{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:48:45Z","timestamp":1790516925227,"version":"4.1.0"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"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":[[2015,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Candida parapsilosis<\/jats:named-content>\n is the main non-\n albicans Candida<\/jats:named-content>\n species isolated from patients in Latin America. Mutations in the\n ERG11<\/jats:italic>\n gene and overexpression of membrane transporter proteins have been linked to fluconazole resistance. The aim of this study was to evaluate the molecular mechanisms in fluconazole-resistant strains of\n C. parapsilosis<\/jats:named-content>\n isolated from critically ill patients. The identities of the nine collected\n C. parapsilosis<\/jats:named-content>\n isolates at the species level were confirmed through molecular identification with a TaqMan qPCR assay. The clonal origin of the strains was checked by microsatellite typing. The\n Galleria mellonella<\/jats:named-content>\n infection model was used to confirm\n in vitro<\/jats:italic>\n resistance. We assessed the presence of\n ERG11<\/jats:italic>\n mutations, as well as the expression of\n ERG11<\/jats:italic>\n and two additional genes that contribute to antifungal resistance (\n CDR1<\/jats:italic>\n and\n MDR1<\/jats:italic>\n ), by using real-time quantitative PCR. All of the\n C. parapsilosis<\/jats:named-content>\n (\n sensu stricto<\/jats:named-content>\n ) isolates tested exhibited fluconazole MICs between 8 and 16 \u03bcg\/ml. The\n in vitro<\/jats:italic>\n data were confirmed by the failure of fluconazole in the treatment of\n G. mellonella<\/jats:named-content>\n infected with fluconazole-resistant strains of\n C. parapsilosis<\/jats:named-content>\n . Sequencing of the\n ERG11<\/jats:italic>\n gene revealed a common mutation leading to a Y132F amino acid substitution in all of the isolates, a finding consistent with their clonal origin. After fluconazole exposure, overexpression was noted for\n ERG11<\/jats:italic>\n ,\n CDR1<\/jats:italic>\n , and\n MDR1<\/jats:italic>\n in 9\/9, 9\/9, and 2\/9 strains, respectively. We demonstrated that a combination of molecular mechanisms, including the presence of point mutations in the\n ERG11<\/jats:italic>\n gene, overexpression of\n ERG11<\/jats:italic>\n , and genes encoding efflux pumps, are involved in fluconazole resistance in\n C. parapsilosis<\/jats:named-content>\n .\n <\/jats:p>","DOI":"10.1128\/aac.01177-15","type":"journal-article","created":{"date-parts":[[2015,8,11]],"date-time":"2015-08-11T02:20:26Z","timestamp":1439259626000},"page":"6581-6587","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":117,"title":["Candida parapsilosis Resistance to Fluconazole: Molecular Mechanisms and\n In Vivo<\/i>\n Impact in Infected Galleria mellonella Larvae"],"prefix":"10.1128","volume":"59","author":[{"given":"Ana Carolina R.","family":"Souza","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio Especial de Micologia, Disciplina de Infectologia, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth Burgwyn","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique M. S.","family":"Pinhati","sequence":"additional","affiliation":[{"name":"Universidade de Bras\u00edlia, Bras\u00edlia, DF, Brazil"},{"name":"Hospital Santa Luzia, Bras\u00edlia, DF, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo A.","family":"Siqueira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Especial de Micologia, Disciplina de Infectologia, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferry","family":"Hagen","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques F.","family":"Meis","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, Netherlands"},{"name":"Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4624-0777","authenticated-orcid":false,"given":"Eleftherios","family":"Mylonakis","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaldo L.","family":"Colombo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Especial de Micologia, Disciplina de Infectologia, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00013-08"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e3182863a1c"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.riam.2013.10.001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.4.1829-1835.2005"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-6-21"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00773-06"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01998-13"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059373"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02670-14"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101510"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.2.767-769.2005"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.6.2729-2735.2005"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00466-11"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis697"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00308-13"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/myc.12206"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/596757"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjid.2013.02.001"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.2.279"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.11.2378"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.12.2835"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2004.04.009"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a019752"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01102-09"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/42.2.241"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1324245111"},{"key":"e_1_3_2_28_2","volume-title":"Abstr 53th Intersci Conf Antimicrob Agents Chemother","author":"Pinhati HM","year":"2013","unstructured":"Pinhati HM, Casulari LA, Bizerra FC, Siqueira RA, Castro FF, Colombo AL. 2013. 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