{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:54:12Z","timestamp":1792166052638,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011338","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000}}],"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1158678"],"award-info":[{"award-number":["APP1158678"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["FT190100733"],"award-info":[{"award-number":["FT190100733"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["FT180100049"],"award-info":[{"award-number":["FT180100049"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["Erwin Schroedinger Fellowship"],"award-info":[{"award-number":["Erwin Schroedinger Fellowship"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020821","name":"Monash Biomedicine Discovery Institute, Monash University","doi-asserted-by":"publisher","award":["Postgraduate scholarship"],"award-info":[{"award-number":["Postgraduate scholarship"]}],"id":[{"id":"10.13039\/501100020821","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001779","name":"Monash University","doi-asserted-by":"publisher","award":["RTP PhD scholarship"],"award-info":[{"award-number":["RTP PhD scholarship"]}],"id":[{"id":"10.13039\/501100001779","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Fungal pathogens overcome antifungal drug therapy by classic resistance mechanisms, such as increased efflux or changes to the drug target. However, even when a fungal strain is susceptible, trailing or persistent microbial growth in the presence of an antifungal drug can contribute to therapeutic failure. This trailing growth is caused by adaptive physiological changes that enable the growth of a subpopulation of fungal cells in high drug concentrations, in what is described as drug tolerance. Mechanistically, antifungal drug tolerance is incompletely understood. Here we report that the transcriptional activator Rpn4 is important for drug tolerance in the human fungal pathogen\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    . Deletion of\n                    <jats:italic>RPN4<\/jats:italic>\n                    eliminates tolerance to the commonly used antifungal drug fluconazole. We defined the mechanism and show that Rpn4 controls fluconazole tolerance via two target pathways. First, Rpn4 activates proteasome gene expression, which enables sufficient proteasome capacity to overcome fluconazole-induced proteotoxicity and the accumulation of ubiquitinated proteins targeted for degradation. Consistently, inhibition of the proteasome with MG132 eliminates fluconazole tolerance and resistance, and phenocopies the\n                    <jats:italic>rpn4\u0394\/\u0394<\/jats:italic>\n                    mutant for loss of tolerance. Second, Rpn4 is required for wild type expression of the genes required for the synthesis of the membrane lipid ergosterol. Our data indicates that this function of Rpn4 is required for mitigating the inhibition of ergosterol biosynthesis by fluconazole. Based on our findings, we propose that Rpn4 is a central hub for fluconazole tolerance in\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>albicans<\/jats:italic>\n                    by coupling the regulation of protein homeostasis (proteostasis) and lipid metabolism to overcome drug-induced proteotoxicity and membrane stress.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011338","type":"journal-article","created":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T13:33:19Z","timestamp":1681911199000},"page":"e1011338","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["The proteasome regulator Rpn4 controls antifungal drug tolerance by coupling protein homeostasis with metabolic responses to drug stress"],"prefix":"10.1371","volume":"19","author":[{"given":"Ka Pui Sharon","family":"Yau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshini","family":"Weerasinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francios A. B.","family":"Olivier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tricia L.","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Traude H.","family":"Beilharz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6252-3104","authenticated-orcid":true,"given":"Ana","family":"Traven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"issue":"1","key":"ppat.1011338.ref001","doi-asserted-by":"crossref","first-page":"18026","DOI":"10.1038\/nrdp.2018.26","article-title":"Invasive candidiasis.","volume":"4","author":"PG Pappas","year":"2018","journal-title":"Nature Reviews Disease Primers"},{"issue":"1","key":"ppat.1011338.ref002","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.idc.2015.10.012","article-title":"Antifungal Agents: Spectrum of Activity, Pharmacology, and Clinical Indications.","volume":"30","author":"JE Nett","year":"2016","journal-title":"Infect Dis Clin North Am."