Characterization of the developmental regulator FlbE in Aspergillus fumigatus and Aspergillus nidulans

Kwon, Nak‐Jung; Shin, Kwang‐Soo; Yu, Jae‐Hyuk

doi:10.1016/j.fgb.2010.08.009

Cited by 68 publications

(67 citation statements)

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“…Moreover, expression of AfuflbC was independent of either AfuflbB or AfuflbE. These results suggest that the proposed model for genetic interactions among upstream developmental regulators in A. nidulans (16,17) is partially applicable for A. fumigatus ( Fig. 8B; see also Discussion).…”

Section: Vol 9 2010mentioning

confidence: 63%

“…Based on the studies of growth and development in the distantly related A. nidulans, we have been dissecting the roles of genes associated with development in A. fumigatus (17,20,40; also Tao and Yu, unpublished). Our previous studies demonstrated that functions of the central regulators BrlA, AbaA, and WetA in conidiogenesis are conserved in A. nidulans and A. fumigatus (20; also Tao and Yu, unpublished).…”

Section: Discussionmentioning

confidence: 99%

“…Our recent studies have demonstrated that A. fumigatus FlbE (AfuFlbE) is crucial for proper conidiation and is functionally conserved in two aspergilli (17). In this study, we characterize AfuflbB and present evidence that FlbB is vital for A. fumigatus morphological development and gliotoxin produc-* Corresponding author.…”

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confidence: 95%

“…Recent studies demonstrated that the bZIP TF FlbB is necessary for the expression of flbD and that FlbB and FlbD activate brlA in a supportive manner (14). The A. nidulans flbE (AniflbE) gene is predicted to encode a 201-amino-acid (aa)-long polypeptide with two conserved yet uncharacterized domains, and it was demonstrated that FlbE and FlbB are functionally interdependent, physically interact in vivo, and colocalize at the hyphal tip in A. nidulans (13).Our recent studies have demonstrated that A. fumigatus FlbE (AfuFlbE) is crucial for proper conidiation and is functionally conserved in two aspergilli (17). In this study, we characterize AfuflbB and present evidence that FlbB is vital for A. fumigatus morphological development and gliotoxin produc-* Corresponding author.…”

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Aspergillus fumigatus flbB Encodes Two Basic Leucine Zipper Domain (bZIP) Proteins Required for Proper Asexual Development and Gliotoxin Production

et al. 2010

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The opportunistic human pathogen Aspergillus fumigatus reproduces asexually by forming a massive number of mitospores called conidia. In this study, we characterize the upstream developmental regulator A. fumigatus flbB (AfuflbB). Northern blotting and cDNA analyses reveal that AfuflbB produces two transcripts predicted to encode two basic leucine zipper domain (bZIP) polypeptides, AfuFlbB␤ (420 amino acids [aa]) and AfuFlbB␣ (390 aa). The deletion of AfuflbB results in delayed/reduced sporulation, precocious cell death, the lack of conidiophore development in liquid submerged culture, altered expression of AfubrlA and AfuabaA, and blocked production of gliotoxin. While introduction of the wild-type (WT) AfuflbB allele fully complemented these defects, disruption of the ATG start codon for either one of the AfuFlbB polypeptides leads to a partial complementation, indicating the need of both polypeptides for WT levels of asexual development and gliotoxin biogenesis. Consistent with this, Aspergillus nidulans flbB ؉ encoding one polypeptide (426 aa) partially complements the AfuflbB null mutation. The presence of 0.6 M KCl in liquid submerged culture suppresses the defects caused by the lack of one, but not both, of the AfuFlbB polypeptides, suggesting a genetic prerequisite for AfuFlbB in A. fumigatus development. Finally, Northern blot analyses reveal that both AfuflbB and AfuflbE are necessary for expression of AfuflbD, suggesting that FlbD functions downstream of FlbB/FlbE in aspergilli.The opportunistic human pathogen Aspergillus fumigatus (reviewed in reference 9) propagates in the environment by producing a massive number of mitotic spores called conidia (19). Under appropriate conditions, the conidium germinates and undergoes vegetative growth that leads to the formation of a network of undifferentiated interconnected hyphae known as the mycelium. After a certain period of hyphal proliferation, in response to appropriate cues (e.g., exposure to air, nutrient deprivation, or osmotic stress) some of the vegetative cells initiate asexual development (conidiation) and go through a series of morphological changes, which result in the formation of conidiophores consisting of foot cell, stalk, vesicle, phialides, and (up to 50,000) conidia (19,26). Conidia (2 to 3 m in diameter) are then released into the environment and are small enough to reach the alveoli after being inhaled by humans (31). In immunocompromised hosts the conidia are able to germinate into invasive hyphae, which penetrate the vasculature and migrate to distal sites (reviewed in reference 26).We have been investigating the mechanisms underlying asexual development and gliotoxin biosynthesis in A. fumigatus, primarily focusing on understanding the functions of a number of developmental regulators identified in the model fungus Aspergillus nidulans (21,30,40). A key step for conidiation in A. nidulans is the activation of brlA encoding a C 2 H 2 zinc finger transcription factor (TF) (1). Together with abaA and wetA, these three elements define a c...

