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However, in the last decade the rate of azole resistance among\n            <jats:named-content content-type=\"genus-species\">Aspergillus fumigatus<\/jats:named-content>\n            strains has increased notoriously. The main resistance mechanisms are well defined and mostly related to point mutations of the azole target, 14-\u03b1 sterol demethylase (\n            <jats:italic>cyp51A<\/jats:italic>\n            ), with or without tandem repeat integrations in the\n            <jats:italic>cyp51A<\/jats:italic>\n            promoter. Furthermore, different combinations of five Cyp51A mutations (F46Y, M172V, N248T, D255E, and E427K) have been reported worldwide in about 10% of all\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            isolates tested. The azole susceptibility profile of these strains shows elevated azole MICs, although on the basis of the azole susceptibility breakpoints, these strains are not considered azole resistant. The purpose of the study was to determine whether these\n            <jats:italic>cyp51A<\/jats:italic>\n            polymorphisms (single nucleotide polymorphisms [SNPs]) are responsible for the azole susceptibility profile and whether they are reflected in a poorer azole treatment response\n            <jats:italic>in vivo<\/jats:italic>\n            that could compromise patient treatment and outcome. A mutant with a\n            <jats:italic>cyp51A<\/jats:italic>\n            deletion was generated and became fully susceptible to all azoles tested. Also, three\n            <jats:italic>cyp51A<\/jats:italic>\n            gene constructions with different combinations of SNPs were generated and reintroduced into an azole-susceptible wild-type (WT) strain (the \u0394\n            <jats:italic>akuB<\/jats:italic>\n            <jats:sup>KU80<\/jats:sup>\n            strain). The alternative model host\n            <jats:named-content content-type=\"genus-species\">Galleria mellonella<\/jats:named-content>\n            was used to compare the virulence and voriconazole response of\n            <jats:named-content content-type=\"genus-species\">G. mellonella<\/jats:named-content>\n            larvae infected with\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            strains with WT\n            <jats:italic>cyp51A<\/jats:italic>\n            or\n            <jats:italic>cyp51A<\/jats:italic>\n            with SNPs. All strains were pathogenic in\n            <jats:named-content content-type=\"genus-species\">G. mellonella<\/jats:named-content>\n            larvae, although they did not respond similarly to voriconazole therapeutic doses. Finally, the full genomes of these strains were sequenced and analyzed in comparison with those of\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            WT strains, revealing that they belong to different strain clusters or lineages.\n          <\/jats:p>","DOI":"10.1128\/aac.00241-18","type":"journal-article","created":{"date-parts":[[2018,4,6]],"date-time":"2018-04-06T09:45:30Z","timestamp":1523007930000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":57,"title":["Insight into the Significance of Aspergillus fumigatus cyp51A Polymorphisms"],"prefix":"10.1128","volume":"62","author":[{"given":"Rocio","family":"Garcia-Rubio","sequence":"first","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Alcazar-Fuoli","sequence":"additional","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain"},{"name":"Spanish Network for Research in Infectious Diseases (REIPI RD16\/0016), ISCIII, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Candida","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Monzon","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit, Common Scientific Technical Units, ISCIII, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Cuesta","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit, Common Scientific Technical Units, ISCIII, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Pelaez","sequence":"additional","affiliation":[{"name":"Hospital Universitario Central de Asturias, Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria del Principado de Asturias (FINBA), Oviedo, Asturias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Mellado","sequence":"additional","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain"},{"name":"Spanish Network for Research in Infectious Diseases (REIPI RD16\/0016), ISCIII, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.12.2.310"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-014-0722-7"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01382"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-017-0714-4"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01358-10"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05990-11"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2106.140717"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00156-08"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1507.090043"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00231-09"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq279"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1710.110226"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt071"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00536-15"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00428"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/myc.12324"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2008.02086.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00940-09"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2009.09.002"},{"key":"e_1_3_3_21_2","doi-asserted-by":"crossref","unstructured":"Prigitano A Venier V Cogliati M De Lorenzis G Esposto MC Tortorano AM. 2014. 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