Amino acid substitution in Cryptococcus neoformans lanosterol 14-α-demethylase involved in fluconazole resistance in clinical isolates.
The molecular basis of fluconazole resistance in Cryptococcus neoformans has been poorly studied. A common azole resistance mechanism in Candida species is the acquisition of point mutations in the ERG11 gene encoding the enzyme lanosterol 14-α-demethylase, target of the azole class of drugs. In C. neoformans only two mutations were described in this gene. In order to evaluate other mutations that could be implicated in fluconazole resistance in C. neoformans we studied the genomic sequence of the ERG11 gene in 11 clinical isolates with minimal inhibitory concentration (MIC) values to fluconazole of ≥16μg/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.
Departamento Micología, Instituto Nacional de Enfermedades Infecciosas "Dr. Carlos G. Malbrán", Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: ebosco@anlis.gov.ar.
María E
ME
Bosco-Borgeat
Departamento Micología, Instituto Nacional de Enfermedades Infecciosas "Dr. Carlos G. Malbrán", Ciudad Autónoma de Buenos Aires, Argentina.
Mariana
M
Mazza
Departamento Micología, Instituto Nacional de Enfermedades Infecciosas "Dr. Carlos G. Malbrán", Ciudad Autónoma de Buenos Aires, Argentina.
Constanza G
CG
Taverna
Departamento Micología, Instituto Nacional de Enfermedades Infecciosas "Dr. Carlos G. Malbrán", Ciudad Autónoma de Buenos Aires, Argentina.
Susana
S
Córdoba
Departamento Micología, Instituto Nacional de Enfermedades Infecciosas "Dr. Carlos G. Malbrán", Ciudad Autónoma de Buenos Aires, Argentina.
Omar A
OA
Murisengo
Departamento Micología, Instituto Nacional de Enfermedades Infecciosas "Dr. Carlos G. Malbrán", Ciudad Autónoma de Buenos Aires, Argentina.
Walter
W
Vivot
Departamento Micología, Instituto Nacional de Enfermedades Infecciosas "Dr. Carlos G. Malbrán", Ciudad Autónoma de Buenos Aires, Argentina.
Graciela
G
Davel
D019943:Amino Acid Substitution; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003453:Cryptococcosis / Q000188:drug therapy / Q000382:microbiology*; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D025141:Drug Resistance, Fungal / Q000235:genetics*; D015725:Fluconazole / Q000494:pharmacology* / Q000627:therapeutic use; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D016919:Meningitis, Cryptococcal / Q000188:drug therapy / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense; D017354:Point Mutation; D012008:Recurrence; D058886:Sterol 14-Demethylase / Q000235:genetics* / Q000502:physiology; D013329:Structure-Activity Relationship; D065819:Voriconazole / Q000494:pharmacology
D000935:Antifungal Agents; D005656:Fungal Proteins; D017964:Itraconazole; D015725:Fluconazole; D058886:Sterol 14-Demethylase; D065819:Voriconazole
Amino acid substitution; Cryptococcus neoformans; ERG11 gene; Fluconazole resistance; Gen ERG11; Mutación; Mutation; Resistencia al fluconazol; Sustitución aminoacídica