","content_type":"application/zip","success":1,"date_updated":"2020-12-09T15:00:19Z","file_name":"PLoSCompBiol2020_datarep.zip","creator":"bkavcic","relation":"main_file","file_size":315494370}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publisher":"Institute of Science and Technology Austria"}]