{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:44:58Z","timestamp":1791830698613,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1014827","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000}}],"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["NSF 2406985"],"award-info":[{"award-number":["NSF 2406985"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["BROWN23I0"],"award-info":[{"award-number":["BROWN23I0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014037","name":"National Defense Science and Engineering Graduate","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014037","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008227","name":"Achievement Rewards for College Scientists Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008227","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100029746","name":"National Research Council Research Associateship Programs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100029746","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Antibiotics are a cornerstone of modern medicine, targeting pathogen cells by disrupting essential cellular processes. However, standard antibiotic susceptibility metrics (e.g., MIC) and textbook models neglect transient dynamics and density-dependent effects, despite their ubiquity in nature. In clinical infections, where bacterial populations are the units we treat, this can increase the risk of under treatment. To address this gap, we generate high resolution optical density time series data for\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    (3 antibiotics, 12 doses, 7 inoculum sizes, 4x replication), enabling gradient estimation and gradient-based model parameterization. We develop a dynamics-led computational pipeline that (1) evaluates population scale ordinary differential equation models in the context of estimated time derivative data, and (2) classifies transient dynamics in dose-inoculum space using unsupervised clustering. Applied to our data, the pipeline identifies an ordinary differential equation model with a saturating antibiotic-loss term and a threshold-dependent weak Allee term that recapitulates and quantifies classic rate, yield, and inoculum effects of antibiotics. In addition, our model and clustering approach suggest a set of novel metrics, defining thresholds separating distinct dynamical regimes. Beyond antibiotic data sets, our approach utilizing a derivative-based fitting algorithm and clustering of derivative trajectories is applicable to any biological time series with controlled perturbations and variable initial conditions.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1014827","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:54:57Z","timestamp":1791222897000},"page":"e1014827","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantifying antibiotic susceptibility and inoculum effects using transient dynamics of Pseudomonas aeruginosa"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5064-0294","authenticated-orcid":true,"given":"Sarah","family":"Sundius","sequence":"first","affiliation":[{"name":"Interdisciplinary Program in Quantitative Biosciences, Georgia Institute of Technology","place":["Atlanta, Georgia, United States of America"]},{"name":"School of Mathematics, Georgia Institute of Technology","place":["Atlanta, Georgia, United States of America"]},{"name":"Center for Microbial Dynamics and Infection, Georgia Institute of Technology","place":["Atlanta, Georgia, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Farrell","sequence":"additional","affiliation":[{"name":"Center for Microbial Dynamics and Infection, Georgia Institute of Technology","place":["Atlanta, Georgia, United States of America"]},{"name":"School of Biological Sciences, Georgia Institute of Technology","place":["Atlanta, Georgia, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly L.","family":"Eick","sequence":"additional","affiliation":[{"name":"Center for Microbial Dynamics and Infection, Georgia Institute of Technology","place":["Atlanta, Georgia, United States of America"]},{"name":"School of Biological Sciences, Georgia Institute of Technology","place":["Atlanta, Georgia, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Kuske","sequence":"additional","affiliation":[{"name":"School of Mathematics, Georgia Institute of Technology","place":["Atlanta, Georgia, United States of America"]},{"name":"Center for Microbial Dynamics and Infection, Georgia