{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T19:05:12Z","timestamp":1782587112473,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011865","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000}}],"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM057089"],"award-info":[{"award-number":["R01GM057089"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2020-06325"],"award-info":[{"award-number":["RGPIN-2020-06325"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","award":["OGI-207"],"award-info":[{"award-number":["OGI-207"]}],"id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013873","name":"Government of Ontario","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013873","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centre for advanced computing"},{"name":"Compute Ontario"},{"DOI":"10.13039\/501100021202","name":"Digital Research Alliance of Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100021202","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Generalist microbes have adapted to a multitude of environmental stresses through their integrated stress response system. Individual stress responses have been quantified by <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> metabolism and expression (ME) models under thermal, oxidative and acid stress, respectively. However, the systematic quantification of cross-stress &amp; cross-talk among these stress responses remains lacking. Here, we present StressME: the unified stress response model of <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> combining thermal (FoldME), oxidative (OxidizeME) and acid (AcidifyME) stress responses. StressME is the most up to date ME model for <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> and it reproduces all published single-stress ME models. Additionally, it includes refined rate constants to improve prediction accuracy for wild-type and stress-evolved strains. StressME revealed certain optimal proteome allocation strategies associated with cross-stress and cross-talk responses. These stress-optimal proteomes were shaped by trade-offs between protective vs. metabolic enzymes; cytoplasmic vs. periplasmic chaperones; and expression of stress-specific proteins. As StressME is tuned to compute metabolic and gene expression responses under mild acid, oxidative, and thermal stresses, it is useful for engineering and health applications. The modular design of our open-source package also facilitates model expansion (e.g., to new stress mechanisms) by the computational biology community.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1011865","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T18:36:58Z","timestamp":1707763018000},"page":"e1011865","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["StressME: Unified computing framework of Escherichia coli metabolism, gene expression, and stress responses"],"prefix":"10.1371","volume":"20","author":[{"given":"Jiao","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2357-6785","authenticated-orcid":true,"given":"Bernhard 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plasma treatments.","volume":"103","author":"JH Cheng","year":"2020","journal-title":"Trends in Food Science & Technology."},{"key":"pcbi.1011865.ref016","doi-asserted-by":"crossref","first-page":"103388","DOI":"10.1016\/j.fm.2019.103388","article-title":"Combination of mild heat and plant essential oil constituents to inactivate resistant variants of Escherichia coli in buffer and in coconut water.","volume":"87","author":"E Gayan","year":"2020","journal-title":"Food Microbiol."},{"issue":"2","key":"pcbi.1011865.ref017","doi-asserted-by":"crossref","DOI":"10.1002\/2688-8319.12027","article-title":"Preparing for the worst: Utilizing stress-tolerant soil microbial communities to aid ecological restoration in the Anthropocene.","volume":"1","author":"JM Valliere","year":"2020","journal-title":"Ecological Solutions and Evidence."},{"key":"pcbi.1011865.ref018","doi-asserted-by":"crossref","first-page":"888746","DOI":"10.3389\/fmicb.2022.888746","article-title":"Microbial Adaptation to 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Kuzuyama","year":"2000","journal-title":"J Biol Chem"},{"issue":"1","key":"pcbi.1011865.ref022","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nbt.3418","article-title":"The quantitative and condition-dependent Escherichia coli proteome","volume":"34","author":"A Schmidt","year":"2016","journal-title":"Nat Biotechnol"},{"issue":"1","key":"pcbi.1011865.ref023","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/metabo4010001","article-title":"Regulation Systems of Bacteria such as Escherichia coli in Response to Nutrient Limitation and Environmental Stresses.","volume":"4","author":"K. Shimizu","year":"2013","journal-title":"Metabolites."