{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T11:47:21Z","timestamp":1768823241274,"version":"3.49.0"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>In this study, we show that a chemical dye, malachite green (MG), which is commonly used in the fish industry as an antifungal, antiparasitic, and antibacterial agent, could effectively kill<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida albicans<\/jats:named-content>and non-<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>species. We have demonstrated that<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>cells are susceptible to MG at a very low concentration (MIC that reduces growth by 50% [MIC<jats:sub>50<\/jats:sub>], 100 ng ml<jats:sup>\u22121<\/jats:sup>) and that the effect of MG is independent of known antifungal targets, such as ergosterol metabolism and major drug efflux pump proteins. Transcriptional profiling in response to MG treatment of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>cells revealed that of a total of 207 responsive genes, 167 genes involved in oxidative stress, virulence, carbohydrate metabolism, heat shock, amino acid metabolism, etc., were upregulated, while 37 genes involved in iron acquisition, filamentous growth, mitochondrial respiration, etc., were downregulated. We confirmed experimentally that<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>cells exposed to MG resort to a fermentative mode of metabolism, perhaps due to defective respiration. In addition, we showed that MG triggers depletion of intracellular iron pools and enhances reactive oxygen species (ROS) levels. These effects could be reversed by the addition of iron or antioxidants, respectively. We provided evidence that the antifungal effect of MG is exerted through the transcription regulators<jats:italic>UPC2<\/jats:italic>(regulating ergosterol biosynthesis and azole resistance) and<jats:italic>STP2<\/jats:italic>(regulating amino acid permease genes). Taken together, our transcriptome, genetic, and biochemical results allowed us to decipher the multiple mechanisms by which MG exerts its anti-<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>effects, leading to a metabolic shift toward fermentation, increased generation of ROS, labile iron deprivation, and cell necrosis.<\/jats:p>","DOI":"10.1128\/aac.00574-11","type":"journal-article","created":{"date-parts":[[2011,10,18]],"date-time":"2011-10-18T05:22:42Z","timestamp":1318915362000},"page":"495-506","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["<i>In Vitro<\/i>Effect of Malachite Green on Candida albicans Involves Multiple Pathways and Transcriptional Regulators<i>UPC2<\/i>and<i>STP2<\/i>"],"prefix":"10.1128","volume":"56","author":[{"given":"Sanjiveeni","family":"Dhamgaye","sequence":"first","affiliation":[{"name":"Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederic","family":"Devaux","sequence":"additional","affiliation":[{"name":"Laboratoire de Genetique Moleculaire, CNRS UMR8541, Ecole Normale Superieure, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raman","family":"Manoharlal","sequence":"additional","affiliation":[{"name":"Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Vandeputte","sequence":"additional","affiliation":[{"name":"Institut de Microbiologie, University of Lausanne and University Hospital Center, Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdul Haseeb","family":"Shah","sequence":"additional","affiliation":[{"name":"Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashutosh","family":"Singh","sequence":"additional","affiliation":[{"name":"Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne","family":"Blugeon","sequence":"additional","affiliation":[{"name":"Plate-Forme Transcriptome, IFR36, Institut de Biologie de l'ENS Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Sanglard","sequence":"additional","affiliation":[{"name":"Institut de Microbiologie, University of Lausanne and University Hospital Center, Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajendra","family":"Prasad","sequence":"additional","affiliation":[{"name":"Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000612"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00256-07"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07626.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth456"},{"key":"e_1_3_3_6_2","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/j.1365-2672.1995.tb03179.x","article-title":"Dyes as fungal inhibitors: effect on colony enumeration","volume":"79","author":"Bragulat MR","year":"1995","unstructured":"BragulatMR AbarcaML CastellaG CabanesFJ. 1995. Dyes as fungal inhibitors: effect on colony enumeration. J. Appl. Bacteriol. 