{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T01:19:58Z","timestamp":1773364798590,"version":"3.50.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["OMI-Fellowship\/5\/2019-ECD-1"],"award-info":[{"award-number":["OMI-Fellowship\/5\/2019-ECD-1"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biometals"],"published-print":{"date-parts":[[2021,4]]},"DOI":"10.1007\/s10534-020-00282-w","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T11:04:23Z","timestamp":1609758263000},"page":"329-339","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Insights into the modulatory effect of magnesium on efflux mechanisms of Candida albicans reveal inhibition of ATP binding cassette multidrug transporters and dysfunctional mitochondria"],"prefix":"10.1007","volume":"34","author":[{"given":"Sandeep","family":"Hans","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeeshan","family":"Fatima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saif","family":"Hameed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"issue":"10","key":"282_CR1","doi-asserted-by":"publisher","first-page":"3332","DOI":"10.1128\/JCM.37.10.3332-3337.1999","volume":"37","author":"BA Arthington-Skaggs","year":"1999","unstructured":"Arthington-Skaggs BA, Jradi H, Desai T, Morrison CJ (1999) Quantitation of ergosterol content: novel method for determination of fluconazole susceptibility of Candida albicans. J Clin Microbiol 37(10):3332\u20133337","journal-title":"J Clin Microbiol"},{"key":"282_CR2","doi-asserted-by":"publisher","first-page":"237","DOI":"10.2147\/IDR.S118892","volume":"10","author":"EL Berkow","year":"2017","unstructured":"Berkow EL, Lockhart SR (2017) Fluconazole resistance in Candida species: a current perspective. Infect Drug Resist 10:237\u2013245","journal-title":"Infect Drug Resist"},{"issue":"8","key":"282_CR3","first-page":"1012","volume":"56","author":"RSN Brilhante","year":"2018","unstructured":"Brilhante RSN, de Oliveira JS, de Jesus Evangelista AJ, Pereira VS, Alencar LP, Castelo-Branco DSCM et al (2018) In vitro effects of promethazine on cell morphology and structure and mitochondrial activity of azole-resistant Candida tropicalis. Med Mycol 56(8):1012\u20131022","journal-title":"Med Mycol"},{"issue":"2","key":"282_CR4","doi-asserted-by":"publisher","first-page":"345","DOI":"10.3390\/molecules25020345","volume":"25","author":"W Cieslik","year":"2020","unstructured":"Cieslik W, Szczepaniak J, Krasowska A, Musio R (2020) Antifungal Styryloquinolines as Candida albicans efflux pump inhibitors: Styryloquinolines are ABC transporter inhibitors. Molecules 25(2):345","journal-title":"Molecules"},{"key":"282_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1152\/physrev.00012.2014","volume":"95","author":"JH de Baaij","year":"2015","unstructured":"de Baaij JH, Hoenderop JG, Bindels RJ (2015) Magnesium in man: implications for health and disease. Physiol Rev 95:1\u201346","journal-title":"Physiol Rev"},{"key":"282_CR6","doi-asserted-by":"publisher","first-page":"3065","DOI":"10.1128\/AAC.42.12.3065","volume":"42","author":"R Franz","year":"1998","unstructured":"Franz R, Kelly SL, Lamb DC, Kelly DE, Ruhnke M, Morschha\u00c8user J (1998) Multiple molecular mechanisms contribute to a stepwise development of fluconazole resistance in clinical Candida albicans strains. Antimicrob Agents Chemother 42:3065\u20133072","journal-title":"Antimicrob Agents Chemother"},{"key":"282_CR7","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1046\/j.1439-0507.1999.00498.x","volume":"42","author":"R Franz","year":"1999","unstructured":"Franz R, Ruhnke M, Morschha\u00c8user J (1999) Molecular aspects of fluconazole resistance development in Candida albicans. Mycoses 42:453\u2013458","journal-title":"Mycoses"},{"key":"282_CR8","doi-asserted-by":"publisher","first-page":"16216","DOI":"10.1074\/jbc.M101504200","volume":"276","author":"A Graschopf","year":"2001","unstructured":"Graschopf A, Stadler JA, Hoellerer MK, Eder S, Sieghardt M, Kohlwein SD et al (2001) The yeast plasma membrane protein Alr1 controls Mg2+ homeostasis and is subject to Mg2+-dependent control of its synthesis and degradation. J Biol Chem 276:16216\u201316222","journal-title":"J Biol Chem"},{"key":"282_CR9","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jgar.2019.01.011","volume":"17","author":"S