Fluconazole resistance in C. parapsilosis, no evidence for ERG11 mutation

Abstract number: 1733_1456

Alkhalaf M.A., Dodgson K.J., Sarvikivi E., Dodgson A.R.

Objectives:C. parapsilosis is a well recognized cause of systemic infection in premature neonates, fortunately the isolates of this species demonstrate almost universal sensitivity to fluconazole. However, a 12 year clonal outbreak with a C. parapsilosis strain that developed fluconazole resistance has recently been described While many mechanisms of fluconazole resistance have been described in C. albicans, resistance mechanisms in C. parapsilosis have not been documented. We sequenced the ERG11 gene in a number of isolates from the outbreak to determine whether mutation in the target of fluconazole played a role in the development of resistance.

Methods: As only a fragment of the C. parapsilosis ERG11 gene is available in GenBank, we searched for fragments in the Genomic Sequence Survey database that displayed homology to C. albicans ERG11. These fragments were assembled to produce a template from which primers were designed. This putative CpERG11 gene was amplified and sequenced in seven isolates, representing fluconazole MIC's ranging from 0.5 to 64 ug/mL. Sequences obtained were compared to known ERG11 sequences and to each other to determine if any mutations were likely to contribute to resistance.

Results: Sequence was obtained in all seven isolates. Up to 1317 bp of the coding region of the putative CpERG11 was sequenced, comparison of the translated protein showed 73% identity and 86% similarity with C. albicans ERG11 (Accession no. XP716761) suggesting that the sequences obtained were indeed the C. parapsilosis ERG11 gene. However, no differences were detected in any of the sequences obtained.

Conclusions: Fluconazole resistance in other Candida species has been shown to be mediated by a number of mechanisms. Whilst upregulation of efflux pumps appears to be the most common mechanism of resistance in most species, mutations in the ERG11 gene that encodes the target of fluconazole has also been described. It appears that in the set of isolates used in this study, fluconazole resistance is not mediated by ERG11 mutations. A number of other possibilities such as ERG11 expression and efflux pump expression remain to be investigated.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Location: ICC, Munich, Germany
Presentation type:
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