Overexpression of a cloned IMP dehydrogenase gene of Candida albicans confers resistance to the specific inhibitor mycophenolic acid

Gerwald Koehler, Theodore C. White, Nina Agabian

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

An IMP dehydrogenase gene was isolated from Candida albicans on a ~2.9- kb XbaI genomic DNA fragment. The putative Candida IMP dehydrogenase gene (IMH3) encodes a protein of 521 amino acids with extensive sequence similarity to the IMP dehydrogenases of Saccharomyces cerevisiae and various other organisms. Like the S. cerevisiae IMH3 sequence characterized in the genome sequencing project, the open reading frame of the C. albicans IMH3 gene is interrupted by a small intron (248 bp) with typical exon-intron boundaries and a consensus S. cerevisiae branchpoint sequence. IMP dehydrogenase mRNAs are detected in both the yeast and hyphal forms of C. albicans as judged by Northern hybridization. Growth of wild-type (sensitive) C. albicans cells is inhibited at 1 μg of mycophenolic acid (MPA), a specific inhibitor of IMP dehydrogenases, per ml, whereas transformants hosting a plasmid with the IMH3 gene are resistant to MPA levels of up to at least 40 μg/ml. The resistance of cells to MPA is gene dosage dependent and suggests that IMH3 can be used as a dominant selection marker in C. albicans.

Original languageEnglish
Pages (from-to)2331-2338
Number of pages8
JournalJournal of Bacteriology
Volume179
Issue number7
DOIs
StatePublished - 1 Jan 1997

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IMP Dehydrogenase
Mycophenolic Acid
Candida albicans
Saccharomyces cerevisiae
Genes
Introns
Gene Dosage
Candida
Open Reading Frames
Exons
Plasmids
Yeasts
Genome
Amino Acids
Messenger RNA
DNA
Growth
Proteins

Cite this

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abstract = "An IMP dehydrogenase gene was isolated from Candida albicans on a ~2.9- kb XbaI genomic DNA fragment. The putative Candida IMP dehydrogenase gene (IMH3) encodes a protein of 521 amino acids with extensive sequence similarity to the IMP dehydrogenases of Saccharomyces cerevisiae and various other organisms. Like the S. cerevisiae IMH3 sequence characterized in the genome sequencing project, the open reading frame of the C. albicans IMH3 gene is interrupted by a small intron (248 bp) with typical exon-intron boundaries and a consensus S. cerevisiae branchpoint sequence. IMP dehydrogenase mRNAs are detected in both the yeast and hyphal forms of C. albicans as judged by Northern hybridization. Growth of wild-type (sensitive) C. albicans cells is inhibited at 1 μg of mycophenolic acid (MPA), a specific inhibitor of IMP dehydrogenases, per ml, whereas transformants hosting a plasmid with the IMH3 gene are resistant to MPA levels of up to at least 40 μg/ml. The resistance of cells to MPA is gene dosage dependent and suggests that IMH3 can be used as a dominant selection marker in C. albicans.",
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Overexpression of a cloned IMP dehydrogenase gene of Candida albicans confers resistance to the specific inhibitor mycophenolic acid. / Koehler, Gerwald; White, Theodore C.; Agabian, Nina.

In: Journal of Bacteriology, Vol. 179, No. 7, 01.01.1997, p. 2331-2338.

Research output: Contribution to journalArticle

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