},{"issue":"2","key":"pcbi.1011865.ref024","article-title":"Mechanisms, Detection, and Relevance of Protein Acetylation in Prokaryotes.","volume":"10","author":"DG Christensen","year":"2019"},{"issue":"2","key":"pcbi.1011865.ref025","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s12192-016-0667-7","article-title":"Cross-stress resistance in Saccharomyces cerevisiae yeast-new insight into an old phenomenon","volume":"21","author":"A. Swiecilo","year":"2016","journal-title":"Cell Stress & Chaperones"},{"issue":"3","key":"pcbi.1011865.ref026","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0168-1605(98)00089-0","article-title":"Modification of Saccharomyces cerevisiae thermotolerance following rapid exposure to acid stress","volume":"42","author":"V Carmelo","year":"1998","journal-title":"International Journal of Food Microbiology"},{"key":"pcbi.1011865.ref027","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1099\/00221287-137-7-1701","article-title":"Induction of increased thermotolerance in saccharomyces-cerevisiae may be triggered by a mechanism involving intracellular pH","volume":"137","author":"PJ Coote","year":"1991","journal-title":"Journal of General Microbiology"},{"issue":"4","key":"pcbi.1011865.ref028","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1046\/j.1365-2958.1996.561412.x","article-title":"New components of protein folding in extracytoplasmic compartments of Escherichia coli SurA, FkpA and Skp\/OmpH","volume":"21","author":"D Missiakas","year":"1996","journal-title":"Mol Microbiol"},{"issue":"1","key":"pcbi.1011865.ref029","doi-asserted-by":"crossref","first-page":"e0262450","DOI":"10.1371\/journal.pone.0262450","article-title":"Experimental determination of Escherichia coli biomass composition for constraint-based metabolic modeling.","volume":"17","author":"V Simensen","year":"2022","journal-title":"PLoS One.PubMed Central PMCID"},{"issue":"8","key":"pcbi.1011865.ref030","doi-asserted-by":"crossref","first-page":"e0202565","DOI":"10.1371\/journal.pone.0202565","article-title":"A low-complexity metabolic network model for the respiratory and fermentative metabolism of Escherichia coli","volume":"13","author":"I Tack","year":"2018","journal-title":"PLoS One"},{"issue":"4","key":"pcbi.1011865.ref031","first-page":"383","article-title":"A radical-chemical route to acetyl-CoA: the anaerobically induced pyruvate formate-lyase system of Escherichia coli","volume":"6","author":"J Knappe","year":"1990","journal-title":"FEMS Microbiol Rev"},{"issue":"1","key":"pcbi.1011865.ref032","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0003-9861(84)90054-7","article-title":"Pyruvate formate-lyase (inactive form) and pyruvate formate-lyase activating enzyme of Escherichia coli: isolation and structural properties","volume":"228","author":"H Conradt","year":"1984","journal-title":"Arch Biochem Biophys"},{"key":"pcbi.1011865.ref033","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ymben.2023.04.009","article-title":"Evaluating proteome allocation of Saccharomyces cerevisiae phenotypes with resource balance analysis","volume":"77","author":"HV Dinh","year":"2023","journal-title":"Metab Eng"},{"issue":"9","key":"pcbi.1011865.ref034","doi-asserted-by":"crossref","first-page":"5723","DOI":"10.1074\/jbc.M113.496877","article-title":"Pyruvate formate-lyase and its activation by pyruvate formate-lyase activating enzyme","volume":"289","author":"AV Crain","year":"2014","journal-title":"J Biol Chem"},{"issue":"7580","key":"pcbi.1011865.ref035","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature15765","article-title":"Overflow metabolism in Escherichia coli results from efficient proteome allocation","volume":"528","author":"M Basan","year":"2015","journal-title":"Nature"},{"key":"pcbi.1011865.ref036","doi-asserted-by":"crossref","first-page":"36734","DOI":"10.1038\/srep36734","article-title":"Principles of proteome allocation are revealed using proteomic data and genome-scale models.","volume":"6","author":"L Yang","year":"2016","journal-title":"Sci Rep."}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1011865","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011865","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T19:19:03Z","timestamp":1708715943000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011865"}},"subtitle":[],"editor":[{"given":"Arturo","family":"Medrano-Soto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,12]]},"references-count":36,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1011865","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1011865","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,12]]}}}