Institute of Technology","place":["Atlanta, Georgia, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam P.","family":"Brown","sequence":"additional","affiliation":[{"name":"Center for Microbial Dynamics and Infection, Georgia Institute of Technology","place":["Atlanta, Georgia, United States of America"]},{"name":"School of Biological Sciences, Georgia Institute of Technology","place":["Atlanta, Georgia, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"issue":"3","key":"pcbi.1014827.ref001","doi-asserted-by":"crossref","first-page":"300","DOI":"10.4103\/joacp.JOACP_349_15","article-title":"Action and resistance mechanisms of antibiotics: A guide for clinicians","volume":"33","author":"G Kapoor","year":"2017","journal-title":"J Anaesthesiol Clin Pharmacol"},{"key":"pcbi.1014827.ref002","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.32976","article-title":"Antibiotic-induced population fluctuations and stochastic clearance of bacteria","volume":"7","author":"J Coates","year":"2018","journal-title":"eLife"},{"issue":"5","key":"pcbi.1014827.ref003","doi-asserted-by":"crossref","DOI":"10.1093\/femsle\/fnaa012","article-title":"Mathematical modeling of the \u201cinoculum effect\u201d: six applicable models and the MIC advancement point concept","volume":"367","author":"JR Salas","year":"2020","journal-title":"FEMS Microbiol Lett"},{"issue":"4","key":"pcbi.1014827.ref004","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1093\/jac\/dkn554","article-title":"Functional relationship between bacterial cell density and the efficacy of antibiotics","volume":"63","author":"KI Udekwu","year":"2009","journal-title":"J Antimicrob Chemother"},{"issue":"3","key":"pcbi.1014827.ref005","doi-asserted-by":"crossref","DOI":"10.1128\/spectrum.04091-22","article-title":"What\u2019s the Matter with MICs: Bacterial Nutrition, Limiting Resources, and Antibiotic Pharmacodynamics","volume":"11","author":"BA Berryhill","year":"2023","journal-title":"Microbiol Spectr"},{"issue":"10","key":"pcbi.1014827.ref006","doi-asserted-by":"crossref","first-page":"2825","DOI":"10.1093\/jac\/dkz226","article-title":"Inoculum effect of \u03b2-lactam antibiotics","volume":"74","author":"JR Lenhard","year":"2019","journal-title":"J Antimicrob Chemother"},{"issue":"3","key":"pcbi.1014827.ref007","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1093\/clinids\/11.3.361","article-title":"Inoculum Effect","volume":"11","author":"I Brook","year":"1989","journal-title":"Clin Infect Dis"},{"issue":"10","key":"pcbi.1014827.ref008","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1005098","article-title":"Population Density Modulates Drug Inhibition and Gives Rise to Potential Bistability of Treatment Outcomes for Bacterial Infections","volume":"12","author":"J Karslake","year":"2016","journal-title":"PLoS Comput Biol"},{"key":"pcbi.1014827.ref009","first-page":"617","article-title":"The inoculum effect and band-pass bacterial response to periodic antibiotic treatment","volume":"8","author":"C Tan","year":"2012","journal-title":"Mol Syst Biol"},{"issue":"1","key":"pcbi.1014827.ref010","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3390\/antibiotics10010087","article-title":"Bistable Bacterial Growth Dynamics in the Presence of Antimicrobial Agents","volume":"10","author":"N Frenkel","year":"2021","journal-title":"Antibiotics (Basel)"},{"issue":"3","key":"pcbi.1014827.ref011","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/nchembio.1754","article-title":"Collective antibiotic tolerance: mechanisms, dynamics and intervention","volume":"11","author":"HR Meredith","year":"2015","journal-title":"Nat Chem Biol"},{"issue":"2","key":"pcbi.1014827.ref012","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1007\/s00285-005-0350-6","article-title":"A new modeling approach to the effect of antimicrobial agents on heterogeneous microbial populations","volume":"52","author":"M Nikolaou","year":"2006","journal-title":"J Math Biol"},{"issue":"50","key":"pcbi.1014827.ref013","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.add0924","article-title":"Growth productivity as a determinant of the inoculum effect for bactericidal antibiotics","volume":"8","author":"G Diaz-Tang","year":"2022","journal-title":"Sci Adv"},{"issue":"6","key":"pcbi.1014827.ref014","doi-asserted-by":"crossref","DOI":"10.1016\/j.molcel.2017.11.012","article-title":"Understanding and Sensitizing Density-Dependent Persistence to Quinolone Antibiotics","volume":"68","author":"A