Association of ergot alkaloids with conidiation inAspergillus fumigatus

Abstract

Ergot alkaloids are mycotoxins that affect the nervous and reproductive systems of exposed individuals through interactions with monoamine receptors. They have been studied more widely in ergot fungi and grass endophytes but also are found in Aspergillus fumigatus, an opportunistic human pathogen that reproduces and disseminates exclusively through conidia. The ergot alkaloids festuclavine and fumigaclavines A, B and C are present in or on conidia of A. fumigatus. Cultures of the fungus that are free of conidia are difficult to obtain, obscuring comparisons of conidia versus vegetative hyphae as sources of the ergot alkaloids. To create conidiation-deficient strains of A. fumigatus we manipulated the bristle A gene (brlA), which controls vesicle formation or budding growth necessary for conidiation in Aspergillus spp. Disruption of brlA in A. fumigatus, via homologous recombination, resulted in a nonconidiating mutant that produced bristle-like structures instead of conidiophores and conidia. Moreover the disrupted strain failed to produce ergot alkaloids as verified by HPLC analyses. Complementation with a wild-type allele restored conidiation and ergot alkaloid production. These results suggest that ergot alkaloids are not produced within the vegetative mycelium of the fungus and are associated directly with conidiation.

Transcriptional Profiling Identifies a Role for BrlA in the Response to Nitrogen Depletion and for StuA in the Regulation of Secondary Metabolite Clusters in Aspergillus fumigatus

“…CELL clavine) exhibited BrlAp dependence for the expression of its genes. These data are consistent with the observation that the ⌬brlA mutant strain is deficient in the production of ergot alkaloids (11). Since conidiation is abrogated in the ⌬brlA strain yet secondary metabolism is relatively unaffected, these data highlight that conidiation is not an absolute requirement for the elaboration of many of the products of secondary metabolism.…”

“…Generally, developmental transcription factors often regulate secondary metabolism. For example, A. fumigatus brlA mutants are defective in the production of some members of the ergot alkaloid class of secondary metabolites, specifically, fumigaclavines A, B, and C (11). The expression of the epipolythiodioxopiperazine (ETP) gliotoxin, which induces host cell apoptosis and is required for normal virulence of A. fumigatus, is dependent on StuAp both in vitro and in vivo (16,17,29,32,35).…”

Nonribosomal Peptide Synthetase Genes pesL and pes1 Are Essential for Fumigaclavine C Production in Aspergillus fumigatus

“…strain. A complete loss of fumigaclavine C in the A. fumigatus ⌬pesL strain was observed wherein conidia, in part, comprised the specimens under examination, in agreement with the known EA association with A. fumigatus conidia (10). Furthermore, fumigaclavine C was also completely absent in metabolite extracts of A. fumigatus ⌬pes1, suggesting redundancy among these NRP synthetases.…”

Heat Shock Protein 90 Is Required for Conidiation and Cell Wall Integrity in Aspergillus fumigatus

“…To assess Hsp90 repression in the pniiA-Hsp90 strain, hsp90 expression was measured under repression conditions (AMM) and compared to the expression level in the akuB KU80 control strain. In order to investigate the link between Hsp90 and conidiation, the expression of the brlA, abaA, and wetA genes, known to be involved in conidial formation (10,35), was assessed. Expression of hsp90 was also measured in the wild-type (AF293) under basal and various stress conditions to assess the role of Hsp90 in various stress response mechanisms.…”

“…Because of the severe conidiation defect under Hsp90 repression, we quantified the expression of brlA, abaA, and wetA, three genes encoding transcription factors that are known to control asexual sporulation in Aspergillus species (10,35). Compared with the akuB KU80 strain, pniiA-Hsp90 under repression exhibited a significant decrease in the expression of brlA (70.2-Ϯ 5.5-fold decrease; P ϭ 0.0004), abaA (7.8-Ϯ 2.6-fold decrease; P ϭ 0.008), and wetA (4.5-Ϯ 1.4-fold decrease; P ϭ 0.003) (Fig.…”