Amino acid substitution in <i>Cryptococcus neoformans</i> lanosterol 14-α-demethylase involved in fluconazole resistance in clinical isolates

The molecular basis of fluconazole resistance in <i>Cryptococcus neoformans</i> has been poorly studied. A common azole resistance mechanism in <i>Candida</i> species is the acquisition of point mutations in the <i>ERG11</i> gene encoding the enzyme lanosterol 14-...

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Autores principales: Bosco Borgeat, María E., Mazza, Mariana, Taverna, Constanza G., Córdoba, Susana Beatriz, Murisengo, Omar A., Vivot, Walter, Davel, Graciela
Formato: Articulo
Lenguaje:Inglés
Publicado: 2016
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/106345
https://www.sciencedirect.com/science/article/pii/S0325754116300013
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Sumario:The molecular basis of fluconazole resistance in <i>Cryptococcus neoformans</i> has been poorly studied. A common azole resistance mechanism in <i>Candida</i> species is the acquisition of point mutations in the <i>ERG11</i> gene encoding the enzyme lanosterol 14-α-demethylase, target of the azole class of drugs. In <i>C. neoformans</i> only two mutations were described in this gene. In order to evaluate other mutations that could be implicated in fluconazole resistance in <i>C. neoformans</i> we studied the genomic sequence of the <i>ERG11</i> gene in 11 clinical isolates with minimal inhibitory concentration (MIC) values to fluconazole of ≥16 μg/ml. The sequencing revealed the G1855A mutation in 3 isolates, resulting in the enzyme amino acid substitution G484S. These strains were isolated from two fluconazole-treated patients. This mutation would not intervene in the susceptibility to itraconazole and voriconazole.