{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T20:28:40Z","timestamp":1782160120029,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013425","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000}}],"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Temple University\u2019s Office of the Vice President for Research"},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["HL155694"],"award-info":[{"award-number":["HL155694"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>A biofilm is a community of microorganisms adhered to a surface, bound together by extracellular polymeric substances (EPS). They are ubiquitous in nature and develop on a range of surfaces including living tissue. Biofilms themselves typically do not negatively affect their host, but under certain conditions they can retain pathogenic features and cause a wide range of illnesses including persistent or chronic infections. In this study, we look at the bacterium <jats:italic>Enterococcus faecalis<\/jats:italic>. <jats:italic>E. faecalis<\/jats:italic> is a gram-positive, commensal bacterium commonly found in the human gastrointestinal tract. Generally, commensal <jats:italic>E. faecalis<\/jats:italic> does not negatively impact human health, but pathogenic strains have been found to acquire mobile genetic elements, including plasmids. When <jats:italic>E. faecalis<\/jats:italic> with the pCF10 plasmid forms a biofilm it constructs raised complex structures with variable cellular packing, including aggregates, instead of a homogeneous and less densely packed biofilm above a rigid base. This reconfiguration of the biofilm confers resistance to high levels of erythromycin. For this study, we carried out biological experiments which show that pCF10-containing <jats:italic>E. faecalis<\/jats:italic> biofilms undergo a rapid reconfiguration of its initial architecture, resulting in a doubling of cellular population over a single hour of antibiotic treatment. We developed a mathematical and computational model, calibrated using image processing techniques, to identify the characteristics of the biofilm\u2019s spatial architecture that allow for the rapid one-hour reconfiguration under treatment. This model involves both stochastic cellular automata and deterministic partial differential equations. The numerical simulations carried out in this study demonstrate that biofilm survival requires both the robust formation of initial complex structures and an associated extracellular DNA (eDNA) cloud. These findings highlight the fundamental role of biofilm heterogeneity, containing aggregated structures with an associated eDNA cloud, in erythromycin resistance of <jats:italic>E. faecalis<\/jats:italic> with the pCF10 plasmid. The identification of eDNA as a target to increase the susceptibility of the biofilm to erythromycin could ultimately improve antibiotic treatment protocols.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1013425","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T20:03:35Z","timestamp":1756843415000},"page":"e1013425","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Using stochastic cellular automata to model and define sufficient conditions for the survival of Enterococcus faecalis biofilms with the pCF10 plasmid under erythromycin 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Schulze","year":"2021","journal-title":"Microb Cell."},{"issue":"3","key":"pcbi.1013425.ref005","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.MB-0010-2014","article-title":"Antimicrobial tolerance in biofilms","volume":"3","author":"PS Stewart","year":"2015","journal-title":"Microbiol Spectr."},{"issue":"3","key":"pcbi.1013425.ref006","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1046\/j.1365-2672.2001.01413.x","article-title":"Biofilm penetration and disinfection efficacy of alkaline hypochlorite and chlorosulfamates","volume":"91","author":"PS Stewart","year":"2001","journal-title":"J Appl Microbiol."},{"issue":"11","key":"pcbi.1013425.ref007","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1128\/AAC.40.11.2517","article-title":"Theoretical aspects of antibiotic diffusion into microbial biofilms","volume":"40","author":"PS Stewart","year":"1996","journal-title":"Antimicrob Agents 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Microbiol."},{"issue":"1","key":"pcbi.1013425.ref011","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S0966-842X(00)01913-2","article-title":"Mechanisms of biofilm resistance to antimicrobial agents","volume":"9","author":"TF Mah","year":"2001","journal-title":"Trends Microbiol."