2026-08-30T13:04:40Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/142562024-09-27T19:18:45Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Gonzalez-Jimenez, Irene
author
Lucio, Jose
author
Roldán, Alejandra
author
Alcazar-Fuoli, Laura
author
Mellado, Emilia
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
RETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España)
funder
Plan Nacional de I+D+i (España)
2022-05-05T08:57:03Z
2022-05-05T08:57:03Z
2021-10-01
Molecules. 2021 Oct 1;26(19):5975.
10.3390/molecules26195975
1420-3049
Molecules (Basel, Switzerland)
34641518
http://hdl.handle.net/20.500.12105/14256
Invasive 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.
eng
Aspergillus fumigatus
Azole resistance mechanisms
Cyp51A
Hmg1
Hmg2
Are Point Mutations in HMG-CoA Reductases (Hmg1 and Hmg2) a Step towards Azole Resistance in Aspergillus fumigatus?
research article
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ArePointMutationsIn_2021.pdf
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https://repisalud.isciii.es/bitstreams/13d20c14-bc50-476d-b69e-043409afb55c/download
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ArePointMutationsIn_2021.pdf.txt