Gutierrez","year":"2017","journal-title":"Mol Cell"},{"key":"pcbi.1014827.ref015","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/msb.2013.39","article-title":"Bacterial cheating drives the population dynamics of cooperative antibiotic resistance plasmids","volume":"9","author":"EA Yurtsev","year":"2013","journal-title":"Mol Syst Biol"},{"key":"pcbi.1014827.ref016","doi-asserted-by":"crossref","DOI":"10.1101\/550368","article-title":"The pharmacodynamic inoculum effect from the perspective of bacterial population modeling","author":"DY Baeder","year":"2019","journal-title":"Pharmacol Toxicol"},{"key":"pcbi.1014827.ref017","doi-asserted-by":"crossref","DOI":"10.1101\/2020.08.21.260620","article-title":"Inoculum effect of antimicrobial peptides","author":"MR Loffredo","year":"2020","journal-title":"Biophysics"},{"issue":"287","key":"pcbi.1014827.ref018","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaa8760","article-title":"Classic reaction kinetics can explain complex patterns of antibiotic action","volume":"7","author":"P Abel Zur Wiesch","year":"2015","journal-title":"Sci Transl Med"},{"issue":"8","key":"pcbi.1014827.ref019","doi-asserted-by":"crossref","first-page":"088101","DOI":"10.1103\/PhysRevLett.109.088101","article-title":"Mutational pathway determines whether drug gradients accelerate evolution of drug-resistant cells","volume":"109","author":"P Greulich","year":"2012","journal-title":"Phys Rev Lett"},{"issue":"3","key":"pcbi.1014827.ref020","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1128\/AAC.8.3.344","article-title":"Effect of inoculum and of beta-lactamase on the anti-staphylococcal activity of thirteen penicillins and cephalosporins","volume":"8","author":"LD Sabath","year":"1975","journal-title":"Antimicrob Agents Chemother"},{"issue":"5418","key":"pcbi.1014827.ref021","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.284.5418.1318","article-title":"Bacterial biofilms: a common cause of persistent infections","volume":"284","author":"JW Costerton","year":"1999","journal-title":"Science"},{"issue":"2","key":"pcbi.1014827.ref022","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/nprot.2007.521","article-title":"Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances","volume":"3","author":"I Wiegand","year":"2008","journal-title":"Nat Protoc"},{"key":"pcbi.1014827.ref023","unstructured":"Wikler M. Guideline M7-A7: Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; Approved Standard. 2006."},{"issue":"2","key":"pcbi.1014827.ref024","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3390\/pathogens10020165","article-title":"The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance","volume":"10","author":"B Kowalska-Krochmal","year":"2021","journal-title":"Pathogens"},{"key":"pcbi.1014827.ref025","volume-title":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. CLSI standard M07","author":"Clinical and Laboratory Standards Institute","year":"2018"},{"issue":"6","key":"pcbi.1014827.ref026","doi-asserted-by":"crossref","first-page":"803","DOI":"10.2165\/00003495-200868060-00006","article-title":"Meropenem: a review of its use in the treatment of serious bacterial infections","volume":"68","author":"CM Baldwin","year":"2008","journal-title":"Drugs"},{"issue":"8","key":"pcbi.1014827.ref027","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a025247","article-title":"Eqn90-lactams and Eqn91-lactamase inhibitors: an overview","volume":"6","author":"K Bush","year":"2016","journal-title":"Cold Spring Harbor Perspect Med"},{"issue":"10","key":"pcbi.1014827.ref028","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0169-5347(99)01683-3","article-title":"Inverse density dependence and the Allee effect","volume":"14","author":"F Courchamp","year":"1999","journal-title":"Trends Ecol Evol"},{"issue":"2241","key":"pcbi.1014827.ref029","first-page":"20200350","article-title":"Unpacking the Allee effect: determining individual-level mechanisms that drive global population dynamics","volume":"476","author":"NT Fadai","year":"2020","journal-title":"Proc Math Phys Eng Sci"},{"issue":"8","key":"pcbi.1014827.ref030","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00433-18","article-title":"The Inoculum Effect in the Era of Multidrug Resistance: Minor Differences in Inoculum Have Dramatic Effect on MIC Determination","volume":"62","author":"KP Smith","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"pcbi.1014827.ref031","unstructured":"Clinical and Laboratory Standards Institute. Performance Standards for Anti-Microbial Susceptibility Testing. CLSI standard M100. 