},{"issue":"4","key":"pcbi.1013425.ref012","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1128\/AAC.45.4.999-1007.2001","article-title":"Riddle of biofilm resistance","volume":"45","author":"K Lewis","year":"2001","journal-title":"Antimicrob Agents Chemother."},{"issue":"9","key":"pcbi.1013425.ref013","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1080\/08927014.2011.626899","article-title":"Resistance of bacterial biofilms to disinfectants: a review","volume":"27","author":"A Bridier","year":"2011","journal-title":"Biofouling."},{"issue":"1","key":"pcbi.1013425.ref014","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.tim.2004.11.010","article-title":"Survival strategies of infectious biofilms","volume":"13","author":"CA Fux","year":"2005","journal-title":"Trends Microbiol."},{"issue":"4","key":"pcbi.1013425.ref015","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s11908-000-0009-9","article-title":"Pathogenic mechanisms of enterococcal endocarditis","volume":"2","author":"J McCormick","year":"2000","journal-title":"Curr Infect Dis Rep."},{"issue":"3","key":"pcbi.1013425.ref016","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1128\/AAC.41.3.702","article-title":"High-level plasmid-mediated gentamicin resistance and pheromone response of plasmids present in clinical isolates of Enterococcus faecalis","volume":"41","author":"M Shiojima","year":"1997","journal-title":"Antimicrob Agents 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Genet."},{"issue":"15","key":"pcbi.1013425.ref020","doi-asserted-by":"crossref","first-page":"4537","DOI":"10.1128\/AEM.00363-16","article-title":"Antagonistic donor density effect conserved in multiple enterococcal conjugative plasmids","volume":"82","author":"A Bandyopadhyay","year":"2016","journal-title":"Appl Environ Microbiol."},{"issue":"17","key":"pcbi.1013425.ref021","doi-asserted-by":"crossref","first-page":"7086","DOI":"10.1073\/pnas.1212256110","article-title":"Antagonistic self-sensing and mate-sensing signaling controls antibiotic-resistance transfer","volume":"110","author":"A Chatterjee","year":"2013","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"8","key":"pcbi.1013425.ref022","article-title":"Bistability versus bimodal distributions in gene regulatory processes from population balance","volume":"7","author":"C-C Shu","year":"2011","journal-title":"PLoS Comput 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Microbiol."},{"key":"pcbi.1013425.ref026","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41522-017-0023-4","article-title":"Restructuring of Enterococcus faecalis biofilm architecture in response to antibiotic-induced stress","volume":"3","author":"JL Dale","year":"2017","journal-title":"NPJ Biofilms Microbiomes."},{"issue":"6","key":"pcbi.1013425.ref027","doi-asserted-by":"crossref","first-page":"135","DOI":"10.2166\/wst.2001.0358","article-title":"Effect of EPS on biofilm structure and function as revealed by an individual-based model of biofilm growth","volume":"43","author":"J-U Kreft","year":"2001","journal-title":"Water Sci Technol."},{"issue":"12","key":"pcbi.1013425.ref028","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1038\/s41559-023-02230-6","article-title":"Community composition and the environment modulate the population dynamics of type VI secretion in human gut bacteria","volume":"7","author":"S Robitaille","year":"2023","journal-title":"Nat Ecol Evol."},{"key":"pcbi.1013425.ref029","doi-asserted-by":"crossref","first-page":"016706","DOI":"10.1103\/PhysRevE.72.016706","article-title":"Domain-decomposition method for parallel lattice Boltzmann simulation of incompressible flow in porous media","volume":"72","author":"J Wang","year":"2005","journal-title":"Phys Rev E Stat Nonlin Soft Matter Phys."},{"issue":"1","key":"pcbi.1013425.ref030","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/(SICI)1097-0290(19980405)58:1<101::AID-BIT11>3.0.CO;2-M","article-title":"Mathematical modeling of biofilm structure with a hybrid differential-discrete cellular automaton approach","volume":"58","author":"C Picioreanu","year":"1998","journal-title":"Biotechnol Bioeng."},{"key":"pcbi.1013425.ref031","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s12038-020-00092-9","article-title":"Quorum sensing-induced phenotypic switching as a regulatory nutritional stress response in a competitive two-species biofilm: An individual-based cellular automata model","volume":"45","author":"TR Chirathanamettu","year":"2020","journal-title":"J Biosci."},{"issue":"7","key":"pcbi.1013425.ref032","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1007\/s11538-014-9974-2","article-title":"Individual-based model for quorum sensing with background flow","volume":"76","author":"H Uecker","year":"2014","journal-title":"Bull Math Biol."