G Protein α Subunit GpaB is Required for Asexual Development, Aflatoxin Biosynthesis and Pathogenicity by Regulating cAMP Signaling in Aspergillus flavus

Liu, Yinghang; Yang, Ke; Qin, Qiuping; Lin, Guinan; Hu, Tianran; Xu, Zhangling; Wang, Shihua

doi:10.3390/toxins10030117

Cited by 26 publications

(24 citation statements)

References 39 publications

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“…Unlike our results, the phenotype of the ∆gpaB mutant in A. flavus is slightly different. The colony size of the ∆gpaB mutant was increased compared to that of WT and complemented strains [12], suggesting that the roles of GpaB may not be conserved in Aspergillus.…”

Section: Discussionmentioning

confidence: 96%

“…In A. nidulans, the G protein mediates cAMP signaling are required for sterigmatocystin biosynthesis [11]. In A. flavus, The Gα subunit GpaB is also essential for the biosynthesis of aflatoxins, and aflatoxin production was drastically inhibited by the loss gpaB [12]. Despite the small difference in the amounts, the Gα encoding gene deletion mutants of A. fumigatus produced less GT than the WT strain.…”

Section: Discussionmentioning

confidence: 99%

“…The activity of GanB-mediated signaling is negatively regulated by RgsA [11]. The GanB homologue of A. flavus GpaB function in conidiation, stress responses, toxin production, and virulence [12]. The function of GanA in A. nidulans is not yet characterized.…”

Section: Introductionmentioning

confidence: 99%

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Comparative Characterization of G Protein α Subunits in Aspergillus fumigatus

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Comparative Characterization of G Protein α Subunits in Aspergillus fumigatus

et al. 2020

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“…In eukaryotes, it has been reported that cAMP activates the protein kinase A (PKA) pathway by binding to the regulatory subunit (PkaR) that leads to its dissociation from the catalytic subunit (PkaC), which activates several transcription factors that control the final morphological fate of the cell (Choi, Jung, & Kronstad, 2015). The fungal PKA pathway is involved in several functions, including asexual sporulation, nutrient sensing, growth and virulence (Demuyser, Van Genechten, Mizuno, Colombo, & Van Dijck, 2018;Fuller & Rhodes, 2012;Kozubowski, Lee, & Heitman, 2009;Liu et al, 2018).…”

Section: The Addition Of Camp To Cultures Of Diverse Dimorphic Speciementioning

confidence: 99%

The heterotrimeric G‐protein beta subunit Gpb1 controls hyphal growth under low oxygen conditions through the protein kinase A pathway and is essential for virulence in the fungusMucor circinelloides

Valle-Maldonado

Patiño-Medina

Pérez-Arques

et al. 2020

Cellular Microbiology

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Mucor circinelloides, a dimorphic opportunistic pathogen, expresses three heterotrimeric G‐protein beta subunits (Gpb1, Gpb2 and Gpb3). The Gpb1‐encoding gene is up‐regulated during mycelial growth compared with that in the spore or yeast stage. gpb1 deletion mutation analysis revealed its relevance for an adequate development during the dimorphic transition and for hyphal growth under low oxygen concentrations. Infection assays in mice indicated a phenotype with considerably reduced virulence and tissue invasiveness in the deletion mutants (Δgpb1) and decreased host inflammatory response. This finding could be attributed to the reduced filamentous growth in animal tissues compared with that of the wild‐type strain. Mutation in a regulatory subunit of cAMP‐dependent protein kinase A (PKA) subunit (PkaR1) resulted in similar phenotypes to Δgpb1. The defects exhibited by the Δgpb1 strain were genetically suppressed by pkaR1 overexpression, indicating that the PKA pathway is controlled by Gpb1 in M. circinelloides. Moreover, during growth under low oxygen levels, cAMP levels were much higher in the Δgpb1 than in the wild‐type strain, but similar to those in the ΔpkaR1 strain. These findings reveal that M. circinelloides possesses a signal transduction pathway through which the Gpb1 heterotrimeric G subunit and PkaR1 control mycelial growth in response to low oxygen levels.

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“…The biosynthesis of these SMs cannot only be controlled by the intra-cluster regulating genes but can also be adjusted by the off-cluster global regulating genes, such as Lae A, Ve A, and related genes in the G-protein signaling pathway (GPSP) (Fox and Howlett, 2008; Liu Q. et al, 2016; Lin et al, 2018). GPSPs, including the G-protein coupled receptor (GPCR), heterotrimeric G-protein (G-protein) and downstream effectors (Seo and Yu, 2006), play vital roles in growth, differentiation, SMs biosynthesis, pathogenicity and toxicity in filamentous fungi (Yu et al, 2008; Corrochano et al, 2016; Moretti et al, 2017; Liu et al, 2018; van den Hoogen et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Effects of Different G-Protein α-Subunits on Growth, Development and Secondary Metabolism of Monascus ruber M7

et al. 2019

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Strains of Monascus filamentous fungal species have been used to produce fermented foods in Asian countries, such as China, Japan, and The Korean Peninsula, for nearly 2,000 years. At present, their fermented products are widely used as food additives and nutraceutical supplements worldwide owing to their production of beneficial secondary metabolites. Heterotrimeric G-protein signaling pathways participate in regulating multiple biological processes in fungi. Previously, we identified three Monascus ruber M7 G-protein α subunits (Mga1–3) and demonstrated that Mga1 can regulate growth, reproduction and some secondary metabolites’ production. Here, we systematically analyzed and compared the roles of mga 1–3 by combining single- and double-gene(s) knockouts and their transcriptomic data. First, mga 2 and mga 3 knock-out mutants and pairwise combinations of mga 1–3 deletion strains were generated. Then the changes in growth, development and the main secondary metabolites, Monascus pigments and citrinin, in these mutants were systematically compared with M. ruber M7. Moreover, RNA-Seq analyses of these mutants were performed. All three Gα subunits worked together to regulate biological processes in M. ruber M7, with Mga1 playing a major role, while Mga2 and Mga3 playing supplemental roles. According to the existing literatures which we can find, gene knock-out mutants of the pairwise combination of mga 1–3 and their transcriptome analysis are first reported in this study. The current results have clearly demonstrated the functional division of Mga1–3 in M. ruber M7, and could provide a deeper understanding of the effects of different Gα subunits on growth, development and secondary metabolism in other filamentous fungi.

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G Protein α Subunit GpaB is Required for Asexual Development, Aflatoxin Biosynthesis and Pathogenicity by Regulating cAMP Signaling in Aspergillus flavus

Cited by 26 publications

References 39 publications

Comparative Characterization of G Protein α Subunits in Aspergillus fumigatus

Comparative Characterization of G Protein α Subunits in Aspergillus fumigatus

The heterotrimeric G‐protein beta subunit Gpb1 controls hyphal growth under low oxygen conditions through the protein kinase A pathway and is essential for virulence in the fungusMucor circinelloides

Effects of Different G-Protein α-Subunits on Growth, Development and Secondary Metabolism of Monascus ruber M7

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