2020."},{"issue":"11","key":"pcbi.1014827.ref032","doi-asserted-by":"crossref","first-page":"4739","DOI":"10.1128\/AAC.01831-09","article-title":"Mathematical modeling to characterize the inoculum effect","volume":"54","author":"P Bhagunde","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"issue":"10","key":"pcbi.1014827.ref033","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.1128\/AAC.48.10.3670-3676.2004","article-title":"Pharmacodynamic functions: a multiparameter approach to the design of antibiotic treatment regimens","volume":"48","author":"RR Regoes","year":"2004","journal-title":"Antimicrob Agents Chemother"},{"issue":"8","key":"pcbi.1014827.ref034","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1128\/AAC.00381-10","article-title":"Population dynamics of antibiotic treatment: a mathematical model and hypotheses for time-kill and continuous-culture experiments","volume":"54","author":"BR Levin","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"pcbi.1014827.ref035","article-title":"Pharmacodynamics, population dynamics, and the evolution of persistence in Staphylococcus aureus","volume":"9","author":"PJT Johnson","year":"2013","journal-title":"PLoS Genet"},{"issue":"12","key":"pcbi.1014827.ref036","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1003388","article-title":"Ecological modeling from time-series inference: insight into dynamics and stability of intestinal microbiota","volume":"9","author":"RR Stein","year":"2013","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"pcbi.1014827.ref037","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s13059-016-0980-6","article-title":"MDSINE: Microbial Dynamical Systems INference Engine for microbiome time-series analyses","volume":"17","author":"V Bucci","year":"2016","journal-title":"Genome Biol"},{"key":"pcbi.1014827.ref038","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s12859-016-1016-7","article-title":"Growthcurver: an R package for obtaining interpretable metrics from microbial growth curves","volume":"17","author":"K Sprouffske","year":"2016","journal-title":"BMC Bioinform"},{"issue":"1","key":"pcbi.1014827.ref039","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1093\/molbev\/mst187","article-title":"Growth Rates Made Easy","volume":"31","author":"BG Hall","year":"2014","journal-title":"Mol Biol Evol"},{"issue":"3","key":"pcbi.1014827.ref040","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1007\/s12155-015-9584-3","article-title":"Modeling Microbial Growth Curves with GCAT","volume":"8","author":"YV Bukhman","year":"2015","journal-title":"Bioenerg Res"},{"issue":"17","key":"pcbi.1014827.ref041","doi-asserted-by":"crossref","first-page":"6103","DOI":"10.1128\/AEM.01245-12","article-title":"Alternative approach to modeling bacterial lag time, using logistic regression as a function of time, temperature, pH, and sodium chloride concentration","volume":"78","author":"S Koseki","year":"2012","journal-title":"Appl Environ Microbiol"},{"issue":"7","key":"pcbi.1014827.ref042","doi-asserted-by":"crossref","DOI":"10.18637\/jss.v033.i07","article-title":"grofit: Fitting Biological Growth Curves withR","volume":"33","author":"M Kahm","year":"2010","journal-title":"J Stat Soft"},{"key":"pcbi.1014827.ref043","unstructured":"MacQueen J. Some methods for classification and analysis of multivariate observations. 1967. Available from: https:\/\/api.semanticscholar.org\/CorpusID:6278891"},{"issue":"3","key":"pcbi.1014827.ref044","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1006\/jtbi.2002.3084","article-title":"Single-species models of the Allee effect: extinction boundaries, sex ratios and mate encounters","volume":"218","author":"DS Boukal","year":"2002","journal-title":"J Theor Biol"},{"issue":"1","key":"pcbi.1014827.ref045","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1006\/tpbi.1997.1340","article-title":"Interactions between local dynamics and dispersal: insights from single species models","volume":"53","author":"P Amarasekare","year":"1998","journal-title":"Theor Popul Biol"},{"issue":"1533","key":"pcbi.1014827.ref046","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1098\/rstb.2009.0055","article-title":"Social evolution in micro-organisms and a Trojan horse approach to medical intervention strategies","volume":"364","author":"SP Brown","year":"2009","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"7","key":"pcbi.1014827.ref047","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.foodres.2007.01.012","article-title":"The logistic (Verhulst) model for sigmoid microbial growth curves revisited","volume":"40","author":"M Peleg","year":"2007","journal-title":"Food Res Int"},{"key":"pcbi.1014827.ref048","unstructured":"Omer TA. Analysis of bacterial population growth using extended logistic growth model with distributed delay. 