{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:42:19Z","timestamp":1788496939060,"version":"build-2803163510"},"reference-count":135,"publisher":"Microbiology Society","issue":"2","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,1]]},"abstract":"<jats:p>\n                    Our previous work demonstrated that two commonly used fluorescent dyes that were accumulated by wild-type\n                    <jats:italic>\n                      <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.3093\" xlink:type=\"simple\">Escherichia coli<\/jats:ext-link>\n                      <\/jats:named-content>\n                    <\/jats:italic>\n                    MG1655 were differentially transported in single-gene knockout strains, and also that they might be used as surrogates in flow cytometric transporter assays. We summarize the desirable properties of such stains, and here survey 143 candidate dyes. We eventually triage them (on the basis of signal, accumulation levels and cost) to a palette of 39 commercially available and affordable fluorophores that are accumulated significantly by wild-type cells of the \u2018Keio\u2019 strain BW25113, as measured flow cytometrically. Cheminformatic analyses indicate both their similarities and their (much more considerable) structural differences. We describe the effects of pH and of the efflux pump inhibitor chlorpromazine on the accumulation of the dyes. Even the \u2018wild-type\u2019 MG1655 and BW25113 strains can differ significantly in their ability to take up such dyes. We illustrate the highly differential uptake of our dyes into strains with particular lesions in, or overexpressed levels of, three particular transporters or transporter components (\n                    <jats:italic>yhjV<\/jats:italic>\n                    ,\n                    <jats:italic>yihN<\/jats:italic>\n                    and\n                    <jats:italic>tolC<\/jats:italic>\n                    ). The relatively small collection of dyes described offers a rapid, inexpensive, convenient and informative approach to the assessment of microbial physiology and phenotyping of membrane transporter function.\n                  <\/jats:p>","DOI":"10.1099\/mic.0.001016","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T13:18:14Z","timestamp":1609939094000},"source":"Crossref","is-referenced-by-count":15,"title":["A palette of fluorophores that are differentially accumulated by wild-type and mutant strains of Escherichia coli: surrogate ligands for profiling bacterial membrane transporters"],"prefix":"10.1099","volume":"167","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8756-0080","authenticated-orcid":false,"given":"Jesus Enrique","family":"Salcedo-Sora","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Crown St, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3376-7569","authenticated-orcid":false,"given":"Srijan","family":"Jindal","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Crown St, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6235-5462","authenticated-orcid":false,"given":"Steve","family":"O'Hagan","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Manchester Institute of Biotechnology, The University of Manchester, 131 Princess St, Manchester M1 7DN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5838-7963","authenticated-orcid":false,"given":"Douglas B.","family":"Kell","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet, 2800 Kgs Lyngby, Denmark"},{"name":"Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Crown St, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5331.1453"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz030"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(98)80074-2"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.022"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01011"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1128\/MR.60.4.641-696.1996"},{"key":"R7","doi-asserted-by":"crossref","DOI":"10.1002\/0471722731","volume-title":"Practical Flow Cytometry","author":"Shapiro","year":"2003"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20702"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/j.mimet.2013.05.007"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-113-2-369"},{"key":"R11","first-page":"441","article-title":"The application of flow cytometry to the estimation of bacterial antibiotic susceptibility","volume":"36","author":"Mason","year":"1995","journal-title":"J Antibiotic Chemother"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7012(00)00181-0"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/461941"},{"key":"R14","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s11426-015-5518-3","article-title":"Applications and challenges for single-bacteria analysis by flow cytometry","volume":"59","author":"LN","year":"2016","journal-title":"Sci China Chem"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/j.watres.2018.08.013"},{"key":"R16","article-title":"Discriminating bacterial phenotypes at the population and single-cell level: a comparison of flow cytometry and Raman spectroscopy fingerprinting","author":"Garc\u00eda-Timermans","year":"2019","journal-title":"Cytometry A"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.22931"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04366-7"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.000777"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-019-1561-0"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1038\/msb4100050"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2009.92"},{"key":"R23","article-title":"A protet-based, protonic charge transfer model of energy coupling in oxidative and photosynthetic phosphorylation","author":"Kell","year":"2020","journal-title":"OSF preprint"},{"key":"R24","first-page":"429","volume-title":"Bacterial Energy