Hans","year":"2019","unstructured":"Hans S, Fatima Z, Hameed S (2019a) Magnesium deprivation affects cellular circuitry involved in drug resistance and virulence in Candida albicans. J Glob Antimicrob Resist 17:263\u2013275","journal-title":"J Glob Antimicrob Resist"},{"key":"282_CR10","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.mycmed.2019.07.003","volume":"29","author":"S Hans","year":"2019","unstructured":"Hans S, Fatima Z, Hameed S (2019b) Retrograde signaling disruption influences ABC superfamily transporter, ergosterol and chitin levels along with biofilm formation in Candida albicans. J Mycol Med 29:210\u2013218","journal-title":"J Mycol Med"},{"key":"282_CR11","doi-asserted-by":"publisher","first-page":"3851","DOI":"10.1128\/AAC.00463-08","volume":"52","author":"AR Holmes","year":"2008","unstructured":"Holmes AR, Lin YH, Niimi K, Lamping E, Keniya M, Niimi M et al (2008) ABC transporter Cdr1p contributes more than Cdr2p does to fluconazole efflux in fluconazole-resistant Candida albicans clinical isolates. Antimicrob Agents Chemother 52:3851\u20133862","journal-title":"Antimicrob Agents Chemother"},{"key":"282_CR12","doi-asserted-by":"publisher","first-page":"e00334-18","DOI":"10.1128\/mSphere.00334-18","volume":"3","author":"R Kean","year":"2018","unstructured":"Kean R, Delaney C, Sherry L, Borman A, Johnson EM, Richardson MD et al (2018) Transcriptome assembly and profiling of Candida auris reveals novel insights into biofilm-mediated resistance. mSphere 3:e00334-18","journal-title":"mSphere"},{"key":"282_CR13","first-page":"783","volume":"6","author":"I L\u00e8a\u00cbcka","year":"2015","unstructured":"L\u00e8a\u00cbcka I, Konieczny MT, Bu\u00f8akowska A, Kodedova\u00c2 M, Gas\u00cfkova\u00c2 D, Maurya IK (2015) Chemosensitization of multidrug resistant Candida albicans by the oxathiolone fused chalcone derivatives. Front Microbiol 6:783","journal-title":"Front Microbiol"},{"issue":"11","key":"282_CR14","doi-asserted-by":"publisher","first-page":"e0243066","DOI":"10.1371\/journal.pone.0243066","volume":"15","author":"Y Li","year":"2020","unstructured":"Li Y, Shan M, Zhu Y, Yao H, Li H, Gu B, Zhu Z (2020) Kalopanaxsaponin A induces reactive oxygen species mediated mitochondrial dysfunction and cell membrane destruction in Candida albicans. PLoS ONE 15(11):e0243066","journal-title":"PLoS ONE"},{"key":"282_CR15","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1074\/jbc.273.3.1727","volume":"273","author":"CW MacDiarmid","year":"1998","unstructured":"MacDiarmid CW, Gardner RC (1998) Overexpression of the Saccharomyces cerevisiae magnesium transport system confers resistance to aluminum ion. J Biol Chem 273:1727\u20131732","journal-title":"J Biol Chem"},{"key":"282_CR16","doi-asserted-by":"publisher","first-page":"3366","DOI":"10.1128\/AAC.45.12.3366-3374.2001","volume":"45","author":"K Nakamura","year":"2001","unstructured":"Nakamura K, Niimi M, Niimi K, Holmes AR, Yates JE, Decottignies A et al (2001) Functional expression of Candida albicans drug efflux pump Cdr1p in a Saccharomyces cerevisiae strain deficient in membrane transporters. Antimicrob Agents Chemother 45:3366\u20133374","journal-title":"Antimicrob Agents Chemother"},{"key":"282_CR17","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1128\/AAC.48.4.1256-1271.2004","volume":"48","author":"K Niimi","year":"2004","unstructured":"Niimi K, Harding DRK, Parshot R, King A, Lun DJ, Decottignies A et al (2004) Chemosensitization of fluconazole resistance in Saccharomyces cerevisiae and pathogenic fungi by a d-octapeptide derivative. Antimicrob Agents Chemother 48:1256\u20131271","journal-title":"Antimicrob Agents Chemother"},{"key":"282_CR18","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1128\/EC.00315-06","volume":"6","author":"R Pasrija","year":"2007","unstructured":"Pasrija R, Banerjee D, Prasad R (2007) Structure and function analysis of CaMdr1p, a major facilitator superfamily antifungal efflux transporter protein of Candida albicans: identification of amino acid residues critical for drug\/H_ transport. Eukaryot Cell 6:443\u2013453","journal-title":"Eukaryot Cell"},{"key":"282_CR19","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1128\/AAC.00861-07","volume":"52","author":"R