2018. https:\/\/doi.org\/10.48550\/ARXIV.1807.09108"},{"issue":"6","key":"pcbi.1014827.ref049","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s11538-020-00756-5","article-title":"Population Dynamics with Threshold Effects Give Rise to a Diverse Family of Allee Effects","volume":"82","author":"NT Fadai","year":"2020","journal-title":"Bull Math Biol"},{"issue":"1","key":"pcbi.1014827.ref050","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s42003-020-01127-5","article-title":"Robust estimation of bacterial cell count from optical density","volume":"3","author":"J Beal","year":"2020","journal-title":"Commun Biol"},{"issue":"10","key":"pcbi.1014827.ref051","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0276040","article-title":"Estimating microbial population data from optical density","volume":"17","author":"P Mira","year":"2022","journal-title":"PLoS One"},{"key":"pcbi.1014827.ref052","doi-asserted-by":"crossref","first-page":"38828","DOI":"10.1038\/srep38828","article-title":"General calibration of microbial growth in microplate readers","volume":"6","author":"K Stevenson","year":"2016","journal-title":"Sci Rep"},{"issue":"51","key":"pcbi.1014827.ref053","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1810840115","article-title":"Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora","volume":"115","author":"C Tedijanto","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"pcbi.1014827.ref054","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3000250","article-title":"Resistance diagnostics as a public health tool to combat antibiotic resistance: A model-based evaluation","volume":"17","author":"D McAdams","year":"2019","journal-title":"PLoS Biol"},{"issue":"1","key":"pcbi.1014827.ref055","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.01349-22","article-title":"Defining the Benefits of Antibiotic Resistance in Commensals and the Scope for Resistance Optimization","volume":"14","author":"K Wollein Waldetoft","year":"2023","journal-title":"mBio"},{"issue":"5","key":"pcbi.1014827.ref056","doi-asserted-by":"crossref","DOI":"10.1128\/msphere.00318-22","article-title":"Antibiotics Drive Expansion of Rare Pathogens in a Chronic Infection Microbiome Model","volume":"7","author":"JJ Varga","year":"2022","journal-title":"mSphere"},{"issue":"6458","key":"pcbi.1014827.ref057","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1126\/science.aax3879","article-title":"The evolution of antibiotic resistance","volume":"365","author":"RC MacLean","year":"2019","journal-title":"Science"},{"issue":"2","key":"pcbi.1014827.ref058","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1093\/jac\/dkm481","article-title":"Clinical impact of reducing routine susceptibility testing in chronic Pseudomonas aeruginosa infections in cystic fibrosis","volume":"61","author":"C Etherington","year":"2008","journal-title":"J Antimicrob Chemother"},{"issue":"5","key":"pcbi.1014827.ref059","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1586\/14787210.4.5.711","article-title":"Is there value in susceptibility testing of Pseudomonas aeruginosa causing chronic infection in patients with cystic fibrosis?","volume":"4","author":"PH Gilligan","year":"2006","journal-title":"Exp Rev Anti-Infect Therapy"},{"issue":"5","key":"pcbi.1014827.ref060","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1378\/chest.123.5.1495","article-title":"Susceptibility testing of Pseudomonas aeruginosa isolates and clinical response to parenteral antibiotic administration: lack of association in cystic fibrosis","volume":"123","author":"AL Smith","year":"2003","journal-title":"Chest"},{"issue":"5","key":"pcbi.1014827.ref061","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.tim.2012.02.004","article-title":"Stress responses as determinants of antimicrobial resistance in Gram-negative bacteria","volume":"20","author":"K Poole","year":"2012","journal-title":"Trends Microbiol"},{"issue":"4","key":"pcbi.1014827.ref062","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nrmicro2977","article-title":"Competition