2026-04-29T19:34:50Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/119872025-06-03T17:53:28Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Lucio, Jose
author
Gonzalez-Jimenez, Irene
author
Rivero-Menendez, Olga
author
Alastruey-Izquierdo, Ana
author
Pelaez, Teresa
author
Alcazar-Fuoli, Laura
author
Mellado, Emilia
funder
Instituto de Salud Carlos III
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
RETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
2021-02-26T08:41:58Z
2021-02-26T08:41:58Z
2020-10-17
Genes (Basel) . 2020 Oct 17;11(10):1217.
10.3390/genes11101217
2073-4425
Genes
33080784
http://hdl.handle.net/20.500.12105/11987
Infections caused by Aspergillus species are being increasingly reported. Aspergillus flavus is the second most common species within this genus causing invasive infections in humans, and isolates showing azole resistance have been recently described. A. flavus has three cyp51-related genes (cyp51A, cyp51B, and cyp51C) encoding 14-α sterol demethylase-like enzymes which are the target of azole drugs. In order to study triazole drug resistance in A. flavus, three strains showing reduced azole susceptibility and 17 azole susceptible isolates were compared. The three cyp51-related genes were amplified and sequenced. A comparison of the deduced Cyp51A, Cyp51B, and Cyp51C protein sequences with other protein sequences from orthologous genes in different filamentous fungi led to a protein identity that ranged from 50% to 80%. Cyp51A and Cyp51C presented several synonymous and non-synonymous point mutations among both susceptible and non-susceptible strains. However, two amino acid mutations were present only in two resistant isolates: one strain harbored a P214L substitution in Cyp51A, and another a H349R in Cyp51C that also showed an increase of cyp51A and cyp51C gene expression compared to the susceptible strain ATCC2004304. Isolates that showed reduced in vitro susceptibility to clinical azoles exhibited a different susceptibility profile to demethylation inhibitors (DMIs). Although P214L substitution might contribute to azole resistance, the role of H349R substitution together with changes in gene expression remains unclear.
eng
Aspergillus flavus
Cyp51s
DMIs fungicides
Azole resistance mechanisms
Azole drug
Point Mutations in the 14-α Sterol Demethylase Cyp51A or Cyp51C Could Contribute to Azole Resistance in Aspergillus flavus.
research article
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