{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:48:21Z","timestamp":1790628501970,"version":"4.1.0"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T00:00:00Z","timestamp":1535500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0203079","type":"journal-article","created":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T15:13:05Z","timestamp":1535555585000},"page":"e0203079","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":80,"title":["Fungicidal action of geraniol against Candida albicans is potentiated by abrogated CaCdr1p drug efflux and fluconazole synergism"],"prefix":"10.1371","volume":"13","author":[{"given":"Shweta","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeeshan","family":"Fatima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1744-6554","authenticated-orcid":true,"given":"Kamal","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-1870","authenticated-orcid":true,"given":"Saif","family":"Hameed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2018,8,29]]},"reference":[{"key":"ref1","first-page":"211","article-title":"Predisposing factors endorsing Candida infections","volume":"23","author":"S Singh","year":"2015","journal-title":"Infez Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"13363","DOI":"10.1128\/CMR.00029-06","article-title":"Epidemiology of invasive candidiasis: a persistent public health problem","volume":"20","author":"MA Pfaller","year":"2007","journal-title":"Clin Microbiol Rev"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/jac\/dki218","article-title":"Changing patterns and trends in systemic function infections","volume":"56","author":"MD Richardson","year":"2005","journal-title":"J Antimicrob Chemother"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1128\/AAC.46.6.1704-1713.2002","article-title":"Resistance mechanisms in clinical isolates of <italic>Candida albicans<\/italic>","volume":"46","author":"TC White","year":"2002","journal-title":"Antimicrob Agents Chemother"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2147\/IDR.S118892","article-title":"Fluconazole resistance in Candida species: a current perspective","volume":"10","author":"EL Berkow","year":"2017","journal-title":"Infect Drug Resist"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"541340","DOI":"10.1155\/2014\/541340","article-title":"Multidrug resistance: an emerging crisis","volume":"2014","author":"J Tanwar","year":"2014","journal-title":"Interdiscip Perspect Infect Dis"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"240209","DOI":"10.1155\/2013\/240209","article-title":"Novel regulatory mechanisms of pathogenicity and virulence to combat MDR in <italic>Candida albicans<\/italic>","volume":"2013","author":"S Hameed","year":"2013","journal-title":"Int J Microbiol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0065-2911(02)46004-3","article-title":"Smriti. Drug resistance in yeasts as an emerging scenario","volume":"46","author":"R Prasad","year":"2002","journal-title":"Adv Microb Physiol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"69","DOI":"10.2174\/187152606784112164","article-title":"Efflux pumps in drug resistance of Candida","volume":"6","author":"R Prasad","year":"2006","journal-title":"Infect Disord Drug Targets"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nrc706","article-title":"Multidrug resistance in cancer: role of ATP-dependent transporters","volume":"2","author":"MM Gottesman","year":"2002","journal-title":"Nat Rev Cancer"},{"key":"ref11","first-page":"1","article-title":"Frontiers in Anti-Infective Drug Discovery","volume":"7","author":"S Singh","year":"2017"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1128\/AAC.01497-08","article-title":"Curcumin modulates efflux mediated by yeast ABC multidrug transporters and is synergistic with antifungals","volume":"53","author":"M Sharma","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/j.1365-2672.2007.03617.x","article-title":"Plagiochin E, a botanic-derived phenolic compound, reverses fungal resistance to fluconazole relating to the efflux pump","volume":"104","author":"XL Guo","year":"2008","journal-title":"J Appl Microbiol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1055\/s-0042-106169","article-title":"Overcoming multidrug resistance in <italic>Candida albicans<\/italic>: macrocyclic diterpenes from Euphorbia species as potent inhibitors of drug efflux pumps","volume":"82","author":"S Nim","year":"2016","journal-title":"Planta Med"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jep.2013.03.069","article-title":"Tchoumbougnang F Antibacterial, cytotoxic