{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:39:45Z","timestamp":1788845985863,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T00:00:00Z","timestamp":1620950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2016\/23\/B\/NZ1\/01928"],"award-info":[{"award-number":["2016\/23\/B\/NZ1\/01928"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Candida albicans is an opportunistic pathogen that induces vulvovaginal candidiasis (VVC), among other diseases. In the vaginal environment, the source of carbon for C. albicans can be either lactic acid or its dissociated form, lactate. It has been shown that lactate, similar to the popular antifungal drug fluconazole (FLC), reduces the expression of the ERG11 gene and hence the amount of ergosterol in the plasma membrane. The Cdr1 transporter that effluxes xenobiotics from C. albicans cells, including FLC, is delocalized from the plasma membrane to a vacuole under the influence of lactate. Despite the overexpression of the CDR1 gene and the increased activity of Cdr1p, C. albicans is fourfold more sensitive to FLC in the presence of lactate than when glucose is the source of carbon. We propose synergistic effects of lactate and FLC in that they block Cdr1 activity by delocalization due to changes in the ergosterol content of the plasma membrane.<\/jats:p>","DOI":"10.3390\/ijms22105219","type":"journal-article","created":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T10:54:22Z","timestamp":1620989662000},"page":"5219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Lactate Like Fluconazole Reduces Ergosterol Content in the Plasma Membrane and Synergistically Kills Candida albicans"],"prefix":"10.3390","volume":"22","author":[{"given":"Jakub","family":"Suchodolski","sequence":"first","affiliation":[{"name":"Department of Biotransformation, Faculty of Biotechnology, University of Wroc\u0142aw, 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7232-0298","authenticated-orcid":false,"given":"Jakub","family":"Muraszko","sequence":"additional","affiliation":[{"name":"Department of Biotransformation, Faculty of Biotechnology, University of Wroc\u0142aw, 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-1555","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Bernat","sequence":"additional","affiliation":[{"name":"Department of Industrial Microbiology and Biotechnology, Faculty of Biology and Environmental Protection, University of \u0141\u00f3d\u017a, 90-237 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1925-193X","authenticated-orcid":false,"given":"Anna","family":"Krasowska","sequence":"additional","affiliation":[{"name":"Department of Biotransformation, Faculty of Biotechnology, University of Wroc\u0142aw, 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1016\/S0140-6736(07)60917-9","article-title":"Vulvovaginal candidosis","volume":"369","author":"Sobel","year":"2007","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1111\/1567-1364.12145","article-title":"Genome structure and dynamics of the yeast pathogen Candida glabrata","volume":"14","author":"Ahmad","year":"2014","journal-title":"FEMS Yeast Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1111\/cmi.12091","article-title":"Two unlike cousins: Candida albicans and C. glabrata infection strategies","volume":"15","author":"Brunke","year":"2013","journal-title":"Cell. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"905","DOI":"10.3109\/1040841X.2015.1091805","article-title":"Vulvovaginal candidiasis: Epidemiology, microbiology and risk factors","volume":"42","author":"Goncalves","year":"2016","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ajog.2015.06.067","article-title":"Recurrent vulvovaginal candidiasis","volume":"214","author":"Sobel","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S1286-4579(00)00313-0","article-title":"Role played by lactobacilli in controlling the population of vaginal pathogens","volume":"2","author":"Boris","year":"2000","journal-title":"Microb. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5170","DOI":"10.1128\/IAI.67.10.5170-5175.1999","article-title":"Acid production by vaginal flora in vitro is consistent with the rate and extent of vaginal acidification","volume":"67","author":"Boskey","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0010-7824(99)00010-4","article-title":"A vaginal fluid simulant","volume":"59","author":"Owen","year":"1999","journal-title":"Contraception"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"O\u2019Hanlon, D., Moench, T., and Cone, R. (2013). Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080074"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6415","DOI":"10.1007\/s00253-016-7527-3","article-title":"Probiotic lactobacilli inhibit early stages of Candida albicans biofilm development by reducing their growth, cell adhesion, and filamentation","volume":"100","author":"Matsubara","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Liu, M., Xu, S., He, Y., Deng, G., Sheng, H., Huang, X., Ouyang, C., and Zhou, H. (2013). Diverse vaginal microbiomes in reproductive-age women with vulvovaginal candidiasis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079812"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15698\/mic2020.01.702","article-title":"The role of Lactobacillus species in the control of Candida via biotrophic interactions","volume":"7","author":"Zangl","year":"2020","journal-title":"Microb. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1080\/08927014.2017.1392514","article-title":"The carboxylic acid transporters Jen1 and Jen2 affect the architecture and fluconazole susceptibility of Candida albicans biofilm in the presence of lactate","volume":"33","author":"Alves","year":"2017","journal-title":"Biofouling"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.3389\/fmicb.2018.03265","article-title":"Effect of acetic acid and lactic acid at low pH in growth and azole resistance of Candida albicans and Candida glabrata","volume":"9","author":"Pedro","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1111\/j.1462-5822.2012.01813.x","article-title":"Host carbon surces modulate cell wall architecture, drug resistance and virulence in a fungal pathogen","volume":"14","author":"Ene","year":"2012","journal-title":"Cell Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5771","DOI":"10.3402\/jom.v3i0.5771","article-title":"Pathogenesis and treatment of oral candidosis","volume":"1","author":"Williams","year":"2011","journal-title":"J. Oral Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1073\/pnas.1117280109","article-title":"Amphotericin primarily kills yeast by simply binding ergosterol","volume":"109","author":"Gray","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Suchodolski, J., and Krasowska, A. (2021). Fructose induces fluconazole resistance in Candida albicans through activation of Mdr1 and Cdr1 transporters. