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Several other\nspecies of\n                    <jats:italic>Candida<\/jats:italic>\n                    also displayed increased sensitivity to FLC\nbecause of iron restriction. Iron uptake mutations, namely,\u0394\n                    <jats:italic>ftr1<\/jats:italic>\n                    and \u0394\n                    <jats:italic>ftr2<\/jats:italic>\n                    , as well as the\ncopper transporter mutation \u0394\n                    <jats:italic>ccc2<\/jats:italic>\n                    , which affects\nhigh-affinity iron uptake in\n                    <jats:italic>Candida<\/jats:italic>\n                    , produced increased\nsensitivity to FLC compared to that of the wild type. The effect of\niron depletion on drug sensitivity appeared to be independent of the\nefflux pump proteins Cdr1p and Cdr2p. We found that iron deprivation\nled to lowering of membrane ergosterol by 15 to 30%. Subsequently,\nfluorescence polarization measurements also revealed that\niron-restricted\n                    <jats:italic>Candida<\/jats:italic>\n                    cells displayed a 29 to 40% increase\nin membrane fluidity, resulting in enhanced passive diffusion of the\ndrugs. Northern blot assays revealed that the\n                    <jats:italic>ERG11<\/jats:italic>\n                    gene was\nconsiderably down regulated in iron-deprived cells, which might account\nfor the lowered ergosterol content. Our results show a close\nrelationship between cellular iron and drug susceptibilities of\n                    <jats:italic>C. albicans<\/jats:italic>\n                    . Considering that multidrug resistance is\na manifestation of multifactorial phenomena, the influence of cellular\niron on the drug susceptibilities of\n                    <jats:italic>Candida<\/jats:italic>\n                    suggests iron as\nyet another novel determinant of multidrug\nresistance.\n                  <\/jats:p>","DOI":"10.1128\/aac.00653-06","type":"journal-article","created":{"date-parts":[[2006,10,25]],"date-time":"2006-10-25T16:58:50Z","timestamp":1161795530000},"page":"3597-3606","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":140,"title":["Unexpected Link between Iron and Drug Resistance of\n                    <i>Candida<\/i>\n                    spp.: Iron Depletion Enhances Membrane Fluidity and Drug Diffusion, Leading to Drug-SusceptibleCells"],"prefix":"10.1128","volume":"50","author":[{"given":"Tulika","family":"Prasad","sequence":"first","affiliation":[{"name":"Membrane\rBiology Laboratory, School of Life\rSciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Chandra","sequence":"additional","affiliation":[{"name":"Special Center for Molecular\rMedicine, Jawaharlal Nehru University, New\rDelhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinmay K.","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Special Center for Molecular\rMedicine, Jawaharlal Nehru University, New\rDelhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra","family":"Prasad","sequence":"additional","affiliation":[{"name":"Membrane\rBiology Laboratory, School of Life\rSciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780500138971"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90346-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1996.tb02485.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.1.401"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.46386-0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026043387269"},{"key":"e_1_3_2_8_2","first-page":"3387","volume":"62","year":"2002","unstructured":"Comerford, K. 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