activities and chemical composition of fruits of two Cameroonian Zanthoxylum species","volume":"148","author":"LN Misra","year":"2013","journal-title":"J Ethnopharmacol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s00203-016-1205-9","article-title":"Hameed. Insights into the mode of action of anticandidal herbal monoterpenoid geraniol reveal disruption of multiple MDR mechanisms and virulence attributes in <italic>Candida albicans<\/italic>","volume":"198","author":"S Singh","year":"2016","journal-title":"Arch Microbiol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.bbrc.2005.03.009","article-title":"A new function of isonitrile as an inhibitor of the Pdr5p multidrug ABC transporter in <italic>Saccharomyces cerevisiae<\/italic>","volume":"330","author":"S Yamamoto","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3109\/13693786.2011.578156","article-title":"Curcumin acts synergistically with fluconazole to sensitize a clinical isolate of <italic>Candida albicans<\/italic> showing a MDR phenotype","volume":"50","author":"AS Garcia-Gomes","year":"2012","journal-title":"Med Mycol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1128\/EC.2.6.1361-1375.2003","article-title":"Functional characterization of <italic>Candida albicans<\/italic> ABC transporter Cdr1p","volume":"2","author":"S Shukla","year":"2003","journal-title":"Eukaryot Cell"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1741-7007-5-17","article-title":"Ab initio modeling of small proteins by iterative TASSER simulations","volume":"5","author":"S Wu","year":"2007","journal-title":"BMC Biol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-1-4939-7231-9_4","article-title":"Protein Structure Modeling with MODELLER","volume":"1654","author":"B Webb","year":"2017","journal-title":"Methods Mol Biol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.bbrc.2017.11.064","article-title":"Monoterpenoid perillyl alcohol impairs metabolic flexibility of <italic>Candida albicans<\/italic> by inhibiting glyoxylate cycle","volume":"495","author":"MA Ansari","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"488e","DOI":"10.2174\/1570180814666161214114322","article-title":"Pharmacokinetic evaluation of Callistemon viminalis derived natural compounds as targeted inhibitors against d-opioid receptor and farnesyl transferase","volume":"14","author":"K Ahmad","year":"2017","journal-title":"Lett. Drug Des. Discov"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"4834","DOI":"10.1128\/AAC.00344-11","article-title":"The quorum-sensing molecule farnesol is a modulator of drug efflux mediated by ABC multidrug transporters and synergizes with drugs in <italic>Candida albicans<\/italic>","volume":"55","author":"M Sharma","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"key":"ref25","first-page":"1","article-title":"Flexible ligand docking with Glide","author":"MP Repasky","year":"2007","journal-title":"Current Protocols in Bioinformatics"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1002\/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B","article-title":"Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function","volume":"14","author":"GM Morris","year":"1998","journal-title":"J. Comput. Chem"},{"issue":"9","key":"ref27","doi-asserted-by":"crossref","first-page":"e0162465","DOI":"10.1371\/journal.pone.0162465","article-title":"Anticandidal effect and mechanisms of monoterpenoid, perillyl alcohol against Candida albicans","author":"MA Ansari","year":"2016","journal-title":"PLoS One"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ijantimicag.2017.01.044","article-title":"Blocking and dislocation of Candida albicans Cdr1p transporter by styrylquinolines","volume":"50","author":"J Szczepaniak","year":"2017","journal-title":"Int J Antimicrob Agents"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0165-022X(03)00032-0","article-title":"Rhodamine B as a mitochondrial probe for measurement and monitoring of mitochondrial membrane potential in drug-sensitive and -resistant cells","volume":"57","author":"P Reungpatthanaphong","year":"2003","journal-title":"J Biochem Biophys Methods"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1371\/journal.ppat.0030018","article-title":"Antifungal chemical compounds identified using a C. elegans pathogenicity assay","volume":"3","author":"J Breger","year":"2007","journal-title":"PLoS Pathog"},{"key":"ref31","first-page":"14","article-title":"Reference method for broth dilution antifungal susceptibility testing of yeasts, Approved standard