An aureobasidin A resistance gene isolated from Aspergillus is a homolog of yeast AUR1, a gene responsible for inositol phosphorylceramide (IPC) synthase activity

Abstract

The AUR1 gene of Saccharomyces cerevisiae, mutations in which confer resistance to the antibiotic aureobasidin A, is necessary for inositol phosphorylceramide (IPC) synthase activity. We report the molecular cloning and characterization of the Aspergillus nidulans aurA gene, which is homologous to AUR1. A single point mutation in the aurA gene of A. nidulans confers a high level of resistance to aureobasidin A. The A. nidulans aurA gene was used to identify its homologs in other Aspergillus species, including A. fumigatus, A. niger, and A. oryzae. The deduced amino acid sequence of an aurA homolog from the pathogenic fungus A. fumigatus showed 87% identity to that of A. nidulans. The AurA proteins of A. nidulans and A. fumigatus shared common characteristics in primary structure, including sequence, hydropathy profile, and N-glycosylation sites, with their S. cerevisiae, Schizosaccharomyces pombe, and Candida albicans counterparts. These results suggest that the aureobasidin resistance gene is conserved evolutionarily in various fungi.

Inhibition of yeast inositol phosphorylceramide synthase by aureobasidin A measured by a fluorometric assay

“…The fungicidal action of aureobasidin A, a feature highly desirable for the treatment of opportunistic fungal infections, has been suggested to be due to ceramide accumulation [6]. Significantly, the IPC synthase ( AUR1 ) gene has been identified in a wide range of fungi including two key opportunistic human pathogens: Candida albicans and Aspergillus fumigatus [16]. Thus, IPC synthase inhibitors are potentially broad‐spectrum antifungals.…”

Analysis of sphingolipids, sterols, and phospholipids in human pathogenic Cryptococcus strains

“…Pathways of sphingolipid biosynthesis and genes involved therein are well-characterized in several fungi, such as S. cereviseae, Aspergillus fumigatus, Aspergillus nidulans, C. albicans, Pichia pastoris, and others (34,37,(47)(48)(49)(50)(51)(52)(53)(54). In one example of P. pastoris, the pathway of GlcCer biosynthesis very closely fits with the pathway present in Cryptococcus (19,21,54).…”

“…Further, both PhytoCer and OHPhytoCer structures can be converted to IPC structures by transfer of a phosphorylinositol group (23). Although the IPC structures and pathway of synthesis have been characterized in several fungi (36,(48)(49)(50)(51)(52)(53)(54), they remain poorly studied in Cryptococcus (23). In our MRM analysis (positive ion mode), we scanned for 28 IPC structures ( low-level IPC structures (IPC derivatives 2 and 3A).…”

Aspergillus nidulans HOG pathway is activated only by two‐component signalling pathway in response to osmotic stress

“…A fragment containing the glaA142 promoter and agdA terminator was obtained from pNGA142 (Minetoki et al ., 1998) by digestion with Pst I and Sma I, and ligated into the same sites of the pUC/HE‐linker, resulting in pUC142. Then the fragment containing the glaA142 promoter and agdA terminator was obtained from pUC142 by digestion with Bam HI and ligated into the Bam HI site of pAUR316, which has the AMA1 replication origin (Gems et al ., 1991; Aleksenko et al ., 1996) and the Aureobasidin A resistance gene (Kuroda et al ., 1998), resulting in pAUR142. We confirmed that pAUR142 was available as an expression plasmid and succeeded in expressing of various proteins (our unpublished data).…”