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042127"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1128\/AAC.44.9.2296-2303.2000","article-title":"Transcriptional analyses of antifungal drug resistance in Candida albicans","volume":"44","author":"Lyons","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1089\/omi.2010.0072","article-title":"Adaptive response and tolerance to weak acids in Saccharomyces cerevisiae: A genome-wide view","volume":"14","author":"Mira","year":"2010","journal-title":"Omics J. Integr. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Suchodolski, J., Muraszko, J., Bernat, P., and 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.","DOI":"10.3390\/microorganisms7100378"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/yea.3455","article-title":"Lipid composition and cell surface hydrophobicity of Candida albicans influence the efficacy of fluconazole\u2013gentamicin treatment","volume":"37","author":"Suchodolski","year":"2020","journal-title":"Yeast"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-86012-9","article-title":"Capric acid secreted by Saccharomyces boulardii influences the susceptibility of Candida albicans to fluconazole and amphotericin B","volume":"11","author":"Suchodolski","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1128\/AAC.48.1.161-167.2004","article-title":"Fungicidal activity of fluconazole against Candida albicans in a synthetic vagina-simulative medium","volume":"48","author":"Moosa","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1099\/jmm.0.000082","article-title":"Antifungal activity of clotrimazole against Candida albicans depends on carbon sources, growth phase and morphology","volume":"64","author":"Kasper","year":"2015","journal-title":"J. Med. Microbiol."},{"key":"ref_26","first-page":"1","article-title":"Sugar sensing and signaling in Candida albicans and Candida glabrata","volume":"10","author":"Wijnants","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e00495-12","DOI":"10.1128\/mBio.00495-12","article-title":"The Evolutionary Rewiring of Ubiquitination Targets Has Reprogrammed the Regulation of Carbon Assimilation in the Pathogenic Yeast Candida albicans","volume":"3","author":"Sandai","year":"2012","journal-title":"MBio"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3064","DOI":"10.1128\/AAC.48.8.3064-3079.2004","article-title":"Comparison of gene expression profiles of Candida albicans azole-resistant clinical isolates and laboratory strains exposed to drugs inducing multidrug transporters","volume":"48","author":"Karababa","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1093\/jac\/dkh456","article-title":"Regulated overexpression of CDR1 in Candida albicans confers multidrug resistance","volume":"54","author":"Niimi","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1128\/AAC.48.4.1136-1144.2004","article-title":"The Candida albicans Lanosterol 14-\u03b1-Demethylase (ERG11) Gene Promoter Is Maximally Induced after Prolonged Growth with Antifungal Drugs","volume":"48","author":"Song","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11274-019-2673-2","article-title":"Outline of the biosynthesis and regulation of ergosterol in yeast","volume":"35","author":"Liu","year":"2019","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"M\u00fcller, C., Neugebauer, T., Zill, P., Lass-Fl\u00f6rl, C., Bracher, F., and Binder, U. (2018). Sterol composition of clinically relevant Mucorales and changes resulting from posaconazole treatment. Molecules, 23.","DOI":"10.3390\/molecules23051218"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.1128\/AAC.00348-10","article-title":"Identification and characterization of four azole-resistant erg3 mutants of Candida albicans","volume":"54","author":"Martel","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1128\/AAC.01664-10","article-title":"Effect of antibiotic treatment on the intestinal metabolome","volume":"55","author":"Antunes","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/jvim.14875","article-title":"The gastrointestinal microbiome: A review","volume":"32","author":"Barko","year":"2018","journal-title":"J. Vet. Int. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.micinf.2010.04.010","article-title":"Lactic acid bacteria colonization and clinical outcome after probiotic supplementation in conventionally treated bacterial vaginosis and vulvovaginal candidiasis","volume":"12","author":"Daroczy","year":"2010","journal-title":"Microb. Infect."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/genetics\/134.3.717","article-title":"Isogenic Strain Construction and Gene Mapping in Candida albicans","volume":"134","author":"Fonzi","year":"1993","journal-title":"Genetics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1128\/AAC.40.10.2300","article-title":"Susceptibilities of Candida albicans Multidrug Transporter Mutants to Various Antifungal Agents and Other Metabolic Inhibitors","volume":"40","author":"Sanglard","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1099\/00221287-143-2-405","article-title":"Cloning of Candida albicans genes conferring resistance to azole antifungal agents: Characterization of CDR2, a new multidrug ABC transporter gene","volume":"143","author":"Sanglard","year":"1997","journal-title":"Microbiology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.3389\/fmicb.2015.01382","article-title":"Estimation of Candida albicans ABC Transporter Behavior in Real-Time via Fluorescence","volume":"6","author":"Szczepaniak","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1083\/jcb.128.5.779","article-title":"A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast","volume":"128","author":"Vida","year":"1995","journal-title":"J. Cell Biol."},{"key":"ref_42","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":"Szczepaniak","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Suchodolski, J., Derkacz, D., Muraszko, J., Panek, J.J., and Jezierska, A. (2020). Fluconazole and Lipopeptide Surfactin Interplay During Candida albicans Plasma Membrane and Cell Wall Remodeling Increases Fungal Immune System Exposure. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12040314"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1194\/jlr.M078600","article-title":"Analysis of sphingolipids, sterols, and phospholipids in human pathogenic Cryptococcus strains","volume":"58","author":"Singh","year":"2017","journal-title":"J. Lipid Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/10\/5219\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:01:04Z","timestamp":1760162464000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/10\/5219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,14]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22105219"],"URL":"https:\/\/doi.org\/10.3390\/ijms22105219","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,14]]}}}