Transduction","author":"Kell","year":"1988"},{"key":"R25","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/B978-0-12-152833-1.50021-6","article-title":"The protonmotive force as an intermediate in electron transport-linked phosphorylation: problems and prospects","volume":"33","author":"Kell","year":"1992","journal-title":"Curr Top Cell Reg"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2438"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2011.05.010"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2012.11.008"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00231"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2014.10.005"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.3762\/bmag.5"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0520-5"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00620-10"},{"key":"R34","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/978-1-60327-545-3_11","article-title":"High-content screening: flow cytometry analysis","volume":"486","author":"Edwards","year":"2009","journal-title":"Methods Mol Biol"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1089\/adt.2007.107"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2013.02.018"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05112-14"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2015.06.006"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.5599\/admet.5.2.376"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2019.01.006"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1038\/ng881"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914771107"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13483-w"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1077"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-006-0037-z"},{"key":"R46","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-84858-7","volume-title":"The Elements of Statistical Learning: Data mining, Inference and Prediction","author":"Hastie","year":"2009"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1016\/0165-022X(80)90013-5"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2728(78)90136-6"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1021\/ci00057a005"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-014-0733-z"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1002\/widm.26"},{"key":"R52","doi-asserted-by":"crossref","DOI":"10.1002\/9783527618279","volume-title":"Handbook of Chemoinformatics: From Data to Knowledge","author":"Gasteiger","year":"2003"},{"key":"R53","volume-title":"Computational Approaches in Cheminformatics and Bioinformatics","author":"Guha","year":"2012"},{"key":"R54","doi-asserted-by":"crossref","DOI":"10.1002\/9783527628766","volume-title":"Molecular Descriptors for Cheminformatics","author":"Todeschini","year":"2009"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.2174\/1570193X14666170518130008"},{"key":"R56","doi-asserted-by":"publisher","DOI":"10.1021\/ci100010v"},{"key":"R57","doi-asserted-by":"publisher","DOI":"10.1002\/minf.201300021"},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-5-26"},{"key":"R59","doi-asserted-by":"publisher","DOI":"10.1186\/s13321-016-0148-0"},{"key":"R60","doi-asserted-by":"publisher","DOI":"10.1039\/c3tc31130a"},{"key":"R61","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00661-08"},{"key":"R62","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt069"},{"key":"R63","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt420"},{"key":"R64","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-1-4471-2017-9_4","volume-title":"Flow Cytometry in Microbiology","author":"Davey","year":"1993"},{"key":"R65","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3380"},{"key":"R66","volume-title":"Efflux-mediated Antimicrobial Resistance in Bacteria: Mechanisms, Regulation and Clinical Implications","author":"X-Z","year":"2016"},{"key":"R67","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1093\/jac\/dkz370","article-title":"2019 Garrod Lecture: MDR efflux in Gram-negative bacteria-how understanding resistance led to a new tool for drug discovery","volume":"74","author":"The","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"R68","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2018.02.006"},{"key":"R69","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2017.09.006"},{"key":"R70","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-016-2190-5"},{"key":"R71","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00587"},{"key":"R72","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-018-4816-5"},{"key":"R73","doi-asserted-by":"crossref","DOI":"10.1128\/AEM.02792-18","article-title":"Experimental evolution of Escherichia coli K-12 in the Presence of Proton Motive Force (PMF) uncoupler carbonyl cyanide m-Chlorophenylhydrazone selects for mutations affecting PMF-driven drug efflux pumps","volume":"85","author":"Griffith","year":"2019","journal-title":"Appl Environ Microbiol"},{"key":"R74","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2015.02.001"},{"key":"R75","first-page":"117","volume-title":"Fermentation Microbiology and Biotechnology","author":"Kell","year":"2019"},{"key":"R76","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)01125-6"},{"key":"R77","doi-asserted-by":"publisher","DOI":"10.1038\/nature13205"},{"key":"R78","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12143"},{"key":"R79","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00189"},{"key":"R80","doi-asserted-by":"crossref","DOI":"10.1016\/j.resmic.2018.02.002","article-title":"Trans-envelope multidrug efflux pumps of Gram-negative bacteria and their synergism with the outer membrane barrier","author":"Zgurskaya","year":"2018","journal-title":"Res Microbiol"},{"key":"R81","doi-asserted-by":"publisher","DOI":"10.1038\/srep21909"},{"key":"R82","doi-asserted-by":"publisher","DOI":"10.1128\/JB.94.4.1112-1123.1967"},{"key":"R83","doi-asserted-by":"publisher","DOI":"10.1128\/JB.150.3.1016-1023.1982"},{"key":"R84","doi-asserted-by":"publisher","DOI":"10.1093\/dnares\/dsi012"},{"key":"R85","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/978-1-4939-2398-4_4","article-title":"Identification