},{"issue":"3","key":"pcbi.1013425.ref033","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1007\/s11538-017-0246-9","article-title":"Influence of Nutrient availability and quorum sensing on the formation of metabolically inactive microcolonies within structurally heterogeneous bacterial biofilms: an individual-based 3D cellular automata model","volume":"79","author":"L Machineni","year":"2017","journal-title":"Bull Math Biol."},{"issue":"3","key":"pcbi.1013425.ref034","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1137\/S0036139900371709","article-title":"Finger formation in biofilm layers","volume":"62","author":"I Klapper","year":"2002","journal-title":"SIAM J Appl Math."},{"issue":"3","key":"pcbi.1013425.ref035","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1080\/10273660108833072","article-title":"A new deterministic spatio-temporal continuum model for biofilm development","volume":"3","author":"HJ Eberl","year":"2000","journal-title":"Comput Math Methods Med."},{"issue":"4","key":"pcbi.1013425.ref036","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.bulm.2003.11.008","article-title":"Effect of heterogeneous structure in mechanically unstressed biofilms on overall growth","volume":"66","author":"I Klapper","year":"2004","journal-title":"Bull Math Biol."},{"issue":"3","key":"pcbi.1013425.ref037","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/bit.10376","article-title":"Viscoelastic fluid description of bacterial biofilm material properties","volume":"80","author":"I Klapper","year":"2002","journal-title":"Biotechnol Bioeng."},{"key":"pcbi.1013425.ref038","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1742-4682-8-8","article-title":"A mathematical model of quorum sensing regulated EPS production in biofilm communities","volume":"8","author":"MR Frederick","year":"2011","journal-title":"Theor Biol Med Model."},{"issue":"3","key":"pcbi.1013425.ref039","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/bit.260280304","article-title":"A multispecies biofilm model","volume":"28","author":"O Wanner","year":"1986","journal-title":"Biotechnol Bioeng."},{"issue":"1","key":"pcbi.1013425.ref040","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1006\/bulm.2000.0205","article-title":"A mathematical model for quorum sensing in Pseudomonas aeruginosa","volume":"63","author":"JD Dockery","year":"2001","journal-title":"Bull Math Biol."},{"key":"pcbi.1013425.ref041","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jtbi.2015.11.010","article-title":"A 3D numerical study of antimicrobial persistence in heterogeneous multi-species biofilms","volume":"392","author":"J Zhao","year":"2016","journal-title":"J Theor Biol."},{"issue":"3","key":"pcbi.1013425.ref042","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0009-2509(97)00319-9","article-title":"Diffusion and reaction in biofilms","volume":"53","author":"BD Wood","year":"1998","journal-title":"Chem Eng Sci."},{"key":"pcbi.1013425.ref043","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1016\/j.advwatres.2006.05.030","article-title":"Hierarchical simulator of biofilm growth and dynamics in granular porous materials","volume":"30","author":"GE Kapellos","year":"2007","journal-title":"Adv Water Resourc."},{"issue":"6","key":"pcbi.1013425.ref044","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1017\/S0956792518000554","article-title":"Time adaptive numerical solution of a highly non-linear degenerate cross-diffusion system arising in multi-species biofilm modelling","volume":"29","author":"M Ghasemi","year":"2018","journal-title":"Eur J Appl Math."},{"issue":"10","key":"pcbi.1013425.ref045","doi-asserted-by":"crossref","DOI":"10.1007\/s11538-021-00938-9","article-title":"Multiscale modeling of uranium bioreduction in porous media by one-dimensional biofilms","volume":"83","author":"HJ Gaebler","year":"2021","journal-title":"Bull Math Biol."},{"key":"pcbi.1013425.ref046","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1742-4682-6-30","article-title":"A modeling and simulation study of siderophore mediated antagonism in dual-species biofilms","volume":"6","author":"HJ Eberl","year":"2009","journal-title":"Theor Biol Med Model."},{"issue":"1","key":"pcbi.1013425.ref047","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s11538-013-9898-2","article-title":"A modeling and simulation study of the role of suspended microbial populations in nitrification in a biofilm reactor","volume":"76","author":"A Ma\u0161i\u0107","year":"2014","journal-title":"Bull Math Biol."