Pasrija","year":"2008","unstructured":"Pasrija R, Panwar SL, Prasad R (2008) Multidrug transporters CaCdr1p and CaMdr1p of Candida albicans display different lipid specificities: both ergosterol and sphingolipids are essential for targeting of CaCdr1p to membrane rafts. Antimicrob Agents Chemother 52:694\u2013704","journal-title":"Antimicrob Agents Chemother"},{"key":"282_CR20","doi-asserted-by":"publisher","first-page":"13363","DOI":"10.1128\/CMR.00029-06","volume":"20","author":"MA Pfaller","year":"2007","unstructured":"Pfaller MA, Diekema DJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20:13363","journal-title":"Clin Microbiol Rev"},{"key":"282_CR21","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1128\/EC.05292-11","volume":"11","author":"Y Qu","year":"2012","unstructured":"Qu Y, Jelicic B, Pettolino F, Perry A, Lo TL, Hewitt VL et al (2012) Mitochondrial sorting and assembly machinery subunit Sam37 in Candida albicans: insight into the roles of mitochondria in fitness, cell wall integrity, and virulence. Eukaryot Cell 11:532\u2013544","journal-title":"Eukaryot Cell"},{"key":"282_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0165-022X(03)00032-0","volume":"57","author":"P Reungpatthanaphong","year":"2003","unstructured":"Reungpatthanaphong P, Dechsupa S, Meesungnoen J, Loetchutinat C, Mankhetkorn S (2003) Rhodamine B as a mitochondrial probe for measurement and monitoring of mitochondrial membrane potential in drug sensitive and -resistant cells. J Biochem Biophys Methods 57:1\u201316","journal-title":"J Biochem Biophys Methods"},{"issue":"3","key":"282_CR23","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1093\/mmy\/myz054","volume":"58","author":"V Saibabu","year":"2020","unstructured":"Saibabu V, Fatima Z, Ahmad K, Khan LA, Hameed S (2020) Octyl gallate triggers dysfunctional mitochondria leading to ROS driven membrane damage and metabolic inflexibility along with attenuated virulence in Candida albicans. Med Mycol 58(3):380\u2013392","journal-title":"Med Mycol"},{"key":"282_CR24","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1099\/00221287-143-2-405","volume":"143","author":"D Sanglard","year":"1997","unstructured":"Sanglard D, Ischer F, Monod M, Bille J (1997) Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene. Microbiology 143:405\u2013416","journal-title":"Microbiology"},{"key":"282_CR25","doi-asserted-by":"publisher","first-page":"4834","DOI":"10.1128\/AAC.00344-11","volume":"55","author":"M Sharma","year":"2011","unstructured":"Sharma M, Prasad R (2011) The quorum-sensing molecule farnesol is a modulator of drug efflux mediated by ABC multidrug transporters and synergizes with drugs in Candida albicans. Antimicrob Agents Chemother 55:4834\u20134843","journal-title":"Antimicrob Agents Chemother"},{"key":"282_CR26","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1128\/EC.2.6.1361-1375.2003","volume":"2","author":"S Shukla","year":"2003","unstructured":"Shukla S, Saini P, Smriti Jha S, Ambudkar SV, Prasad R (2003) Functional characterization of Candida albicans ABC transporter Cdr1p. Eukaryot Cell 2:1361\u20131375","journal-title":"Eukaryot Cell"},{"key":"282_CR27","doi-asserted-by":"publisher","first-page":"e0203079","DOI":"10.1371\/journal.pone.0203079","volume":"13","author":"S Singh","year":"2018","unstructured":"Singh S, Fatima Z, Ahmad K, Hameed S (2018) Fungicidal action of geraniol against Candida albicans is potentiated by abrogated CaCdr1p drug efflux and fluconazole synergism. PLoS ONE 13:e0203079","journal-title":"PLoS ONE"},{"key":"282_CR28","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1002\/yea.818","volume":"19","author":"KS Smriti","year":"2002","unstructured":"Smriti KS, Dixit BL, Gupta CM, Milewski S, Prasad R (2002) ABC transporters Cdr1p, Cdr2p and Cdr3p of a human pathogen Candida albicans are general phospholipid translocators. Yeast 19:303\u2013318","journal-title":"Yeast"},{"key":"282_CR29","first-page":"4237","volume":"20","author":"C Spampinato","year":"2013","unstructured":"Spampinato C, Leonardi D (2013) Candida infections, causes, targets, and resistance mechanisms: traditional and alternative antifungal agents. Biomed Res Int 20:4237","journal-title":"Biomed Res Int"},{"issue":"10","key":"282_CR30","doi-asserted-by":"publisher","first-page":"378","DOI":"10.3390\/microorganisms7100378","volume":"7","author":"J