Association of ergot alkaloids with conidiation in Aspergillus 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.

Analysis and Modification of Ergot Alkaloid Profiles in Fungi

“…In A. fumigatus, ergot alkaloids are produced in the asexual reproductive structures known as conidia and not in vegetative structures (Coyle, Kenaley, Rittenour, & Panaccione, 2007). Since the average mass of a conidium is 2.9 pg , the mass of conidia in an extract can be calculated by counting spore dilutions on a hemocytometer.…”

Co-ordination between BrlA regulation and secretion of the oxidoreductase FmqD directs selective accumulation of fumiquinazoline C to conidial tissues inAspergillus fumigatus

“…With a few exceptions, localization of these steps in the fungal thallus -whether tissue specificity or cellular localization -is largely unknown. A few studies have shown that certain secondary metabolites localize to specific tissues, such as endocrocin and fumigaclavines to asexual spores (conidia) of the human opportunistic pathogen Aspergillus fumigatus (Coyle et al, 2007;Berthier et al, 2013). The mechanism(s) resulting in placement of metabolites into spores is not known although the study on fumigaclavine synthesis suggests a need for BrlA, the Aspergillus transcription factor required for asexual sporulation (Coyle et al, 2007).…”

Partial Reconstruction of the Ergot Alkaloid Pathway by Heterologous Gene Expression in Aspergillus nidulans

“…Ergot alkaloid synthesis genes are clustered in the A. fumigatus genome [10,11] and are expressed during asexual reproduction [13,14]. Aspergillus nidulans , a model fungus that is closely related to A .…”