79:578\u2013582.","journal-title":"J. Appl. Bacteriol"},{"key":"e_1_3_3_7_2","doi-asserted-by":"crossref","first-page":"44531","DOI":"10.1074\/jbc.M206525200","article-title":"Mitochondrial Hsp60, resistance to oxidative stress, and the labile iron pool are closely connected in Saccharomyces cerevisiae","volume":"277","author":"Cabiscol E","year":"2002","unstructured":"CabiscolE. 2002. Mitochondrial Hsp60, resistance to oxidative stress, and the labile iron pool are closely connected in Saccharomyces cerevisiae. J. Biol. Chem. 277:44531\u201344538.","journal-title":"J. Biol. Chem"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/BF00316351","article-title":"Toxicological studies on malachite green: a triphenylmethane dye","volume":"56","author":"Clemmensen S","year":"1984","unstructured":"ClemmensenS. 1984. Toxicological studies on malachite green: a triphenylmethane dye. Arch. Toxicol. 56:43\u201345.","journal-title":"Arch. Toxicol"},{"key":"e_1_3_3_9_2","unstructured":"Clinical and Laboratory Standards Institute (CLSI). 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard\u20143rd ed. CLSI document M27\u2013A3. Clinical and Laboratory Standards Institute Wayne PA."},{"key":"e_1_3_3_10_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0009-2797(99)00119-2","article-title":"Toxicity and metabolism of malachite green and leucomalachite green during short-term feeding to Fischer 344 rats and B6C3F1 mice","volume":"122","author":"Culp SJ","year":"1999","unstructured":"CulpSJ. 1999. Toxicity and metabolism of malachite green and leucomalachite green during short-term feeding to Fischer 344 rats and B6C3F1 mice. Chem. Biol. Interact. 122:153\u2013170.","journal-title":"Chem. Biol. Interact"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0027-5107(02)00152-5","article-title":"Mutagenicity and carcinogenicity in relation to DNA adduct formation in rats fed leucomalachite green","volume":"506","author":"Culp SJ","year":"2002","unstructured":"CulpSJ. 2002. Mutagenicity and carcinogenicity in relation to DNA adduct formation in rats fed leucomalachite green. Mutat. Res. 506\u2013507:55\u201363.","journal-title":"Mutat. Res"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/162.4.1573"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.20.12612"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-009-0453-4"},{"key":"e_1_3_3_15_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1006\/abio.1997.2126","article-title":"Fluorescence analysis of the labile iron pool of mammalian cells","volume":"248","author":"Epsztejn S","year":"1997","unstructured":"EpsztejnS KakhlonO GlicksteinH BreuerW CabantchikI. 1997. Fluorescence analysis of the labile iron pool of mammalian cells. Anal. Biochem. 248:31\u201340.","journal-title":"Anal. Biochem"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610197200"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/134.3.717"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.12.3065"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1439-0507.1999.00498.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.10.2987"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/yea.1044"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018684"},{"key":"e_1_3_3_23_2","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1002\/jcb.21960","article-title":"Establishment of a transgenic yeast screening system for estrogenicity and identification of the anti-estrogenic activity of malachite green","volume":"105","author":"Jiao B","year":"2008","unstructured":"JiaoB YeungEK ChanCB ChengCH. 2008. Establishment of a transgenic yeast screening system for estrogenicity and identification of the anti-estrogenic activity of malachite green. J. Cell. Biochem. 105:1399\u20131409.","journal-title":"J. Cell. Biochem"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.4.1046-1052.2002"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00091-07"},{"key":"e_1_3_3_26_2","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.bbagen.2008.03.008","article-title":"ROS accumulation and oxidative damage to cell structures in Saccharomyces cerevisiae wine strains during fermentation of high-sugar-containing medium","volume":"1780","author":"Landolfo S","year":"2008","unstructured":"LandolfoS PolitiH AngelozziD MannazzuI. 2008. ROS accumulation and oxidative damage to cell structures in Saccharomyces cerevisiae wine strains during fermentation of high-sugar-containing medium. Biochim. Biophys. Acta 1780:892\u2013898.","journal-title":"Biochim. Biophys. Acta"},{"key":"e_1_3_3_27_2","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1186\/1471-2105-7-467","article-title":"Goulphar: rapid access and expertise for standard two-color microarray normalization methods","volume":"7","author":"Lemoine S","year":"2006","unstructured":"LemoineS CombesF ServantN Le CromS. 