Suchodolski","year":"2019","unstructured":"Suchodolski J, Muraszko J, Bernat P, Krasowska A (2019) A crucial role for ergosterol in plasma membrane composition, localisation, and activity of Cdr1p and H+-ATPase in Candida albicans. Microorganisms 7(10):378","journal-title":"Microorganisms"},{"key":"282_CR31","doi-asserted-by":"publisher","first-page":"5580","DOI":"10.1128\/AAC.00889-13","volume":"57","author":"E Thomas","year":"2013","unstructured":"Thomas E, Roman E, Claypool S, Manzoor N, Pla J, Panwar SL (2013) Mitochondria influence CDR1 efflux pump activity, Hog1-mediated oxidative stress pathway, iron homeostasis, and ergosterol levels in Candida albicans. Antimicrob Agents Chemother 57:5580\u20135599","journal-title":"Antimicrob Agents Chemother"},{"key":"282_CR32","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1128\/AAC.46.6.1704-1713.2002","volume":"46","author":"TC White","year":"2002","unstructured":"White TC, Holleman S, Dy F, Mirels LF, Stevens DA (2002) Resistance mechanisms in clinical isolates of Candida albicans. Antimicrob Agents Chemother 46:1704\u20131713","journal-title":"Antimicrob Agents Chemother"},{"key":"282_CR33","doi-asserted-by":"publisher","first-page":"e92","DOI":"10.1371\/journal.ppat.0030092","volume":"3","author":"D Xu","year":"2007","unstructured":"Xu D, Jiang B, Ketela T, Lemieux S, Veillette K, Martel N et al (2007) Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans. PLoS Pathog 3:e92","journal-title":"PLoS Pathog"},{"key":"282_CR34","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1016\/j.ygeno.2018.08.001","volume":"111","author":"H Xu","year":"2019","unstructured":"Xu H, Whiteway M, Jiang L (2019) The tricarboxylic acid cycle, cell wall integrity pathway, cytokinesis and intracellular pH homeostasis are involved in the sensitivity of Candida albicans cells to high levels of extracellular calcium. Genomics 111:1226\u20131230","journal-title":"Genomics"},{"key":"282_CR35","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.bbrc.2005.03.009","volume":"330","author":"S Yamamoto","year":"2005","unstructured":"Yamamoto S, Hiraga K, Abiko A, Hamanaka N, Oda K (2005) A new function of isonitrile as an inhibitor of the Pdr5p multidrug ABC transporter in Saccharomyces cerevisiae. Biochem Biophys Res Commun 330:622\u2013628","journal-title":"Biochem Biophys Res Commun"},{"key":"282_CR36","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1248\/yakushi.129.623","volume":"129","author":"H Zhang","year":"2009","unstructured":"Zhang H, Gao A, Li F, Zhang G, Ho HI, Liao W (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":"282_CR37","doi-asserted-by":"publisher","first-page":"e1000939","DOI":"10.1371\/journal.ppat.1000939","volume":"6","author":"YQ Zhang","year":"2010","unstructured":"Zhang YQ, Gamarra S, Garcia-Effron G, Park S, Perlin DS, Rao R (2010) Requirement for ergosterol in V-ATPase function underlies antifungal activity of azole drugs. PLoS Pathog 6:e1000939","journal-title":"PLoS Pathog"},{"issue":"1","key":"282_CR38","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/s41598-017-18717-9","volume":"8","author":"S Zheng","year":"2018","unstructured":"Zheng S, Chang W, Zhang M, Shi H, Lou H (2018) Chiloscyphenol A derived from Chinese liverworts exerts fungicidal action by eliciting both mitochondrial dysfunction and plasma membrane destruction. Sci Rep 8(1):326","journal-title":"Sci Rep"}],"container-title":["BioMetals"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10534-020-00282-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10534-020-00282-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10534-020-00282-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T10:05:25Z","timestamp":1615197925000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10534-020-00282-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,4]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["282"],"URL":"https:\/\/doi.org\/10.1007\/s10534-020-00282-w","relation":{},"ISSN":["0966-0844","1572-8773"],"issn-type":[{"value":"0966-0844","type":"print"},{"value":"1572-8773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,4]]},"assertion":[{"value":"7 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}