Reduced Susceptibility to Polyenes Associated with a Missense Mutation in the ERG6 Gene in a Clinical Isolate of Candida glabrata with Pseudohyphal Growth
You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
Reduced Susceptibility to Polyenes Associated with a Missense Mutation in the ERG6 Gene in a Clinical Isolate of Candida glabrata with Pseudohyphal Growth
Published:
American Society for Microbiology, 2007
Published in:
Antimicrobial Agents and Chemotherapy, 51 (2007) 3, Seite 982-990
Language:
English
DOI:
10.1128/aac.01510-06
ISSN:
0066-4804;
1098-6596
Origination:
Footnote:
Description:
ABSTRACT Little information is available about the molecular mechanisms responsible for polyene resistance in pathogenic yeasts. A clinical isolate of Candida glabrata with a poor susceptibility to polyenes, as determined by disk diffusion method and confirmed by determination of MIC, was recovered from a patient treated with amphotericin B. Quantitative analysis of sterols revealed a lack of ergosterol and an accumulation of late sterol intermediates, suggesting a defect in the final steps of the ergosterol pathway. Sequencing of Cg ERG11 , Cg ERG6 , Cg ERG5 , and Cg ERG4 genes revealed exclusively a unique missense mutation in Cg ERG6 leading to the substitution of a cysteine by a phenylalanine in the corresponding protein. In addition, real-time reverse transcription-PCR demonstrated an overexpression of genes encoding enzymes involved in late steps of the ergosterol pathway. Moreover, this isolate exhibited a pseudohyphal growth whatever the culture medium used, and ultrastructural changes of the cell wall of blastoconidia were seen consisting in a thinner inner layer. Cell wall alterations were also suggested by the higher susceptibility of growing cells to Calcofluor white. Additionally, complementation of this isolate with a wild-type copy of the Cg ERG6 gene restored susceptibility to polyenes and a classical morphology. Together, these results demonstrated that mutation in the Cg ERG6 gene may lead to a reduced susceptibility to polyenes and to a pseudohyphal growth due to the subsequent changes in sterol content of the plasma membrane.