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dc.contributor.authorGonzalez-Jimenez, Irene 
dc.contributor.authorLucio, Jose 
dc.contributor.authorRoldán, Alejandra 
dc.contributor.authorAlcazar-Fuoli, Laura 
dc.contributor.authorMellado, Emilia
dc.identifier.citationMolecules. 2021 Oct 1;26(19):5975.es_ES
dc.description.abstractInvasive aspergillosis, mainly caused by Aspergillus fumigatus, can lead to severe clinical outcomes in immunocompromised individuals. Antifungal treatment, based on the use of azoles, is crucial to increase survival rates. However, the recent emergence of azole-resistant A. fumigatus isolates is affecting the efficacy of the clinical therapy and lowering the success rate of azole strategies against aspergillosis. Azole resistance mechanisms described to date are mainly associated with mutations in the azole target gene cyp51A that entail structural changes in Cyp51A or overexpression of the gene. However, strains lacking cyp51A modifications but resistant to clinical azoles have recently been detected. Some genes have been proposed as new players in azole resistance. In this study, the gene hmg1, recently related to azole resistance, and its paralogue hmg2 were studied in a collection of fifteen azole-resistant strains without cyp51A modifications. Both genes encode HMG-CoA reductases and are involved in the ergosterol biosynthesis. Several mutations located in the sterol sensing domain (SSD) of Hmg1 (D242Y, G307D/S, P309L, K319Q, Y368H, F390L and I412T) and Hmg2 (I235S, V303A, I312S, I360F and V397C) were detected. The role of these mutations in conferring azole resistance is discussed in this work.es_ES
dc.description.sponsorshipThis research was funded by Fondo de Investigacion Sanitaria (FIS PI18CIII/00045) and also by Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/CIII/0004/0003), co-financed by European Development Regional Fund ERDF “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020.es_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI) es_ES
dc.subjectAspergillus fumigatuses_ES
dc.subjectAzole resistance mechanismses_ES
dc.titleAre Point Mutations in HMG-CoA Reductases (Hmg1 and Hmg2) a Step towards Azole Resistance in Aspergillus fumigatus?es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España) es_ES
dc.contributor.funderInstituto de Salud Carlos III es_ES
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) es_ES
dc.contributor.funderRETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España) es_ES
dc.contributor.funderPlan Nacional de I+D+i (España) es_ES
dc.identifier.journalMolecules (Basel, Switzerland)es_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.rights.accessRightsopen accesses_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/REIPI RD16/CIII/0004/0003es_ES
dc.relation.projectFISinfo:fis/Instituto de Salud Carlos III/Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia/Subprograma Estatal de Generación de Conocimiento/PI18-ISCIII Modalidad Proyectos de Investigacion en Salud Intramurales. (2018)/PI18CIII/00045es_ES

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Atribución 4.0 Internacional
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