Altered expression of selectable marker URA3 in gene-disrupted Candida albicans strains complicates interpretation of virulence studies

Jennifer Lay, L. Keith Henry, Julie Clifford, Yigal Koltin, Christine E. Bulawa, Jeffrey M. Becker

Research output: Contribution to journalArticlepeer-review

Abstract

The ura-blaster technique for the disruption of Candida albicans genes has been employed in a number of studies to identify possible genes encoding virulence factors of this fungal pathogen. In this study, the URA3-encoded orotidine 5'-monophosphate (OMP) decarboxylase enzyme activities of C. albicans strains with urablaster-mediated genetic disruptions were measured. All strains harboring genetic lesions via the ura-blaster construct showed reduced OMP decarboxylase activities compared to that of the wild type when assayed. The activity levels in different gene disruptions varied, suggesting a positional effect on the level of gene expression. Because the URA3 gene of C. albicans has previously been identified as a virulence factor for this microorganism, our results suggest that decreased virulence observed in strains constructed with the ura-blaster cassette cannot accurately be attributed, in all cases, to the targeted genetic disruption. Although revised methods for validating a URA3-disrupted gene as a target for antifungal drug development could be devised, it is clearly desirable to replace URA3 with a different selectable marker that does not influence virulence.

Original languageEnglish
Pages (from-to)5301-5306
Number of pages6
JournalInfection and Immunity
Volume66
Issue number11
DOIs
StatePublished - 1998
Externally publishedYes

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