Vandeputte P, et al. (2009) Hypersusceptibility to azole antifungals in a clinical isolate of Candida glabrata with reduced aerobic growth. Antimicrob Agents Chemother 53(7):3034-41
Abstract: Petite mutations have been described in Saccharomyces cerevisiae and in pathogenic yeasts. However, previous studies of phenotypic traits of these petite mutants reported that they express azole resistance. Here, we describe a clinical isolate of Candida glabrata with a striking association between increased susceptibility to azoles and respiratory deficiency. This isolate was obtained from a urine sample together with a respiratory-competent C. glabrata isolate which exhibited azole resistance. The respiratory status of the two isolates was confirmed by cultivation on glycerol-containing agar and oxygraphy. Flow cytometry revealed normal incorporation of rhodamine 123 and mitochondrial sections with typical cristae were seen by transmission electron microscopy for both isolates. Together these results suggested a nuclear origin for the reduced respiratory capacity of the hypersusceptible isolate. The sterol contents of these isolates were similar to that of a reference strain. Sequencing of the ERG11 and PDR1 genes revealed identical sequences for both isolates, demonstrating their close relatedness. In addition to silent mutations, they carried a nonsense mutation in PDR1 leading to the truncation of transcription factor Pdr1p. They also overexpressed both PDR1 and of one of its targets, CDR1, providing a possible explanation of the azole resistance of the respiratory-competent isolate. In conclusion, in addition to azole resistance which is a common feature of C. glabrata mitochondrial petite mutants, the mutation of a nuclear gene affecting aerobic growth may lead to azole hypersusceptibility; however, the mechanisms underlying this phenotype remain to be determined.
|Status: Published||Type: Journal Article||PubMed ID: 19380598|
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