EP007 Analysis of interactions of macrophages with the opportunistic human pathogen Aspergillus fumigatus

Opportunistic pathogens like Aspergillus fumigatus have strategies to protect themselves against reactive oxygen species like hydrogen peroxides and superoxides that are produced by immune cells. DHN-melanin is the green pigment on conidia of Aspergillus fumigatus and more than 2 decades ago was reported to protect conidia against hydrogen peroxide.

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The Siderophore Transporters Sit1 and Sit2 Are Essential for Utilization of Ferrichrome-, Ferrioxamine- and Coprogen-Type Siderophores in Aspergillus fumigatus

Journal of Fungi ◽

10.3390/jof7090768 ◽

2021 ◽

Vol 7 (9) ◽

pp. 768

Author(s):

Mario Aguiar ◽

Thomas Orasch ◽

Matthias Misslinger ◽

Anna-Maria Dietl ◽

Fabio Gsaller ◽

...

Keyword(s):

Aspergillus Fumigatus ◽

Filamentous Fungi ◽

Fungal Pathogens ◽

Fungal Infections ◽

The Novel ◽

Human Pathogen ◽

Substrate Specificities ◽

Triacetylfusarinine C ◽

Opportunistic Human Pathogen ◽

Siderophore Transporter

Siderophore-mediated acquisition of iron has been shown to be indispensable for the virulence of several fungal pathogens, the siderophore transporter Sit1 was found to mediate uptake of the novel antifungal drug VL-2397, and siderophores were shown to be useful as biomarkers as well as for imaging of fungal infections. However, siderophore uptake in filamentous fungi is poorly characterized. The opportunistic human pathogen Aspergillus fumigatus possesses five putative siderophore transporters. Here, we demonstrate that the siderophore transporters Sit1 and Sit2 have overlapping, as well as unique, substrate specificities. With respect to ferrichrome-type siderophores, the utilization of ferrirhodin and ferrirubin depended exclusively on Sit2, use of ferrichrome A depended mainly on Sit1, and utilization of ferrichrome, ferricrocin, and ferrichrysin was mediated by both transporters. Moreover, both Sit1 and Sit2 mediated use of the coprogen-type siderophores coprogen and coprogen B, while only Sit1 transported the bacterial ferrioxamine-type xenosiderophores ferrioxamines B, G, and E. Neither Sit1 nor Sit2 were important for the utilization of the endogenous siderophores fusarinine C and triacetylfusarinine C. Furthermore, A. fumigatus was found to lack utilization of the xenosiderophores schizokinen, basidiochrome, rhizoferrin, ornibactin, rhodotorulic acid, and enterobactin. Taken together, this study characterized siderophore use by A. fumigatus and substrate characteristics of Sit1 and Sit2.

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Upstream and Downstream Regulation of Asexual Development in Aspergillus fumigatus

Eukaryotic Cell ◽

10.1128/ec.00192-06 ◽

2006 ◽

Vol 5 (10) ◽

pp. 1585-1595 ◽

Cited By ~ 104

Author(s):

Jae-Hyung Mah ◽

Jae-Hyuk Yu

Keyword(s):

Aspergillus Fumigatus ◽

G Proteins ◽

Asexual Development ◽

Human Pathogen ◽

Loss Of Function ◽

Primary Target ◽

Asexual Sporulation ◽

Opportunistic Human Pathogen ◽

Upstream Regulators ◽

Primary Agent

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, AfflbA, AffluG, AfbrlA, and AfwetA throughout the life cycle of A. fumigatus revealed that, while transcripts of AfflbA and AffluG accumulate constantly, the latter two downstream developmental regulators are specifically expressed during conidiation. Both loss-of-function AfflbA and dominant activating GpaAQ204L 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 GpaAG203R mutation suppressed reduced conidiation caused by loss of AfflbA 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 AfbrlA eliminated conidiation completely, null mutation of AffluG 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 AffluG and AfflbA mutants showed reduced conidiation and delayed expression of AfbrlA in synchronized developmental induction, indicating that these upstream regulators contribute to the proper progression of conidiation.

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Faculty Opinions recommendation of The mtfA transcription factor gene controls morphogenesis, gliotoxin production, and virulence in the opportunistic human pathogen Aspergillus fumigatus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718349325.793495654 ◽

2014 ◽

Author(s):

Margaret Katz

Keyword(s):

Transcription Factor ◽

Aspergillus Fumigatus ◽

Human Pathogen ◽

Transcription Factor Gene ◽

Factor Gene ◽

Opportunistic Human Pathogen

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Genome Sequences of Two Strains of the Food Spoilage Mold Aspergillus fischeri

Microbiology Resource Announcements ◽

10.1128/mra.01328-19 ◽

2019 ◽

Vol 8 (50) ◽

Cited By ~ 1

Author(s):

Shu Zhao ◽

Jean-Paul Latgé ◽

John G. Gibbons

Keyword(s):

Comparative Genomics ◽

Aspergillus Fumigatus ◽

Close Relative ◽

Food Spoilage ◽

Human Pathogen ◽

Genome Sequences ◽

Content Type ◽

Aspergillus Fischeri ◽

Common Food ◽

Opportunistic Human Pathogen

Aspergillus fischeri is a common food spoilage fungus and a close relative of the opportunistic human pathogen Aspergillus fumigatus. Here, we sequenced the genomes of two isolates of A. fischeri to build resources for comparative genomics and to aid in differentiation between A. fischeri subspecies.

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Copper Utilization, Regulation, and Acquisition by Aspergillus fumigatus

International Journal of Molecular Sciences ◽

10.3390/ijms20081980 ◽

2019 ◽

Vol 20 (8) ◽

pp. 1980 ◽

Cited By ~ 9

Author(s):

Nicholas Raffa ◽

Nir Osherov ◽

Nancy P. Keller

Keyword(s):

Aspergillus Fumigatus ◽

Small Molecules ◽

Copper Homeostasis ◽

Human Pathogen ◽

Nitrogen Acquisition ◽

Microbial Toxin ◽

Copper Chelators ◽

Copper Availability ◽

Opportunistic Human Pathogen ◽

Dependent Processes

Copper is an essential micronutrient for the opportunistic human pathogen, Aspergillus fumigatus. Maintaining copper homeostasis is critical for survival and pathogenesis. Copper-responsive transcription factors, AceA and MacA, coordinate a complex network responsible for responding to copper in the environment and determining which response is necessary to maintain homeostasis. For example, A. fumigatus uses copper exporters to mitigate the toxic effects of copper while simultaneously encoding copper importers and small molecules to ensure proper supply of the metal for copper-dependent processes such a nitrogen acquisition and respiration. Small molecules called isocyanides recently found to be produced by A. fumigatus may bind copper and partake in copper homeostasis similarly to isocyanide copper chelators in bacteria. Considering that the host uses copper as a microbial toxin and copper availability fluctuates in various environmental niches, understanding how A. fumigatus maintains copper homeostasis will give insights into mechanisms that facilitate the development of invasive aspergillosis and its survival in nature.

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