{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:40:19Z","timestamp":1790991619636,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS PI18\/CIII\/00045"],"award-info":[{"award-number":["FIS PI18\/CIII\/00045"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["REIPI RD16\/CIII\/0004\/0003"],"award-info":[{"award-number":["REIPI RD16\/CIII\/0004\/0003"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Invasive aspergillosis, mainly caused by Aspergillus\u00a0fumigatus, 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.<\/jats:p>","DOI":"10.3390\/molecules26195975","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T21:23:55Z","timestamp":1633728235000},"page":"5975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Are Point Mutations in HMG-CoA Reductases (Hmg1 and Hmg2) a Step towards Azole Resistance in Aspergillus fumigatus?"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4821-4852","authenticated-orcid":false,"given":"Irene","family":"Gonzalez-Jimenez","sequence":"first","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), 28220 Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7545-7510","authenticated-orcid":false,"given":"Jose","family":"Lucio","sequence":"additional","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), 28220 Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Roldan","sequence":"additional","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), 28220 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), 28220 Majadahonda, Madrid, Spain"},{"name":"Spanish Network for Research in Infectious Diseases (REIPI RD16\/CIII\/0004\/0003), ISCIII, 28220 Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-0260","authenticated-orcid":false,"given":"Emilia","family":"Mellado","sequence":"additional","affiliation":[{"name":"Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), 28220 Majadahonda, Madrid, Spain"},{"name":"Spanish Network for Research in Infectious Diseases (REIPI RD16\/CIII\/0004\/0003), ISCIII, 28220 Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Aspergillus fumigatus and aspergillosis","volume":"33","author":"Latge","year":"2020","journal-title":"Clin. 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