2024-03-28T13:29:48Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/116502023-10-10T12:23:59Zcom_20.500.12105_2060com_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_2061
00925njm 22002777a 4500
dc
Gonzalez-Jimenez, Irene
author
Lucio, Jose
author
Amich, Jorge
author
Cuesta de la Plaza, Isabel
author
Sanchez Arroyo, Rafael
author
Alcazar-Fuoli, Laura
author
Mellado, Emilia
author
2020-11-26
The emergence and spread of Aspergillus fumigatus azole resistance has been acknowledged worldwide. The main problem of azole resistance is the limited therapeutic options for patients suffering aspergillosis. Azole resistance mechanisms have been mostly linked to the enzyme Cyp51A, a target of azole drugs, with a wide variety of modifications responsible for the different resistance mechanisms described to date. However, there are increasing reports of A. fumigatus strains showing azole resistance without Cyp51A modifications, and thus, novel resistance mechanisms are being explored. Here, we characterized two isogenic A. fumigatus clinical strains isolated two years apart from the same patient. Both strains were resistant to clinical azoles but showed different azole resistance mechanisms. One strain (CM8940) harbored a previously described G54A mutation in Cyp51A while the other strain (CM9640) had a novel G457S mutation in Cyp51B, the other target of azoles. In addition, this second strain had a F390L mutation in Hmg1. CM9640 showed higher levels of gene expression of cyp51A, cyp51B and hmg1 than the CM8940 strain. The role of the novel mutation found in Cyp51B together with the contribution of a mutation in Hmg1 in azole resistance is discussed.
J Fungi (Basel) . 2020 Nov 26;6(4):315.
http://hdl.handle.net/20.500.12105/11650
33255951
10.3390/jof6040315
2309-608X
Journal of fungi (Basel, Switzerland)
Aspergillus fumigatus
Cyp51B
Azole resistance
Cyp51A
Hmg1
A Cyp51B Mutation Contributes to Azole Resistance in Aspergillus fumigatus.