{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:50:40Z","timestamp":1789602640228,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pbio.2004356","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T00:00:00Z","timestamp":1525910400000}}],"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T00:00:00Z","timestamp":1525046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"DOI":"10.1371\/journal.pbio.2004356","type":"journal-article","created":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T17:35:08Z","timestamp":1525109708000},"page":"e2004356","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":98,"title":["Antibiotic combination efficacy (ACE) networks for a Pseudomonas aeruginosa model"],"prefix":"10.1371","volume":"16","author":[{"given":"Camilo","family":"Barbosa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Beardmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1413-913X","authenticated-orcid":true,"given":"Hinrich","family":"Schulenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunther","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2018,4,30]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1126\/science.257.5073.1064","article-title":"The Crisis in Antibiotic Resistance","volume":"257","author":"HC Neu","year":"1992","journal-title":"Science"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1128\/MMBR.00016-10","article-title":"Origins and Evolution of Antibiotic Resistance","volume":"74","author":"J Davies","year":"2010","journal-title":"Microbiol Mol Biol Rev"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1038\/509S2a","article-title":"Antibiotic resistance: An infectious arms race","volume":"509","author":"K Hede","year":"2014","journal-title":"Nature"},{"key":"ref4","first-page":"5437","article-title":"Emergence of extensively drug-resistant and pandrug-resistant Gram-negative bacilli in Europe","volume":"13","author":"M Souli","year":"2008","journal-title":"Euro Surveill Bull Eur Sur Mal Transm Eur Commun Dis Bull"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1016\/S0140-6736(10)60410-2","article-title":"Multidrug-resistant and extensively drug-resistant tuberculosis: a threat to global control of tuberculosis","volume":"375","author":"NR Gandhi","year":"2010","journal-title":"The Lancet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/ja.2010.62","article-title":"Antibiotic discovery in the twenty-first century: current trends and future perspectives","volume":"63","author":"S Donadio","year":"2010","journal-title":"J Antibiot (Tokyo)"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1086\/652237","article-title":"The 10 \u00d7 \u201820 Initiative: Pursuing a Global Commitment to Develop 10 New Antibacterial Drugs by 2020","volume":"50","year":"2010","journal-title":"Clin Infect Dis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/472032a","article-title":"Fix the antibiotics pipeline","volume":"472","author":"MA Cooper","year":"2011","journal-title":"Nature"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nrd3975","article-title":"Platforms for antibiotic discovery","volume":"12","author":"K Lewis","year":"2013","journal-title":"Nat Rev Drug Discov"},{"key":"ref10","article-title":"A systematic review and critical assessment of incentive strategies for discovery and development of novel antibiotics","author":"MJ Renwick","year":"2015","journal-title":"J Antibiot (Tokyo)"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"aad3292","DOI":"10.1126\/science.aad3292","article-title":"Multidrug evolutionary strategies to reverse antibiotic resistance","volume":"351","author":"M Baym","year":"2016","journal-title":"Science"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nrg3351","article-title":"Understanding, predicting and manipulating the genotypic evolution of antibiotic resistance","volume":"14","author":"AC Palmer","year":"2013","journal-title":"Nat Rev Genet"},{"key":"ref13"},{"key":"ref14","unstructured":"WHO | Global tuberculosis report 2014. In: WHO [Internet]. [cited 14 Oct 2015]. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.who.int\/tb\/publications\/global_report\/en\/\" xlink:type=\"simple\">http:\/\/www.who.int\/tb\/publications\/global_report\/en\/<\/ext-link>"},{"key":"ref15"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"13977","DOI":"10.1073\/pnas.0805965105","article-title":"Accelerated evolution of resistance in multidrug environments","volume":"105","author":"M Hegreness","year":"2008","journal-title":"Proc Natl Acad Sci"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"e1001540","DOI":"10.1371\/journal.pbio.1001540","article-title":"When the Most Potent Combination of Antibiotics Selects for the Greatest Bacterial Load: The Smile-Frown Transition","volume":"11","author":"R Pena-Miller","year":"2013","journal-title":"PLoS Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.drup.2014.02.002","article-title":"Experimental evolution as an efficient tool to dissect adaptive paths to antibiotic resistance","volume":"16","author":"G Jansen","year":"2013","journal-title":"Drug Resist Updat"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1128\/JB.64.4.489-499.1952","article-title":"GENETIC STUDIES ON MICROBIAL CROSS