Affiliation:
1. Department of Food Microbiology and Toxicology and Food Research Institute
2. Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Madison, Wisconsin 53706
Abstract
ABSTRACT
The opportunistic human pathogen
Aspergillus fumigatus
produces a large quantity of asexual spores (conidia), which are the primary agent causing invasive aspergillosis in immunocompromised patients. We investigated the mechanisms controlling asexual sporulation (conidiation) in
A. fumigatus
via examining functions of four key regulators, GpaA (Gα), AfFlbA (RGS), AfFluG, and AfBrlA, previously studied in
Aspergillus nidulans
. Expression analyses of
gpaA
, Af
flbA
, Af
fluG
, Af
brlA
, and Af
wetA
throughout the life cycle of
A. fumigatus
revealed that, while transcripts of Af
flbA
and Af
fluG
accumulate constantly, the latter two downstream developmental regulators are specifically expressed during conidiation. Both loss-of-function Af
flbA
and dominant activating GpaA
Q204L
mutations resulted in reduced conidiation with increased hyphal proliferation, indicating that GpaA signaling activates vegetative growth while inhibiting conidiation. As GpaA is the primary target of AfFlbA, the dominant interfering GpaA
G203R
mutation suppressed reduced conidiation caused by loss of Af
flbA
function. These results corroborate the hypothesis that functions of G proteins and RGSs are conserved in aspergilli. We then examined functions of the two major developmental activators AfFluG and AfBrlA. While deletion of Af
brlA
eliminated conidiation completely, null mutation of Af
fluG
did not cause severe alterations in
A. fumigatus
sporulation in air-exposed culture, implying that, whereas the two aspergilli may have a common key downstream developmental activator, upstream mechanisms activating
brlA
may be distinct. Finally, both Af
fluG
and Af
flbA
mutants showed reduced conidiation and delayed expression of Af
brlA
in synchronized developmental induction, indicating that these upstream regulators contribute to the proper progression of conidiation.
Publisher
American Society for Microbiology
Subject
Molecular Biology,General Medicine,Microbiology
Cited by
132 articles.
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