of essential genes and synthetic lethal gene combinations in Escherichia coli K-12","volume":"1279","author":"Mori","year":"2015","journal-title":"Methods Mol Biol"},{"key":"R86","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033253"},{"key":"R87","first-page":"293","article-title":"High-Throughput flow cytometry screening of multidrug efflux systems","volume":"2018","author":"Haynes","year":"1700","journal-title":"Methods Mol Biol"},{"key":"R88","article-title":"Structural similarities between some common fluorophores used in biology and marketed drugs, endogenous metabolites, and natural products","volume":"834325","author":"O'Hagan","year":"2019","journal-title":"bioRxiv"},{"key":"R89","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025096930604"},{"key":"R90","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.990170405"},{"key":"R91","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7012(98)00118-3"},{"key":"R92","doi-asserted-by":"publisher","DOI":"10.1021\/bi00713a022"},{"key":"R93","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2016.00029"},{"key":"R94","doi-asserted-by":"publisher","DOI":"10.1016\/1011-1344(90)85037-W"},{"key":"R95","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gnh101"},{"key":"R96","doi-asserted-by":"publisher","DOI":"10.1016\/j.mimet.2016.10.022"},{"key":"R97","doi-asserted-by":"publisher","DOI":"10.1016\/j.watres.2017.01.065"},{"key":"R98","doi-asserted-by":"publisher","DOI":"10.3354\/ame014113"},{"key":"R99","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.6"},{"key":"R100","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.67.10.4662-4670.2001"},{"key":"R101","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-016-1438-0"},{"key":"R102","doi-asserted-by":"publisher","DOI":"10.1007\/s10895-012-1059-8"},{"key":"R103","volume-title":"Chemoinformatics for Drug Discovery","author":"Bajorath","year":"2014"},{"key":"R104","volume-title":"Chemoinformatics: Theory, Practice and Products","author":"Bunin","year":"2007"},{"key":"R105","doi-asserted-by":"crossref","DOI":"10.1201\/9781420082999","volume-title":"Handbook of Chemoinformatics Algorithms","author":"Faulon","year":"2010"},{"key":"R106","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4020-6291-9","volume-title":"An Introduction to Chemoinformatics","author":"Leach","year":"2007"},{"key":"R107","volume-title":"Chemoinformatics in Drug Discovery","author":"Oprea","year":"2004"},{"key":"R108","doi-asserted-by":"publisher","DOI":"10.1039\/b409813g"},{"key":"R109","first-page":"7","article-title":"Introduction to similarity searching in chemistry","volume":"51","author":"Monev","year":"2004","journal-title":"MATCH-Commun Math Comput Chem"},{"key":"R110","doi-asserted-by":"publisher","DOI":"10.1002\/minf.201400024"},{"key":"R111","doi-asserted-by":"publisher","DOI":"10.1007\/s11030-006-9042-4"},{"key":"R112","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.24423"},{"key":"R113","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00266"},{"key":"R114","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201700503"},{"key":"R115","doi-asserted-by":"publisher","DOI":"10.1016\/0167-7799(94)90021-3"},{"key":"R116","doi-asserted-by":"publisher","DOI":"10.1128\/genomeA.01038-14"},{"key":"R117","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.07.015"},{"key":"R118","doi-asserted-by":"publisher","DOI":"10.1186\/s12918-017-0494-1"},{"key":"R119","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2016.10.001"},{"key":"R120","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1097"},{"key":"R121","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1103"},{"key":"R122","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.2.587-598.2006"},{"key":"R123","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2014.972328"},{"key":"R124","doi-asserted-by":"publisher","DOI":"10.2174\/1874285801307010022"},{"key":"R125","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2015-0150"},{"key":"R126","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2017.10.005"},{"key":"R127","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10054"},{"key":"R128","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.11.052"},{"key":"R129","doi-asserted-by":"publisher","DOI":"10.1385\/0-89603-321-X:317"},{"key":"R130","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1900287116"},{"key":"R131","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2672.1992.tb01854.x"},{"key":"R132","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.64.7.2681-2685.1998"},{"key":"R133","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/protein\/gzu029","article-title":"SpeedyGenes: a novel approach for the efficient production of error-corrected, synthetic gene libraries","volume":"27","author":"Currin","year":"2014","journal-title":"Protein Eng Design Sel"},{"key":"R134","doi-asserted-by":"publisher","DOI":"10.1039\/C4CS00351A"},{"key":"R135","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.9b00063"}],"container-title":["Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/micro\/10.1099\/mic.0.001016?crawler=true&mimetype=application\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T17:31:01Z","timestamp":1702575061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/micro\/10.1099\/mic.0.001016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,1]]},"references-count":135,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2,1]]}},"URL":"https:\/\/doi.org\/10.1099\/mic.0.001016","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.06.15.152629","asserted-by":"object"}]},"ISSN":["1350-0872","1465-2080"],"issn-type":[{"value":"1350-0872","type":"print"},{"value":"1465-2080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,1]]}}}