2026-07-21T08:25:00Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/259702025-12-18T12:59:53Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Lucio, Jose
author
Gonzalez-Jimenez, Irene
author
Roldán, Alejandra
author
Amich, Jorge
author
Alcazar-Fuoli, Laura
author
Mellado, Emilia
funder
Instituto de Salud Carlos III
funder
Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
2025-01-09T09:22:41Z
2025-01-09T09:22:41Z
2024-03-12
Lucio J, Gonzalez-Jimenez I, Roldan A, Amich J, Alcazar-Fuoli L, Mellado E. Importance of the Aspergillus fumigatus Mismatch Repair Protein Msh6 in Antifungal Resistance Development. J Fungi (Basel). 2024 Mar 12;10(3):210.
10.3390/jof10030210
2309-608X
Journal of fungi (Basel, Switzerland)
38535218
https://hdl.handle.net/20.500.12105/25970
One of the systems responsible for the recognition and repair of mistakes occurring during cell replication is the DNA mismatch repair (MMR) system. Two major protein complexes constitute the MMR pathway: MutS and MutL. Here, we investigated the possible relation of four MMR genes (2, 6, 1, and 1) with the development of azole resistance related to the phenomenon of multi-drug resistance. We examined the MMR gene variations in 163 genomes. Our analysis showed that genes 2, 1, and 1 have low genetic variability and do not seem to correlate with drug resistance. In contrast, there is a nonsynonymous mutation (G240A) in the 6 gene that is harbored by 42% of the strains, most of them also harboring the TR/L98H azole resistance mechanism in 51A. The 6 gene was deleted in the B strain, and the ∆6 isolates were analyzed for fitness, azole susceptibility, and virulence capacity, showing no differences compared with the B parental strain. Wild-type 6 and Δ6 strains were grown on high concentrations of azole and other non-azole fungicides used in crop protection. A 10- and 2-fold higher mutation frequency in genes that confer resistance to boscalid and benomyl, respectively, were observed in Δ6 strains compared to the wild-type. This study suggests a link between Msh6 and fungicide resistance acquisition.
eng
Aspergillus fumigatus
MMR pathway
Antifungal resistance
msh6
Importance of the Mismatch Repair Protein Msh6 in Antifungal Resistance Development
research article
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ImportanceAspergillusFumigatusMismatch_2024.pdf
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Supplementary_ImportanceAspergillusFumigatusMismatch_2024.pdf