Category
Basic
Description
The genus Aspergillus includes several species that are opportunistic pathogens, with members ranked in the World Health Organization’s fungal critical priority pathogen list. Aspergillus flavus, a member of the genus, synthesizes aflatoxin (AF), a polyketide mycotoxin and the most potent naturally occurring carcinogen known. aflR is a pathway-specific transcription factor that plays a central role in the regulatory network for AF biosynthesis. Transcriptomic analysis under AF-conducive and non-conducive conditions identified a cluster of genes with similar expression profiles to aflR. Among these is a putative Rho-GDP dissociation inhibitor that regulates AF production and virulence in A. flavus. Deletion of this gene, rdiA, results in increased septation intervals, altered hyphal branching, and a significant decrease in AF production. The phenotypes exhibited by the ¿rdiA mutant resemble both the rdi1¿ mutant in C. neoformans and the bem4¿ mutant in S. cerevisiae, including severe growth defects on minimal medium, moderate defects on complete medium, and cold sensitivity. Consistent with outcomes in C. neoformans, the A. flavus ¿rdiA mutant showed significantly attenuated virulence in an invertebrate infection model. To confirm the identity and function of the rdiA gene, we will complement the ¿rdiA mutant in A. flavus and assess the ability of the A. flavus rdiA gene to complement the rdi1¿ mutation in C. neoformans.
Characterization of the Aspergillus flavus rdiA Gene with a rdi1∆ Mutant of C. neoformans
Basic
The genus Aspergillus includes several species that are opportunistic pathogens, with members ranked in the World Health Organization’s fungal critical priority pathogen list. Aspergillus flavus, a member of the genus, synthesizes aflatoxin (AF), a polyketide mycotoxin and the most potent naturally occurring carcinogen known. aflR is a pathway-specific transcription factor that plays a central role in the regulatory network for AF biosynthesis. Transcriptomic analysis under AF-conducive and non-conducive conditions identified a cluster of genes with similar expression profiles to aflR. Among these is a putative Rho-GDP dissociation inhibitor that regulates AF production and virulence in A. flavus. Deletion of this gene, rdiA, results in increased septation intervals, altered hyphal branching, and a significant decrease in AF production. The phenotypes exhibited by the ¿rdiA mutant resemble both the rdi1¿ mutant in C. neoformans and the bem4¿ mutant in S. cerevisiae, including severe growth defects on minimal medium, moderate defects on complete medium, and cold sensitivity. Consistent with outcomes in C. neoformans, the A. flavus ¿rdiA mutant showed significantly attenuated virulence in an invertebrate infection model. To confirm the identity and function of the rdiA gene, we will complement the ¿rdiA mutant in A. flavus and assess the ability of the A. flavus rdiA gene to complement the rdi1¿ mutation in C. neoformans.