},{"issue":"4","key":"pcbi.1013425.ref048","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1007\/s10884-022-10240-4","article-title":"Travelling waves in a PDE-ODE coupled model of cellulolytic biofilms with nonlinear diffusion","volume":"36","author":"K Mitra","year":"2024","journal-title":"J Dyn Differ Equ."},{"issue":"7","key":"pcbi.1013425.ref049","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0132385","article-title":"A mathematical model of quorum sensing induced biofilm detachment","volume":"10","author":"BO Emerenini","year":"2015","journal-title":"PLoS One."},{"issue":"2","key":"pcbi.1013425.ref050","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1137\/18M1234096","article-title":"Multiscale flux-based modeling of biofilm communities","volume":"18","author":"T Zhang","year":"2020","journal-title":"Multiscale Model Simul."},{"key":"pcbi.1013425.ref051","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.mbs.2018.07.009","article-title":"Mathematical modeling of dispersal phenomenon in biofilms","volume":"307","author":"B D\u2019Acunto","year":"2019","journal-title":"Math Biosci."},{"issue":"2","key":"pcbi.1013425.ref052","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s11538-006-9168-7","article-title":"A multidimensional multispecies continuum model for heterogeneous biofilm development","volume":"69","author":"E Alpkvista","year":"2007","journal-title":"Bull Math Biol."},{"key":"pcbi.1013425.ref053","doi-asserted-by":"crossref","first-page":"031902","DOI":"10.1103\/PhysRevE.74.031902","article-title":"Role of cohesion in the material description of biofilms","volume":"74","author":"I Klapper","year":"2006","journal-title":"Phys Rev E Stat Nonlin Soft Matter Phys."},{"issue":"14","key":"pcbi.1013425.ref054","doi-asserted-by":"crossref","first-page":"11577","DOI":"10.3390\/ijms241411577","article-title":"An Overview of the factors involved in biofilm production by the Enterococcus genus","volume":"24","author":"P \u00c8\u02dcchiopu","year":"2023","journal-title":"Int J Mol Sci."},{"key":"pcbi.1013425.ref055","article-title":"Role of extracellular DNA in Enterococcus faecalis biofilm formation and its susceptibility to sodium hypochlorite","volume":"27","author":"M-K Yu","year":"2019","journal-title":"J Appl Oral Sci."},{"key":"pcbi.1013425.ref056","doi-asserted-by":"crossref","first-page":"640129","DOI":"10.3389\/froh.2021.640129","article-title":"Understanding the matrix: the role of extracellular DNA in oral biofilms","volume":"2","author":"HJ Serrage","year":"2021","journal-title":"Front Oral Health."},{"key":"pcbi.1013425.ref057","unstructured":"Sedgewick R, Wayne K. Algorithms. Addison-Wesley Professional; 2011."},{"key":"pcbi.1013425.ref058","unstructured":"Ester M, Kriegel HP, Sander J, Xu X, et al. A density-based algorithm for discovering clusters in large spatial databases with noise. In: KDD. vol. 96. 1996. pp. 226\u2013231."},{"issue":"3","key":"pcbi.1013425.ref059","doi-asserted-by":"crossref","first-page":"112063","DOI":"10.1016\/j.isci.2025.112063","article-title":"Release of extracellular DNA by Pseudomonas sp. as a major determinant for biofilm switching and an early indicator for cell population control","volume":"28","author":"FB Kakahi","year":"2025","journal-title":"iScience."},{"issue":"1","key":"pcbi.1013425.ref060","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41522-022-00278-z","article-title":"Staphylococcus aureus utilizes environmental RNA as a building material in specific polysaccharide-dependent biofilms","volume":"8","author":"A Chiba","year":"2022","journal-title":"NPJ Biofilms Microbiomes."},{"key":"pcbi.1013425.ref061","doi-asserted-by":"crossref","first-page":"36424","DOI":"10.1038\/srep36424","article-title":"Evidence of the presence of nucleic acids and \u03b2-glucan in the matrix of non-typeable Haemophilus influenzae in vitro biofilms","volume":"6","author":"M Domenech","year":"2016","journal-title":"Sci Rep."},{"key":"pcbi.1013425.ref062","doi-asserted-by":"crossref","unstructured":"Scherbakova AE, Rykova VS, Danilova KV, Solovyev AI, Egorova DA. Extracellular RNA isolation from biofilm matrix of Pseudomonas aeruginosa. Bio-Protocol. 2020:e3810.","DOI":"10.21769\/BioProtoc.3810"},{"issue":"1","key":"pcbi.1013425.ref063","doi-asserted-by":"crossref","first-page":"7772","DOI":"10.1038\/s41467-023-43533-3","article-title":"RNA is a key component of extracellular DNA networks in Pseudomonas aeruginosa biofilms","volume":"14","author":"S Mugunthan","year":"2023","journal-title":"Nat Commun."},{"key":"pcbi.1013425.ref064","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1006\/jmbi.1993.1426","article-title":"Erythromycin binding is reduced in ribosomes with conformational alterations in the 23 S rRNA peptidyl","volume":"232","author":"T Loop","year":"1993","journal-title":"J Mol Biol."