},{"issue":"15","key":"ppat.1011338.ref003","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1007\/s40265-021-01611-0","article-title":"The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.","volume":"81","author":"M Hoenigl","year":"2021","journal-title":"Drugs"},{"issue":"6","key":"ppat.1011338.ref004","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41579-019-0322-2","article-title":"Drug resistance and tolerance in fungi.","volume":"18","author":"J Berman","year":"2020","journal-title":"Nat Rev Microbiol"},{"key":"ppat.1011338.ref005","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.drup.2015.10.001","article-title":"Defining the frontiers between antifungal resistance, tolerance and the concept of persistence","volume":"23","author":"E Delarze","year":"2015","journal-title":"Drug Resist Updat"},{"issue":"12","key":"ppat.1011338.ref006","article-title":"Implications of the EUCAST Trailing Phenomenon in Candida tropicalis for the In Vivo Susceptibility in Invertebrate and Murine Models","volume":"62","author":"KMT Astvad","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"ppat.1011338.ref007","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/myc.13191","article-title":"Impact of tolerance to fluconazole on treatment response in Candida albicans bloodstream infection.","volume":"64","author":"T Levinson","year":"2021","journal-title":"Mycoses."},{"issue":"1","key":"ppat.1011338.ref008","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1038\/s41467-018-04926-x","article-title":"Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia.","volume":"9","author":"A Rosenberg","year":"2018","journal-title":"Nat Commun."},{"issue":"1","key":"ppat.1011338.ref009","doi-asserted-by":"crossref","first-page":"4495","DOI":"10.1038\/s41467-018-06944-1","article-title":"Candida albicans gains azole resistance by altering sphingolipid composition.","volume":"9","author":"J Gao","year":"2018","journal-title":"Nat Commun."},{"issue":"10","key":"ppat.1011338.ref010","doi-asserted-by":"crossref","first-page":"6060","DOI":"10.1128\/AAC.00732-16","article-title":"The RTA3 Gene, Encoding a Putative Lipid Translocase, Influences the Susceptibility of Candida albicans to Fluconazole","volume":"60","author":"SG Whaley","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"ppat.1011338.ref011","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1046\/j.1365-2958.2003.03495.x","article-title":"Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence","volume":"48","author":"D Sanglard","year":"2003","journal-title":"Mol Microbiol"},{"issue":"12","key":"ppat.1011338.ref012","doi-asserted-by":"crossref","first-page":"7330","DOI":"10.1128\/IAI.72.12.7330-7333.2004","article-title":"The calcineurin target, Crz1, functions in azole tolerance but is not required for virulence of Candida albicans","volume":"72","author":"C Onyewu","year":"2004","journal-title":"Infect Immun"},{"issue":"5744","key":"ppat.1011338.ref013","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1126\/science.1118370","article-title":"Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi","volume":"309","author":"LE Cowen","year":"2005","journal-title":"Science"},{"issue":"2","key":"ppat.1011338.ref014","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1074\/jbc.M117.807032","article-title":"Azole resistance in a Candida albicans mutant lacking the ABC transporter CDR6\/ROA1 depends on TOR signaling","volume":"293","author":"NK Khandelwal","year":"2018","journal-title":"J Biol Chem"},{"issue":"1\u20132","key":"ppat.1011338.ref015","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0014-5793(99)00467-6","article-title":"Rpn4p acts as a transcription factor by binding to PACE, a nonamer box found upstream of 26S proteasomal and other genes in yeast","volume":"450","author":"G Mannhaupt","year":"1999","journal-title":"FEBS Lett"},{"issue":"2","key":"ppat.1011338.ref016","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1091\/mbc.e05-06-0501","article-title":"Role of the Hog1 stress-activated protein kinase in the global transcriptional response to stress in the fungal pathogen Candida albicans","volume":"17","author":"B Enjalbert","year":"2006","journal-title":"Mol Biol Cell"},{"issue":"2","key":"ppat.1011338.ref017","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/nrmicro.2016.157","article-title":"Candida albicans cell-type switching and functional plasticity in the mammalian host","volume":"15","author":"SM Noble","year":"2017","journal-title":"Nat Rev Microbiol"},{"issue":"12","key":"ppat.1011338.ref018","doi-asserted-by":"crossref","first-page":"111374","DOI":"10.1016\/j.celrep.2022.111374","article-title":"The escape of Candida albicans from macrophages is enabled by the fungal toxin candidalysin and two host cell death pathways","volume":"40","author":"FAB Olivier","year":"2022","journal-title":"Cell Rep"},{"issue":"1","key":"ppat.1011338.ref019","doi-asserted-by":"crossref","first-page":"6699","DOI":"10.1038\/s41467-021-27034-9","article-title":"Inflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages.","volume":"12","author":"X Ding","year":"2021","journal-title":"Nat Commun."