RESISTANCE TO TOXIC AGENTS I","volume":"64","author":"W Szybalski","year":"1952","journal-title":"J Bacteriol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"204ra132","DOI":"10.1126\/scitranslmed.3006609","article-title":"Use of Collateral Sensitivity Networks to Design Drug Cycling Protocols That Avoid Resistance Development","volume":"5","author":"L Imamovic","year":"2013","journal-title":"Sci Transl Med"},{"key":"ref21","doi-asserted-by":"crossref","DOI":"10.1038\/msb.2013.57","article-title":"Bacterial evolution of antibiotic hypersensitivity","volume":"9","author":"V L\u00e1z\u00e1r","year":"2013","journal-title":"Mol Syst Biol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"14494","DOI":"10.1073\/pnas.1409800111","article-title":"Alternating antibiotic treatments constrain evolutionary paths to multidrug resistance","volume":"111","author":"S Kim","year":"2014","journal-title":"Proc Natl Acad Sci"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/nature05685","article-title":"Antibiotic interactions that select against resistance","volume":"446","author":"R Chait","year":"2007","journal-title":"Nature"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"14918","DOI":"10.1073\/pnas.0800944105","article-title":"Drug interactions modulate the potential for evolution of resistance","volume":"105","author":"J-B Michel","year":"2008","journal-title":"Proc Natl Acad Sci"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"e1000796","DOI":"10.1371\/journal.pcbi.1000796","article-title":"Optimal Drug Synergy in Antimicrobial Treatments","volume":"6","author":"JP Torella","year":"2010","journal-title":"PLoS Comput Biol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/ng1755","article-title":"Functional classification of drugs by properties of their pairwise interactions","volume":"38","author":"P Yeh","year":"2006","journal-title":"Nat Genet"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/jac\/dkp201","article-title":"Update on the treatment of Pseudomonas aeruginosa pneumonia","volume":"64","author":"AAE Solh","year":"2009","journal-title":"J Antimicrob Chemother"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1128\/AAC.47.9.2756-2764.2003","article-title":"Effectiveness of Combination Antimicrobial Therapy for Pseudomonas aeruginosa Bacteremia","volume":"47","author":"E Chamot","year":"2003","journal-title":"Antimicrob Agents Chemother"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1128\/CMR.05041-11","article-title":"Combination Therapy for Treatment of Infections with Gram-Negative Bacteria","volume":"25","author":"PD Tamma","year":"2012","journal-title":"Clin Microbiol Rev"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1093\/molbev\/msx158","article-title":"Alternative Evolutionary Paths to Bacterial Antibiotic Resistance Cause Distinct Collateral Effects","volume":"34","author":"C Barbosa","year":"2017","journal-title":"Mol Biol Evol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nbt0106-51","article-title":"Inference in Bayesian networks","volume":"24","author":"CJ Needham","year":"2006","journal-title":"Nat Biotechnol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"e129","DOI":"10.1371\/journal.pcbi.0030129","article-title":"A Primer on Learning in Bayesian Networks for Computational Biology","volume":"3","author":"CJ Needham","year":"2007","journal-title":"PLOS Comput Biol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1126\/science.1094068","article-title":"Inferring Cellular Networks Using Probabilistic Graphical Models","volume":"303","author":"N Friedman","year":"2004","journal-title":"Science"},{"key":"ref34","article-title":"The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy","author":"AF Read","year":"2011","journal-title":"Proc Natl Acad Sci"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"e1003578","DOI":"10.1371\/journal.ppat.1003578","article-title":"Aggressive Chemotherapy and the Selection of Drug Resistant Pathogens","volume":"9","author":"S Huijben","year":"2013","journal-title":"PLoS Pathog"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"8348","DOI":"10.1073\/pnas.0832373100","article-title":"A Bayesian framework for combining heterogeneous data sources for gene function prediction (in Saccharomyces cerevisiae)","volume":"100","author":"OG Troyanskaya","year":"2003","journal-title":"Proc Natl Acad Sci"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrg1318","article-title":"The Bayesian revolution in genetics","volume":"5","author":"MA Beaumont","year":"2004","journal-title":"Nat Rev Genet"},{"key":"ref38","author":"D Husmeir","year":"2005"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1126\/science.1105809","article-title":"Causal Protein-Signaling Networks Derived from Multiparameter Single-Cell Data","volume":"308","author":"K Sachs","year":"2005","journal-title":"Science"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1038\/nbt0904-1177","article-title":"What is Bayesian statistics?","volume":"22","author":"SR Eddy","year":"2004","journal-title":"Nat Biotechnol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nrg2778","article-title":"The population genetics of antibiotic resistance: integrating molecular mechanisms and treatment contexts","volume":"11","author":"RC MacLean","year":"2010","journal-title":"Nat Rev Genet"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"e0122283","DOI":"10.1371\/journal.pone.0122283","article-title":"Rational Design of Antibiotic Treatment Plans: A Treatment Strategy for Managing Evolution and Reversing Resistance","volume":"10","author":"PM Mira","year":"2015","journal-title":"PLOS ONE"},{"key":"ref43","unstructured":"Stearns, Sthepen C. M Ruslan. Evolutionary Medicine. First. Sinauer Associates; 2015."