Insights to fungal biology through LaeA sleuthing

Jain, Sachin; Keller, Nancy P.

doi:10.1016/j.fbr.2013.05.004

Cited by 53 publications

(45 citation statements)

References 92 publications

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“…The LaeA protein is a methyltransferase (83) conserved throughout ascomycete fungi and is known for its role in global regulation of fungal secondary metabolism (29,84). However, additional evidence is surfacing linking LaeA-mediated regulation of primary metabolic processes as well, such as iron (85) and sulfur (S. Jain and N. P. Keller, unpublished data) metabolism.…”

Section: Discussionmentioning

confidence: 99%

Distinct Innate Immune Phagocyte Responses to Aspergillus fumigatus Conidia and Hyphae in Zebrafish Larvae

et al. 2014

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f Aspergillus fumigatus is the most common filamentous fungal pathogen of immunocompromised hosts, resulting in invasive aspergillosis (IA) and high mortality rates. Innate immunity is known to be the predominant host defense against A. fumigatus; however, innate phagocyte responses to A. fumigatus in an intact host and their contributions to host survival remain unclear. Here, we describe a larval zebrafish A. fumigatus infection model amenable to real-time imaging of host-fungal interactions in live animals. Following infection with A. fumigatus, innate phagocyte populations exhibit clear preferences for different fungal morphologies: macrophages rapidly phagocytose conidia and form aggregates around hyphae, while the neutrophil response is dependent upon the presence of hyphae. Depletion of macrophages rendered host larvae susceptible to invasive disease. Moreover, a zebrafish model of human leukocyte adhesion deficiency with impaired neutrophil function also resulted in invasive disease and impaired host survival. In contrast, macrophage-deficient but not neutrophil-deficient larvae exhibited attenuated disease following challenge with a less virulent (⌬laeA) strain of A. fumigatus, which has defects in secondary metabolite production. Taking these results together, we have established a new vertebrate model for studying innate immune responses to A. fumigatus that reveals distinct roles for neutrophils and macrophages in mediating host defense against IA.

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Section: Discussionmentioning

confidence: 99%

Distinct Innate Immune Phagocyte Responses to Aspergillus fumigatus Conidia and Hyphae in Zebrafish Larvae

et al. 2014

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“…The availability of genomes, coupled to in silico bioinformatic predictions and in some cases further facilitated by metabolomics studies, has led to the discovery of an increasing number of compounds in a wide range of fungi (28). Additional strategies have included removal (via gene knockout) of repressors, epigenetic manipulation, characterization of "global regulators" of secondary metabolite production (e.g., LaeA), and screening for secondary metabolite hyperproducers (27,29,30).…”

Section: Discussionmentioning

confidence: 99%

Regulatory cascade and biological activity of Beauveria bassiana oosporein that limits bacterial growth after host death

Fan

Liu

Keyhani

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

124

119

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The regulatory network and biological functions of the fungal secondary metabolite oosporein have remained obscure. Beauveria bassiana has evolved the ability to parasitize insects and outcompete microbial challengers for assimilation of host nutrients. A novel zinc finger transcription factor, BbSmr1 (B. bassiana secondary metabolite regulator 1), was identified in a screen for oosporein overproduction. Deletion of Bbsmr1 resulted in up-regulation of the oosporein biosynthetic gene cluster (OpS genes) and constitutive oosporein production. Oosporein production was abolished in double mutants of Bbsmr1 and a second transcription factor, OpS3, within the oosporein gene cluster (ΔBbsmr1ΔOpS3), indicating that BbSmr1 acts as a negative regulator of OpS3 expression. Real-time quantitative PCR and a GFP promoter fusion construct of OpS1, the oosporein polyketide synthase, indicated that OpS1 is expressed mainly in insect cadavers at 24-48 h after death. Bacterial colony analysis in B. bassiana-infected insect hosts revealed increasing counts until host death, with a dramatic decrease (∼90%) after death that correlated with oosporein production. In vitro studies verified the inhibitory activity of oosporein against bacteria derived from insect cadavers. These results suggest that oosporein acts as an antimicrobial compound to limit microbial competition on B. bassiana-killed hosts, allowing the fungus to maximally use host nutrients to grow and sporulate on infected cadavers.Beauveria bassiana | oosporein | biological role | transcription factor | fungal-bacterial competition

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“…In 2008, it was shown that LaeA reacts with VeA and VelB in the Velvet complex, which has a global regulatory effect on secondary metabolism [3]. In filamentous ascomycetes, the Velvet complex and its regulatory effect are conserved [18]. Since its first description in 2004, several hundred articles refer to LaeA [18].…”

Section: Introductionmentioning

confidence: 98%

The global regulator LaeA controls production of citric acid and endoglucanases inAspergillus carbonarius

Linde

Zoglowek

Lübeck

et al. 2016

Journal of Industrial Microbiology and Biotechnology

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The global regulatory protein LaeA is known for regulating the production of many kinds of secondary metabolites in Aspergillus species, as well as sexual and asexual reproduction, and morphology. In Aspergillus carbonarius, it has been shown that LaeA regulates production of ochratoxin. We have investigated the regulatory effect of LaeA on production of citric acid and cellulolytic enzymes in A. carbonarius. Two types of A. carbonarius strains, having laeA knocked out or overexpressed, were constructed and tested in fermentation. The knockout of laeA significantly decreased the production of citric acid and endoglucanases, but did not reduce the production of beta-glucosidases or xylanases. The citric acid accumulation was reduced with 74-96 % compared to the wild type. The endoglucanase activity was reduced with 51-78 %. Overexpression of LaeA seemed not to have an effect on citric acid production or on cellulose or xylanase activity.

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Insights to fungal biology through LaeA sleuthing

Cited by 53 publications

References 92 publications

Distinct Innate Immune Phagocyte Responses to Aspergillus fumigatus Conidia and Hyphae in Zebrafish Larvae

Distinct Innate Immune Phagocyte Responses to Aspergillus fumigatus Conidia and Hyphae in Zebrafish Larvae

Regulatory cascade and biological activity of Beauveria bassiana oosporein that limits bacterial growth after host death

The global regulator LaeA controls production of citric acid and endoglucanases inAspergillus carbonarius

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