sensing: the social side of bacterial stress responses","volume":"11","author":"DM Cornforth","year":"2013","journal-title":"Nat Rev Microbiol"},{"issue":"6268","key":"pcbi.1014827.ref063","doi-asserted-by":"crossref","DOI":"10.1126\/science.aad3292","article-title":"Multidrug evolutionary strategies to reverse antibiotic resistance","volume":"351","author":"M Baym","year":"2016","journal-title":"Science"},{"issue":"2","key":"pcbi.1014827.ref064","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1073\/pnas.1811887116","article-title":"Structured environments fundamentally alter dynamics and stability of ecological communities","volume":"116","author":"N Vallespir Lowery","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"pcbi.1014827.ref065","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1111\/ele.13241","article-title":"The rate of environmental fluctuations shapes ecological dynamics in a two-species microbial system","volume":"22","author":"A Rodr\u00edguez-Verdugo","year":"2019","journal-title":"Ecol Lett"},{"issue":"1","key":"pcbi.1014827.ref066","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/s42003-023-05281-4","article-title":"The non-attached biofilm aggregate","volume":"6","author":"KN Kragh","year":"2023","journal-title":"Commun Biol"},{"issue":"9","key":"pcbi.1014827.ref067","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.tim.2013.06.002","article-title":"The in vivo biofilm","volume":"21","author":"T Bjarnsholt","year":"2013","journal-title":"Trends Microbiol"},{"issue":"15","key":"pcbi.1014827.ref068","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1073\/pnas.1517384113","article-title":"Discovering governing equations from data by sparse identification of nonlinear dynamical systems","volume":"113","author":"SL Brunton","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pcbi.1014827.ref069","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1128\/AAC.01901-13","article-title":"Rapid conversion of Pseudomonas aeruginosa to a spherical cell morphotype facilitates tolerance to carbapenems and penicillins but increases susceptibility to antimicrobial peptides","volume":"58","author":"LG Monahan","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"issue":"11","key":"pcbi.1014827.ref070","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1007\/s100960050180","article-title":"Antibacterial activity of meropenem against Pseudomonas aeruginosa, including antibiotic-induced morphological changes and endotoxin-liberating effects","volume":"17","author":"M Trautmann","year":"1998","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"11","key":"pcbi.1014827.ref071","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1111\/j.1469-0691.2010.03189.x","article-title":"The exclusion of dead bacterial cells is essential for accurate molecular analysis of clinical samples","volume":"16","author":"GB Rogers","year":"2010","journal-title":"Clin Microbiol Infect"},{"key":"pcbi.1014827.ref072","doi-asserted-by":"crossref","DOI":"10.3389\/fsysb.2022.1021897","article-title":"Methods of quantifying interactions among populations using Lotka-Volterra models","volume":"2","author":"JD Davis","year":"2022","journal-title":"Front Syst Biol"},{"key":"pcbi.1014827.ref073","unstructured":"The MathWorks Inc. kmeans Documentation. 2026. Available from: https:\/\/www.mathworks.com\/help\/stats\/kmeans.html"},{"key":"pcbi.1014827.ref074","unstructured":"The MathWorks Inc. MATLAB version: 9.11.0 (R2021b). 2021. Available from: https:\/\/www.mathworks.com"},{"key":"pcbi.1014827.ref075","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0377-0427(87)90125-7","article-title":"Silhouettes: A graphical aid to the interpretation and validation of cluster analysis","volume":"20","author":"PJ Rousseeuw","year":"1987","journal-title":"J Comput Appl Math"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1014827","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1014827","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:47:50Z","timestamp":1791827270000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1014827"}},"subtitle":[],"editor":[{"given":"Tyler","family":"Cassidy","sequence":"first","affiliation":[{"name":"The University of British Columbia","place":["CANADA"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":75,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1014827","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]}}}