},{"issue":"9","key":"pcbi.1013425.ref065","doi-asserted-by":"crossref","first-page":"3759","DOI":"10.1128\/IAI.00149-09","article-title":"Further characterization of the epa gene cluster and Epa polysaccharides of Enterococcus faecalis","volume":"77","author":"F Teng","year":"2009","journal-title":"Infect Immun."},{"issue":"19","key":"pcbi.1013425.ref066","doi-asserted-by":"crossref","first-page":"5659","DOI":"10.1128\/JB.183.19.5659-5667.2001","article-title":"Analysis of functional domains of the Enterococcus faecalis pheromone-induced surface protein aggregation substance","volume":"183","author":"CM Waters","year":"2001","journal-title":"J Bacteriol."},{"key":"pcbi.1013425.ref067","unstructured":"Deutsch A, Dormann S. Mathematical modeling of biological pattern formation. Springer; 2005."},{"key":"pcbi.1013425.ref068","unstructured":"Delavar MA, Wang J. Advanced methods and mathematical modeling of biofilms: Applications in health care, medicine, food, aquaculture, environment, and industry. Academic Press; 2022."},{"key":"pcbi.1013425.ref069","doi-asserted-by":"crossref","unstructured":"Ilachinski A. Cellular automata: a discrete universe. World Scientific Publishing Company; 2001.","DOI":"10.1142\/4702"},{"issue":"10","key":"pcbi.1013425.ref070","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0076599","article-title":"Floating ice-algal aggregates below melting arctic sea ice","volume":"8","author":"P Assmy","year":"2013","journal-title":"PLoS One."},{"issue":"14","key":"pcbi.1013425.ref071","doi-asserted-by":"crossref","DOI":"10.1128\/JB.00733-17","article-title":"Mechanistic Features of the Enterococcal pCF10 Sex Pheromone Response and the Biology of Enterococcus faecalis in Its Natural Habitat","volume":"200","author":"RJ Breuer","year":"2018","journal-title":"J Bacteriol."},{"key":"pcbi.1013425.ref072","doi-asserted-by":"crossref","first-page":"580466","DOI":"10.3389\/fmicb.2020.580466","article-title":"Exposure to one antibiotic leads to acquisition of resistance to another antibiotic via quorum sensing mechanisms","volume":"11","author":"C-C Shu","year":"2021","journal-title":"Front Microbiol."},{"issue":"6","key":"pcbi.1013425.ref073","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1002\/path.1700350614","article-title":"A new culture medium for the production of antigenic streptococcal h\u00e6 molysin","volume":"35","author":"EW Todd","year":"1932","journal-title":"J Pathol."},{"issue":"6007","key":"pcbi.1013425.ref074","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1126\/science.1192588","article-title":"Interdependence of cell growth and gene expression: origins and consequences","volume":"330","author":"M Scott","year":"2010","journal-title":"Science."},{"issue":"5","key":"pcbi.1013425.ref075","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1128\/JB.185.5.1485-1491.2003","article-title":"Diffusion in biofilms","volume":"185","author":"PS Stewart","year":"2003","journal-title":"J Bacteriol."},{"key":"pcbi.1013425.ref076","unstructured":"Berg HC. Random walks in biology. Princeton University Press; 1993."},{"issue":"6","key":"pcbi.1013425.ref077","doi-asserted-by":"crossref","first-page":"065005","DOI":"10.1088\/1478-3975\/aa8001","article-title":"Predicting the dynamics of bacterial growth inhibition by ribosome-targeting antibiotics","volume":"14","author":"P Greulich","year":"2017","journal-title":"Phys Biol."},{"issue":"18","key":"pcbi.1013425.ref078","doi-asserted-by":"crossref","DOI":"10.1128\/JB.00253-20","article-title":"Development of a New Bead Movement-Based Computational Framework Shows that Bacterial Amyloid Curli Reduces Bead Mobility in Biofilms","volume":"202","author":"K Malhotra","year":"2020","journal-title":"J Bacteriol."},{"issue":"3","key":"pcbi.1013425.ref079","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/1574-6941.12168","article-title":"Extracellular DNA in adhesion and biofilm formation of four environmental isolates: a quantitative study","volume":"86","author":"L Tang","year":"2013","journal-title":"FEMS Microbiol Ecol."}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1013425","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1013425","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T17:59:04Z","timestamp":1758218344000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1013425"}},"subtitle":[],"editor":[{"given":"Ricardo","family":"Martinez-Garcia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":79,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1013425","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,2]]}}}