Genomic and transcriptome identification of fluconazole-resistant genes for Trichosporon asahii.
Med Mycol
; 58(3): 393-400, 2020 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-31504756
ABSTRACT
Trichosporon asahii infection is difficult to control clinically. This study identified a case with over 15 years of T. asahii infection-related systemic dissemination disease and conducted genome and transcriptome sequencing to identify fluconazole-resistant genes in fluconazole-resistant versus susceptible strains isolated from this patient's facial skin lesions. The data revealed mutations of the ergosterol biosynthetic pathway-related genes in the T. asahii genome of the fluconazole-resistant strain, that is, there were 36 novel mutations of the ERG11 gene, three point mutations (V458L, D457V, and D334S) in the ERG3, and a missense mutation (E349D) in ERG5 in the fluconazole-resistant strain of the T. asahii genome. To ensure that ERG11 is responsible for the fluconazole resistance, we thus simultaneously cultured the strains in vitro and cloned the ERG11 CDS sequences of both fluconazole-susceptible and -resistant strains into the Saccharomyces cerevisiae. These experiments confirmed that these mutations of ERG11 gene affected fluconazole resistance (> 64 µg/ml vs. <8 µg/ml of the MIC value between fluconazole-resistant and -susceptible strains) in Saccharomyces cerevisiae. In addition, expression of ergosterol biosynthesis pathway genes and drug transporter was upregulated in the fluconazole-resistant strain of T. asahii. Collectively, the fluconazole resistance in this female patient was associated with mutations of ERG11, ERG3, and ERG5 and the differential expression of drug transporter and fatty acid metabolic genes.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Trichosporon
/
Proteínas Fúngicas
/
Fluconazol
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Farmacorresistencia Fúngica
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Antifúngicos
Tipo de estudio:
Diagnostic_studies
Límite:
Adult
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Female
/
Humans
Idioma:
En
Revista:
Med Mycol
Asunto de la revista:
MEDICINA VETERINARIA
/
MICROBIOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China