},{"key":"ref44","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1172\/JCI200316814","article-title":"Application of a mathematical model to prevent in vivo amplification of antibiotic-resistant bacterial populations during therapy","volume":"112","author":"N Jumbe","year":"2003","journal-title":"J Clin Invest"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1126\/science.135.3508.1067","article-title":"Synergism between Streptomycin and Penicillin: A Proposed Mechanism","volume":"135","author":"PH Plotz","year":"1962","journal-title":"Science"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"262ra156","DOI":"10.1126\/scitranslmed.3009940","article-title":"Prediction of resistance development against drug combinations by collateral responses to component drugs","volume":"6","author":"C Munck","year":"2014","journal-title":"Sci Transl Med"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1093\/molbev\/msv006","article-title":"Collateral Resistance and Sensitivity Modulate Evolution of High-Level Resistance to Drug Combination Treatment in Staphylococcus aureus","volume":"32","author":"MR de Evgrafov","year":"2015","journal-title":"Mol Biol Evol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/0002-9343(86)90490-0","article-title":"Aminoglycosides plus beta-lactams against gram-negative organisms: Evaluation of in vitro synergy and chemical interactions","volume":"80","author":"H Giamarellou","year":"1986","journal-title":"Am J Med"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1093\/cid\/ciu069","article-title":"Treatment of Multidrug-Resistant Gram-Negative Infections in Children","volume":"58","author":"AJ Hsu","year":"2014","journal-title":"Clin Infect Dis"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"12254","DOI":"10.1073\/pnas.1201281109","article-title":"Mechanism-independent method for predicting response to multidrug combinations in bacteria","volume":"109","author":"K Wood","year":"2012","journal-title":"Proc Natl Acad Sci"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"10442","DOI":"10.1073\/pnas.1606301113","article-title":"Prediction of multidimensional drug dose responses based on measurements of drug pairs","volume":"113","author":"A Zimmer","year":"2016","journal-title":"Proc Natl Acad Sci"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"e00747","DOI":"10.7554\/eLife.00747","article-title":"Evolutionary dynamics of cancer in response to targeted combination therapy","volume":"2","author":"I Bozic","year":"2013","journal-title":"eLife"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1056\/NEJMoa1508887","article-title":"Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F","volume":"374","author":"AT Shaw","year":"2015","journal-title":"N Engl J Med"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.drup.2012.03.002","article-title":"Collateral sensitivity as a strategy against cancer multidrug resistance","volume":"15","author":"KM Pluchino","year":"2012","journal-title":"Drug Resist Updat"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1038\/s41598-017-00791-8","article-title":"Collateral sensitivity networks reveal evolutionary instability and novel treatment strategies in ALK mutated non-small cell lung cancer","volume":"7","author":"A Dhawan","year":"2017","journal-title":"Sci Rep"},{"key":"ref56"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"e0146021","DOI":"10.1371\/journal.pone.0146021","article-title":"Dose-Response Analysis Using R","volume":"10","author":"C Ritz","year":"2015","journal-title":"PLOS ONE"},{"key":"ref58","first-page":"255","article-title":"Proceedings of the Sixth Annual Conference on Uncertainty in Artificial Intelligence","author":"T Verma","year":"1991"},{"key":"ref59","first-page":"4","author":"S Yaramakala","year":"2005"},{"key":"ref60","article-title":"Learning Bayesian Networks with the bnlearn R Package","author":"M Scutari","year":"2010","journal-title":"J Stat Softw"}],"updated-by":[{"DOI":"10.1371\/journal.pbio.2004356","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T00:00:00Z","timestamp":1525910400000}}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pbio.2004356","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T11:32:19Z","timestamp":1604230339000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.2004356"}},"subtitle":[],"editor":[{"given":"Andrew","family":"Read","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,4,30]]},"references-count":60,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,4,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.2004356","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pbio.2004356","asserted-by":"object"}]},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,30]]}}}