2006. Goulphar: rapid access and expertise for standard two-color microarray normalization methods. BMC Bioinformatics 7:467.","journal-title":"BMC Bioinformatics"},{"key":"e_1_3_3_28_2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/jac\/dkn488","article-title":"Curcumin as a promising antifungal of clinical interest","volume":"63","author":"Martins CV","year":"2009","unstructured":"MartinsCV. 2009. Curcumin as a promising antifungal of clinical interest. J. Antimicrob. Chemother. 63:337\u2013339.","journal-title":"J. Antimicrob. Chemother"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12038-010-0014-6"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20071537"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-010-0147-0"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01393.x"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.12.3695-3705.2002"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1778-1787.2004"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.5.1528-1534.2001"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(03)00117-3"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(04)42005-1"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2004.06.021"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(06)11009-5"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.2144\/03342mt01"},{"key":"e_1_3_3_41_2","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1007\/s00253-003-1288-5","article-title":"Characterization of the metabolic shift of Saccharomyces bayanus var. uvarum by continuous aerobic culture","volume":"62","author":"Serra A","year":"2003","unstructured":"SerraA StrehaianoP TaillandierP. 2003. Characterization of the metabolic shift of Saccharomyces bayanus var. uvarum by continuous aerobic culture. Appl. Microbiol. Biotechnol. 62:564\u2013568.","journal-title":"Appl. Microbiol. Biotechnol"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20090151"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.6.1361-1375.2003"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10103-009-0706-z"},{"key":"e_1_3_3_45_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.aquatox.2003.09.008","article-title":"Toxicological effects of malachite green","volume":"66","author":"Srivastava S","year":"2004","unstructured":"SrivastavaS SinhaR RoyD. 2004. Toxicological effects of malachite green. Aquat. Toxicol. 66:319\u2013329.","journal-title":"Aquat. Toxicol"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00926-08"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.091062498"},{"key":"e_1_3_3_48_2","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ijantimicag.2008.10.033","article-title":"Effect of berberine on Staphylococcus epidermidis biofilm formation","volume":"34","author":"Wang X","year":"2009","unstructured":"WangX. 2009. Effect of berberine on Staphylococcus epidermidis biofilm formation. Int. J. Antimicrob. Agents 34:60\u201366.","journal-title":"Int. J. Antimicrob. Agents"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.6.1704-1713.2002"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.6.1868-1874.1999"},{"key":"e_1_3_3_51_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1158\/0008-5472.613.65.2","article-title":"Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia","volume":"65","author":"Xu RH","year":"2005","unstructured":"XuRH. 2005. Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res. 65:613\u2013621.","journal-title":"Cancer Res"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11046-009-9258-9"},{"key":"e_1_3_3_53_2","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1248\/yakushi.129.623","article-title":"Mechanism of action of tetrandrine, a natural inhibitor of Candida albicans drug efflux pumps","volume":"129","author":"Zhang H","year":"2009","unstructured":"ZhangH. 2009. Mechanism of action of tetrandrine, a natural inhibitor of Candida albicans drug efflux pumps. Yakugaku Zasshi 129:623\u2013630.","journal-title":"Yakugaku Zasshi"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00070-08"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00574-11","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00574-11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,10]],"date-time":"2023-06-10T14:34:21Z","timestamp":1686407661000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00574-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,1]]}},"alternative-id":["10.1128\/AAC.00574-11"],"URL":"https:\/\/doi.org\/10.1128\/aac.00574-11","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1]]},"assertion":[{"value":"2011-04-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-10-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-12-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}