},{"issue":"5","key":"ppat.1011338.ref020","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S0092-8674(00)80358-X","article-title":"Nonfilamentous C. albicans mutants are avirulent","volume":"90","author":"HJ Lo","year":"1997","journal-title":"Cell"},{"issue":"5","key":"ppat.1011338.ref021","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.cmet.2018.03.019","article-title":"Glucose Homeostasis Is Important for Immune Cell Viability during Candida Challenge and Host Survival of Systemic Fungal Infection","volume":"27","author":"TM Tucey","year":"2018","journal-title":"Cell Metab"},{"issue":"12","key":"ppat.1011338.ref022","doi-asserted-by":"crossref","first-page":"e1000783","DOI":"10.1371\/journal.pgen.1000783","article-title":"A phenotypic profile of the Candida albicans regulatory network.","volume":"5","author":"OR Homann","year":"2009","journal-title":"PLoS Genet."},{"issue":"11","key":"ppat.1011338.ref023","doi-asserted-by":"crossref","first-page":"6807","DOI":"10.1128\/AAC.00064-14","article-title":"Disruption of the transcriptional regulator Cas5 results in enhanced killing of Candida albicans by Fluconazole","volume":"58","author":"EM Vasicek","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"ppat.1011338.ref024","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1099\/mic.0.000295","article-title":"diskImageR: quantification of resistance and tolerance to antimicrobial drugs using disk diffusion assays","volume":"162","author":"AC Gerstein","year":"2016","journal-title":"Microbiology (Reading)."},{"issue":"6","key":"ppat.1011338.ref025","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1073\/pnas.071022298","article-title":"RPN4 is a ligand, substrate, and transcriptional regulator of the 26S proteasome: a negative feedback circuit","volume":"98","author":"Y Xie","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"ppat.1011338.ref026","article-title":"Susceptibility to Medium-Chain Fatty Acids Is Associated with Trisomy of Chromosome 7 in Candida albicans.","volume":"4","author":"Q Ma","year":"2019","journal-title":"mSphere"},{"issue":"7","key":"ppat.1011338.ref027","doi-asserted-by":"crossref","DOI":"10.3390\/genes11070795","article-title":"Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae.","volume":"11","author":"T Jord\u00e1","year":"2020","journal-title":"Genes (Basel)."},{"issue":"3","key":"ppat.1011338.ref028","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1091\/mbc.e12-01-0065","article-title":"A genome-wide transcriptional analysis of morphology determination in Candida albicans","volume":"24","author":"PL Carlisle","year":"2013","journal-title":"Mol Biol Cell"},{"issue":"12","key":"ppat.1011338.ref029","doi-asserted-by":"crossref","first-page":"e398","DOI":"10.1371\/journal.pbio.0020398","article-title":"Conservation and evolution of cis-regulatory systems in ascomycete fungi","volume":"2","author":"AP Gasch","year":"2004","journal-title":"PLoS Biol"},{"key":"ppat.1011338.ref030","doi-asserted-by":"crossref","first-page":"6741","DOI":"10.1038\/ncomms7741","article-title":"Global analysis of fungal morphology exposes mechanisms of host cell escape","volume":"6","author":"TR O\u2019Meara","year":"2015","journal-title":"Nat Commun"},{"issue":"5","key":"ppat.1011338.ref031","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1128\/EC.00345-12","article-title":"Comparison of sterol import under aerobic and anaerobic conditions in three fungal species, Candida albicans, Candida glabrata, and Saccharomyces cerevisiae","volume":"12","author":"M Zavrel","year":"2013","journal-title":"Eukaryot Cell"},{"issue":"6","key":"ppat.1011338.ref032","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1111\/j.1365-2958.2011.07542.x","article-title":"Molecular and proteomic analyses highlight the importance of ubiquitination for the stress resistance, metabolic adaptation, morphogenetic regulation and virulence of Candida albicans","volume":"79","author":"MD Leach","year":"2011","journal-title":"Mol Microbiol"},{"issue":"9","key":"ppat.1011338.ref033","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00554-20","article-title":"Candida glabrata Transcription Factor Rpn4 Mediates Fluconazole Resistance through Regulation of Ergosterol Biosynthesis and Plasma Membrane Permeability","volume":"64","author":"P Pais","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"ppat.1011338.ref034","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/msb.2010.107","article-title":"Cross-species chemogenomic profiling reveals evolutionarily conserved drug mode of action","volume":"6","author":"L Kapitzky","year":"2010","journal-title":"Mol Syst Biol"},{"issue":"1","key":"ppat.1011338.ref035","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/nbt919","article-title":"Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways","volume":"22","author":"AB Parsons","year":"2004","journal-title":"Nat Biotechnol"},{"key":"ppat.1011338.ref036","doi-asserted-by":"crossref","first-page":"591140","DOI":"10.3389\/fmicb.2020.591140","article-title":"Identification and Characterization of Mediators of Fluconazole Tolerance in Candida albicans.","volume":"11","author":"E Delarze","year":"2020","journal-title":"Front Microbiol."