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Section: Vol 9 2010mentioning

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Aspergillus fumigatus flbB Encodes Two Basic Leucine Zipper Domain (bZIP) Proteins Required for Proper Asexual Development and Gliotoxin Production

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“…FlbE is a 201-aa-length polypeptide with two conserved yet uncharacterized domains and colocalizes with FlbB, a basic leucine zipper (b-zip) TF, at the hyphal tip in an actin cytoskeleton-dependent manner (Garzia et al 2009). FlbE physically interacts with FlbB, and they activate FlbD interdependently (Garzia et al 2009;Kwon et al 2010b). FlbD (a cMyb-type TF) and FlbB then cooperatively function in activating expression of brlA (Garzia et al 2010).…”

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NsdD Is a Key Repressor of Asexual Development inAspergillus nidulans

et al. 2014

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Asexual development (conidiation) of the filamentous fungus Aspergillus nidulans occurs via balanced activities of multiple positive and negative regulators. For instance, FluG (+) and SfgA (2) govern upstream regulation of the developmental switch, and BrlA (+) and VosA (2) control the progression and completion of conidiation. To identify negative regulators of conidiation downstream of FluG-SfgA, we carried out multicopy genetic screens using sfgA deletion strains. After visually screening .100,000 colonies, we isolated 61 transformants exhibiting reduced conidiation. Responsible genes were identified as AN3152 (nsdD), AN7507, AN2009, AN1652, AN5833, and AN9141. Importantly, nsdD, a key activator of sexual reproduction, was present in 10 independent transformants. Furthermore, deletion, overexpression, and double-mutant analyses of individual genes have led to the conclusion that, of the six genes, only nsdD functions in the FluG-activated conidiation pathway. The deletion of nsdD bypassed the need for fluG and flbA$flbE, but not brlA or abaA, in conidiation, and partially restored production of the mycotoxin sterigmatocystin (ST) in the DfluG, DflbA, and DflbB mutants, suggesting that NsdD is positioned between FLBs and BrlA in A. nidulans. Nullifying nsdD caused formation of conidiophores in liquid submerged cultures, where wild-type strains do not develop. Moreover, the removal of both nsdD and vosA resulted in even more abundant development of conidiophores in liquid submerged cultures and high-level accumulation of brlA messenger (m)RNA even at 16 hr of vegetative growth. Collectively, NsdD is a key negative regulator of conidiation and likely exerts its repressive role via downregulating brlA.T HE filamentous ascomycete Aspergillus nidulans has served as an excellent model system for studying cell biology, asexual development (conidiation), and secondary metabolism (Timberlake 1990;Martinelli 1994;Yu and Keller 2005). The A. nidulans asexual reproductive cycle can be divided into two distinct phases: growth and development. The growth phase involves germination of an asexually derived spore called a conidium and formation of an undifferentiated network of interconnected hyphal cells that form the mycelium. After a certain vegetative growth period, under appropriate conditions, some of the hyphal cells stop normal growth and begin development by forming complex structures called conidiophores that bear multiple chains of conidia (Adams et al. 1988;Park and Yu 2012a).A key and essential step for conidiophore development in Aspergillus is the activation of brlA, which encodes a C 2 H 2 zinc-finger transcription factor (TF) ( Figure 1A) (Adams et al. 1988;Chang and Timberlake 1993). Further genetic and biochemical studies identified the additional key regulators abaA and wetA that function during the middle and late stages of conidiation, respectively ( Figure 1A) (Sewall et al. 1990;Andrianopoulos and Timberlake 1991;Marshall and Timberlake 1991). These three genes have been proposed to define a c...

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Extracellular proteinase formation in carbon starving Aspergillus nidulans cultures – physiological function and regulation

Szilágyi

Kwon

Bakti

et al. 2011

J. Basic Microbiol.

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Extracellular proteinase formation in carbon depleted cultures of the model filamentous fungus Aspergillus nidulans was studied to elucidate its regulation and possible physiological function. As demonstrated by gene deletion, culture optimization, microbial physiological and enzymological experiments, the PrtA and PepJ proteinases of A. nidulans did not appear to play a decisive role in the autolytic decomposition of fungal cells under the conditions we tested. However, carbon starvation induced formation of the proteinases observable in autolytic cultures. Similar to other degradative enzymes, production of proteinase was regulated by FluG-BrlA asexual developmental signaling and modulated by PacC-dependent pH-responsive signaling. Under the same carbon starved culture conditions, alterations of CreA, MeaB or heterotrimeric G protein mediated signaling pathways caused less significant changes in the formation of extracellular proteinases. Taken together, these results indicate that while the accumulation of PrtA and PepJ is tightly coupled to the initiation of autolysis, they are not essential for autolytic cell wall degradation in A. nidulans. Thus, as Aspergillus genomes contain a large group of genes encoding proteinases with versatile physiological functions, selective control of proteinase production in fungal cells is needed for the improved industrial use of fungi.

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Characterization of the developmental regulator FlbE in Aspergillus fumigatus and Aspergillus nidulans

Cited by 68 publications

References 47 publications

Aspergillus fumigatus flbB Encodes Two Basic Leucine Zipper Domain (bZIP) Proteins Required for Proper Asexual Development and Gliotoxin Production

Aspergillus fumigatus flbB Encodes Two Basic Leucine Zipper Domain (bZIP) Proteins Required for Proper Asexual Development and Gliotoxin Production

NsdD Is a Key Repressor of Asexual Development inAspergillus nidulans

Extracellular proteinase formation in carbon starving Aspergillus nidulans cultures – physiological function and regulation

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