M27-A3","volume":"28","year":"2008"},{"issue":"4","key":"ref32","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1590\/0037-8682-0190-2016","article-title":"Citronellal-induced disruption of membrane homeostasis in <italic>Candida albicans<\/italic> and attenuation of its virulence attributes","volume":"49","author":"S Singh","year":"2016","journal-title":"Rev Soc Bras Med Trop"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.ijantimicag.2017.03.015","article-title":"Strong synergism of dexamethasone in combination with fluconazole against resistant <italic>Candida albicans<\/italic> mediated by inhibiting drug efflux and reducing virulence","volume":"50","author":"W Sun","year":"2017","journal-title":"Int J Antimicrob Agents"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"444","DOI":"10.3109\/13693786.2010.539629","article-title":"Effect of garlic-derived allyl sulphides on morphogenesis and hydrolytic enzyme secretion in <italic>Candida albicans<\/italic>","volume":"49","author":"S Yousuf","year":"2011","journal-title":"Med Mycol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"6179","DOI":"10.1128\/AAC.03046-15","article-title":"The Synergistic Effect of Azoles and Fluoxetine against Resistant <italic>Candida albicans<\/italic> Strains Is Attributed to Attenuating Fungal Virulence","volume":"60","author":"W Gu","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.micpath.2016.07.004","article-title":"Mechanistic insights into the mode of action of anticandidal sesamol","volume":"98","author":"MA Ansari","year":"2016","journal-title":"Microb Pathog"},{"issue":"11","key":"ref37","doi-asserted-by":"crossref","first-page":"e79671","DOI":"10.1371\/journal.pone.0079671","article-title":"Effect of tetrandrine against <italic>Candida albicans<\/italic> biofilms","volume":"8","author":"LX Zhao","year":"2013","journal-title":"PLoS One"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"55042","DOI":"10.1074\/jbc.M408881200","article-title":"Dissection of antibacterial and toxic activity of melittin: a leucine zipper motif plays a crucial role in determining its hemolytic activity but not antibacterial activity","volume":"279","author":"N Asthana","year":"2004","journal-title":"J Biol Chem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"12612","DOI":"10.1074\/jbc.273.20.12612","article-title":"ATPase and multidrug transport activities of the overexpressed yeast ABC protein Yor1p","volume":"273","author":"A Decottignies","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1128\/EC.2.6.1361-1375.2003","article-title":"Functional characterization of <italic>Candida albicans<\/italic> ABC transporter Cdr1p","volume":"2","author":"S Shukla","year":"2003","journal-title":"Eukaryot. Cell"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1128\/EC.00315-06","article-title":"Structure and function analysis of CaMdr1p, a major facilitator superfamily antifungal efflux transporter protein of <italic>Candida albicans<\/italic>: identification of amino acid residues critical for drug\/H_ transport","volume":"6","author":"R Pasrija","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1093\/emboj\/21.4.546","article-title":"Calcineurin is essential for survival during membrane stress in <italic>Candida albicans<\/italic>","volume":"21","author":"MC Cruz","year":"2002","journal-title":"EMBO. J"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nprot.2010.5","article-title":"I-TASSER: a unified platform for automated protein structure and function prediction","volume":"5","author":"A Roy","year":"2010","journal-title":"Nat Protoc"},{"issue":"W1","key":"ref44","doi-asserted-by":"crossref","first-page":"W174","DOI":"10.1093\/nar\/gkv342","article-title":"I-TASSER server: new development for protein structure and function predictions","volume":"43","author":"J Yang","year":"2015","journal-title":"Nucleic acids research"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1002\/prot.20264","article-title":"Scoring function for automated assessment of protein structure template quality","volume":"57","author":"Y Zhang","year":"2004","journal-title":"Proteins"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1128\/AAC.42.12.3065","article-title":"Multiple molecular mechanisms contribute to a stepwise development of fluconazole resistance in clinical <italic>Candida albicans<\/italic> strains","volume":"42","author":"R Franz","year":"1998","journal-title":"Antimicrob Agents Chemother"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1046\/j.1439-0507.1999.00498.x","article-title":"Molecular aspects of fluconazole resistance development in <italic>Candida albicans<\/italic>","volume":"42","author":"R