},{"issue":"11","key":"ppat.1011338.ref037","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1074\/mcp.RA120.002050","article-title":"The Capture of a Disabled Proteasome Identifies Erg25 as a Substrate for Endoplasmic Reticulum Associated Degradation","volume":"19","author":"TM Buck","year":"2020","journal-title":"Mol Cell Proteomics"},{"key":"ppat.1011338.ref038","doi-asserted-by":"crossref","first-page":"100348","DOI":"10.1016\/j.jbc.2021.100348","article-title":"Deubiquitinase Ubp3 enhances the proteasomal degradation of key enzymes in sterol homeostasis","volume":"296","author":"Q Lan","year":"2021","journal-title":"J Biol Chem"},{"key":"ppat.1011338.ref039","doi-asserted-by":"crossref","first-page":"e00953","DOI":"10.7554\/eLife.00953","article-title":"Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10\/Teb4.","volume":"2","author":"O Foresti","year":"2013","journal-title":"Elife"},{"key":"ppat.1011338.ref040","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.43244","article-title":"The proteasome biogenesis regulator Rpn4 cooperates with the unfolded protein response to promote ER stress resistance.","volume":"8","author":"RM Schmidt","year":"2019","journal-title":"Elife"},{"issue":"1","key":"ppat.1011338.ref041","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s12038-010-0014-6","article-title":"The Fungal Genetics Stock Center: a repository for 50 years of fungal genetics research","volume":"35","author":"K McCluskey","year":"2010","journal-title":"J Biosci"},{"issue":"2","key":"ppat.1011338.ref042","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1128\/EC.4.2.298-309.2005","article-title":"Strains and strategies for large-scale gene deletion studies of the diploid human fungal pathogen Candida albicans","volume":"4","author":"SM Noble","year":"2005","journal-title":"Eukaryot Cell"},{"key":"ppat.1011338.ref043","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1186\/1471-2164-9-578","article-title":"A toolbox for epitope-tagging and genome-wide location analysis in Candida albicans","volume":"9","author":"H Lavoie","year":"2008","journal-title":"BMC Genomics"},{"issue":"8","key":"ppat.1011338.ref044","doi-asserted-by":"crossref","first-page":"e1008695","DOI":"10.1371\/journal.ppat.1008695","article-title":"Metabolic competition between host and pathogen dictates inflammasome responses to fungal infection.","volume":"16","author":"TM Tucey","year":"2020","journal-title":"PLoS Pathog."},{"issue":"7","key":"ppat.1011338.ref045","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis.","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat Methods."},{"issue":"8","key":"ppat.1011338.ref046","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1016\/j.celrep.2018.10.080","article-title":"A Metabolic Checkpoint for the Yeast-to-Hyphae Developmental Switch Regulated by Endogenous Nitric Oxide Signaling.","volume":"25","author":"B Koch","year":"2018","journal-title":"Cell Rep"},{"issue":"6","key":"ppat.1011338.ref047","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/gkp045","article-title":"Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data","volume":"37","author":"JM Ruijter","year":"2009","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"ppat.1011338.ref048","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0014-5793(98)00084-2","article-title":"Son1p is a component of the 26S proteasome of the yeast Saccharomyces cerevisiae","volume":"423","author":"M Fujimuro","year":"1998","journal-title":"FEBS Lett"},{"issue":"8","key":"ppat.1011338.ref049","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1261\/rna.048355.114","article-title":"PAT-seq: a method to study the integration of 3\u2019-UTR dynamics with gene expression in the eukaryotic transcriptome","volume":"21","author":"PF Harrison","year":"2015","journal-title":"Rna"},{"issue":"11","key":"ppat.1011338.ref050","first-page":"100","article-title":"YMAP: a pipeline for visualization of copy number variation and loss of heterozygosity in eukaryotic pathogens","volume":"6","author":"DA Abbey","year":"2014","journal-title":"Genome Med"},{"issue":"3","key":"ppat.1011338.ref051","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/gb-2010-11-3-r25","article-title":"A scaling normalization method for differential expression analysis of RNA-seq data","volume":"11","author":"MD Robinson","year":"2010","journal-title":"Genome Biol"},{"issue":"2","key":"ppat.1011338.ref052","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1186\/gb-2014-15-2-r29","article-title":"voom: Precision weights unlock linear model analysis tools for RNA-seq read counts","volume":"15","author":"CW Law","year":"2014","journal-title":"Genome Biol"},{"key":"ppat.1011338.ref053","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 Bioinformatics"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1011338","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011338","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T13:31:57Z","timestamp":1682947917000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011338"}},"subtitle":[],"editor":[{"given":"Aaron P.","family":"Mitchell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,4,19]]},"references-count":53,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011338","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,19]]}}}