scholarly journals Upstream and Downstream Regulation of Asexual Development in Aspergillus fumigatus

2006 ◽  
Vol 5 (10) ◽  
pp. 1585-1595 ◽  
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.

scholarly journals The Protective Role of 1,8-Dihydroxynaphthalene–Melanin on Conidia of the Opportunistic Human Pathogen Aspergillus fumigatus Revisited: No Role in Protection against Hydrogen Peroxide and Superoxides

mSphere ◽  
2022 ◽  
Author(s):  
E. M. Keizer ◽  
I. D. Valdes ◽  
B. L. McCann ◽  
E. M. Bignell ◽  
H. A. B. Wösten ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Aspergillus Fumigatus ◽  
Protective Role ◽  
Oxygen Species ◽  
Human Pathogen ◽  
Opportunistic Pathogens ◽  
Green Pigment ◽  
Content Type ◽  
Opportunistic Human Pathogen

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.

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

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.

scholarly journals Comparative Characterization of G Protein α Subunits in Aspergillus fumigatus

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 272 ◽  
Author(s):  
Yong-Ho Choi ◽  
Na-Young Lee ◽  
Sung-Su Kim ◽  
Hee-Soo Park ◽  
Kwang-Soo Shin
Keyword(s):  
Protein Kinase ◽  
Aspergillus Fumigatus ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
G Protein ◽  
G Proteins ◽  
Asexual Development ◽  
Pkc Signaling ◽  
Α Subunits ◽  
G Protein Α Subunits

Trimeric G proteins play a central role in the G protein signaling in filamentous fungi and Gα subunits are the major component of trimeric G proteins. In this study, we characterize three Gα subunits in the human pathogen Aspergillus fumigatus. While the deletion of gpaB and ganA led to reduced colony growth, the growth of the ΔgpaA strain was increased in minimal media. The germination rate, conidiation, and mRNA expression of key asexual development regulators were significantly decreased by the loss of gpaB. In contrast, the deletion of gpaA resulted in increased conidiation and mRNA expression levels of key asexual regulators. The deletion of gpaB caused a reduction in conidial tolerance against H2O2, but not in paraquat (PQ). Moreover, the ΔgpaB mutant showed enhanced susceptibility against membrane targeting azole antifungal drugs and reduced production of gliotoxin (GT). The protein kinase A (PKA) activity of the ΔganA strain was severely decreased and protein kinase C (PKC) activity was detected all strains at similar levels, indicating that all G protein α subunits of A. fumigatus may be a component of the cAMP/PKA signaling pathway and appear to possess the PKC signaling pathway as an alternative backup pathway to compensate for PKA depletion. Collectively, the three Gα subunits regulate growth, germination, asexual development, resistance to oxidative stress, and GT production differently via the PKA or PKC signaling pathway. The function of GanA of A. fumigatus was elucidated for the first time.

scholarly journals An LaeA- and BrlA-Dependent Cellular Network Governs Tissue-Specific Secondary Metabolism in the Human PathogenAspergillus fumigatus

mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Abigail L. Lind ◽  
Fang Yun Lim ◽  
Alexandra A. Soukup ◽  
Nancy P. Keller ◽  
Antonis Rokas
Keyword(s):  
Aspergillus Fumigatus ◽  
Secondary Metabolism ◽  
Filamentous Fungi ◽  
Vegetative Growth ◽  
Cellular Network ◽  
Asexual Development ◽  
Human Pathogen ◽  
Wild Type ◽  
Cellular Processes ◽  
Type Strains

ABSTRACTBiosynthesis of many ecologically important secondary metabolites (SMs) in filamentous fungi is controlled by several global transcriptional regulators, like the chromatin modifier LaeA, and tied to both development and vegetative growth. InAspergillusmolds, asexual development is regulated by the BrlA > AbaA > WetA transcriptional cascade. To elucidate BrlA pathway involvement in SM regulation, we examined the transcriptional and metabolic profiles of ΔbrlA, ΔabaA, and ΔwetAmutant and wild-type strains of the human pathogenAspergillus fumigatus. We find that BrlA, in addition to regulating production of developmental SMs, regulates vegetative SMs and the SrbA-regulated hypoxia stress response in a concordant fashion to LaeA. We further show that the transcriptional and metabolic equivalence of the ΔbrlAand ΔlaeAmutations is mediated by an LaeA requirement preventing heterochromatic marks in thebrlApromoter. These results provide a framework for the cellular network regulating not only fungal SMs but diverse cellular processes linked to virulence of this pathogen.IMPORTANCEFilamentous fungi produce a spectacular variety of small molecules, commonly known as secondary or specialized metabolites (SMs), which are critical to their ecologies and lifestyles (e.g., penicillin, cyclosporine, and aflatoxin). Elucidation of the regulatory network that governs SM production is a major question of both fundamental and applied research relevance. To shed light on the relationship between regulation of development and regulation of secondary metabolism in filamentous fungi, we performed global transcriptomic and metabolomic analyses on mutant and wild-type strains of the human pathogenAspergillus fumigatusunder conditions previously shown to induce the production of both vegetative growth-specific and asexual development-specific SMs. We find that the genebrlA, previously known as a master regulator of asexual development, is also a master regulator of secondary metabolism and other cellular processes. We further show thatbrlAregulation of SM is mediated bylaeA, one of the master regulators of SM, providing a framework for the cellular network regulating not only fungal SMs but diverse cellular processes linked to virulence of this pathogen.

scholarly journals A LaeA- and BrlA-dependent cellular network governs tissue-specific secondary metabolism in the human pathogen Aspergillus fumigatus

2017 ◽  
Author(s):  
Abigail L. Lind ◽  
Fang Yun Lim ◽  
Alexandra A. Soukup ◽  
Nancy P. Keller ◽  
Antonis Rokas
Keyword(s):  
Secondary Metabolites ◽  
Aspergillus Fumigatus ◽  
Cellular Network ◽  
Transcriptional Regulators ◽  
Asexual Development ◽  
Metabolic Profiles ◽  
Human Pathogen ◽  
Wild Type ◽  
Cellular Processes ◽  
Type Strains

AbstractBiosynthesis of many ecologically important secondary metabolites (SMs) in filamentous fungi is controlled by several global transcriptional regulators, like the chromatin modifier LaeA, and tied to both development and vegetative growth. In Aspergillus molds, asexual development is regulated by the BrlA>AbaA>WetA transcriptional cascade. To elucidate BrlA pathway involvement in SM regulation, we examined the transcriptional and metabolic profiles of ΔbrlA, ΔabaA, ΔwetA and wild-type strains of the human pathogen Aspergillus fumigatus. We find that BrlA, in addition to regulating production of developmental SMs, regulates vegetative SMs and the SrbA-regulated hypoxia stress response in a concordant fashion to LaeA. We further show that the transcriptional and metabolic equivalence of ΔbrlA and ΔlaeA is mediated by a LaeA requirement preventing heterochromatic marks in the brlA promoter. These results provide a framework for the cellular network regulating not only fungal SMs but diverse cellular processes linked to virulence of this pathogen.

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

2019 ◽  
Vol 8 (50) ◽  
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.

scholarly journals Copper Utilization, Regulation, and Acquisition by Aspergillus fumigatus

2019 ◽  
Vol 20 (8) ◽  
pp. 1980 ◽  
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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