Franz","year":"1999","journal-title":"Mycoses"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"783","DOI":"10.3389\/fmicb.2015.00783","article-title":"Chemosensitization of multidrug resistant Candida albicans by the oxathiolone fused chalcone derivatives","volume":"6","author":"I \u0141a\u0327cka","year":"2015","journal-title":"Front Microbiol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/1567-1364.12148","article-title":"The putative transcription factor CaRtg3 is involved in tolerance to cations and antifungal drugs as well as serum-induced filamentation in <italic>Candida albicans<\/italic>","volume":"14","author":"H Yan","year":"2014","journal-title":"FEMS. Yeast. Res"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"398","DOI":"10.11604\/pamj.2014.19.398.4960","article-title":"A surveillance of nosocomial candida infections: epidemiology and influences on mortalty in intensive care units","volume":"19","author":"Z Karacaer","year":"2014","journal-title":"Pan Afr Med J"},{"key":"ref51","first-page":"3242","article-title":"Modulators of the Efflux Pump Cdr1p of <italic>Candida albicans<\/italic>: Mechanisms of Action and Chemical Features","volume":"24","author":"VK Tran-Nguyen","year":"2017","journal-title":"Curr Med Chem"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3389\/fphar.2014.00202","article-title":"Efflux pump proteins in antifungal resistance","volume":"5","author":"R Prasad","year":"2014","journal-title":"Front Pharmacol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.synbio.2016.10.001","article-title":"Beauvericin counteracted multi-drug resistant Candida albicans by blocking ABC transporters","author":"Y Tong","year":"2016","journal-title":"Synth Syst Biotechnol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"33687","DOI":"10.1038\/srep33687","article-title":"Quinone derivatives isolated from the endolichenic fungus Phialocephala fortinii are Mdr1 modulators that combat azole resistance in Candida albicans","volume":"6","author":"F Xie","year":"2016","journal-title":"Sci Rep"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1016\/j.bbamem.2017.05.011","article-title":"Multidrug ABC transporter Cdr1 of <italic>Candida albicans<\/italic> harbors specific and overlapping binding sites for human steroid hormones transport","volume":"1859","author":"P Baghel","year":"2017","journal-title":"Biochim Biophys Acta"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1128\/AAC.00861-07","article-title":"Multidrug transporters CaCdr1p and CaMdr1p of <italic>Candida albicans<\/italic> display different lipid specificities: both ergosterol and sphingolipids are essential for targeting of CaCdr1p to membrane rafts","volume":"52","author":"R Pasrija","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1128\/EC.00066-09","article-title":"Goa1p of <italic>Candida albicans<\/italic> localizes to the mitochondria during stress and is required for mitochondrial function and virulence","volume":"8","author":"A Bambach","year":"2009","journal-title":"Eukaryot Cell"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1128\/EC.05292-11","article-title":"Mitochondrial sorting and assembly machinery subunit Sam37 in <italic>Candida albicans<\/italic>: insight into the roles of mitochondria in fitness, cell wall integrity, and virulence","volume":"11","author":"Y Qu","year":"2012","journal-title":"Eukaryot Cell"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"5580","DOI":"10.1128\/AAC.00889-13","article-title":"Mitochondria influence CDR1 efflux pump activity, Hog1-mediated oxidative stress pathway, iron homeostasis, and ergosterol levels in <italic>Candida albicans<\/italic>","volume":"57","author":"E Thomas","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/1471-2180-10-114","article-title":"Real-time PCR expression profiling of genes encoding potential virulence factors in <italic>Candida albicans<\/italic> biofilms: identification of model-dependent and -independent gene expression","volume":"10","author":"H Nailis","year":"2010","journal-title":"BMC Microbiol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0203079","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T05:20:09Z","timestamp":1589001609000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0203079"}},"subtitle":[],"editor":[{"given":"Joy","family":"Sturtevant","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,8,29]]},"references-count":60,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2018,8,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0203079","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,29]]}}}