Blasticidin A as an Inhibitor of Aflatoxin Production by Aspergillus parasiticus.

Sakuda, Shohei; Ono, Masafumi; Ikeda, Hiroyuki; Nakamura, Takefumi; Inagaki, Yoshio; Kawachi, Ryu; Nakayama, Jiro; Suzuki, Akira; Isogai, Akira; Nagasawa, Hiromichi

doi:10.7164/antibiotics.53.1265

Cited by 34 publications

(22 citation statements)

References 7 publications

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“…3 Blasticidin A (BcA) was found as an antibiotic produced by Streptomyces griseochromogenes, but its structure had not been known. 4,5 We found that BcA strongly inhibited production of both aflatoxin B and G groups by Aspergillus parasiticus, and we determined its structure, 6,7 which is similar to that of aflastatin A, an aflatoxin production inhibitor produced by Streptomyces sp. 8 BcA and aflastatin A reduced the mRNA levels of genes encoding aflatoxin biosynthetic enzymes and a key regulatory protein, AflR.…”

Section: Introductionmentioning

confidence: 96%

Inhibitory activity of blasticidin A, a strong aflatoxin production inhibitor, on protein synthesis of yeast: selective inhibition of aflatoxin production by protein synthesis inhibitors

et al. 2010

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Blasticidin A (BcA), an antibiotic produced by Streptomyces, inhibits aflatoxin production without strong growth inhibition toward aflatoxin-producing fungi. During the course of our study on the mode of action of BcA by two-dimensional differential gel electrophoresis (2D-DIGE), we found a decrease in the abundances of ribosomal proteins in Saccharomyces cerevisiae after exposure to BcA. This phenomenon was also observed by treatment with blasticidin S (BcS) or cycloheximide. BcA inhibited protein synthesis in a galactose-induced expression system in S. cerevisiae similar to BcS and cycloheximide. BcS, but not cycloheximide, inhibited aflatoxin production in Aspergillus parasiticus without inhibition of fungal growth, similar to BcA. A decrease in the abundances of aflatoxin biosynthetic enzymes was observed in 2D-DIGE experiments with Aspergillus flavus after exposure to BcA or BcS. These results suggested that protein synthesis inhibitors are useful to control aflatoxin production.

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Section: Introductionmentioning

confidence: 96%

Inhibitory activity of blasticidin A, a strong aflatoxin production inhibitor, on protein synthesis of yeast: selective inhibition of aflatoxin production by protein synthesis inhibitors

et al. 2010

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“…We also wished to determine the mechanism of aflatoxin production by the fungus at the molecular level. We have found that aflastatins A and B (AsA and AsB), and blasticidin A (BcA), are inhibitors of aflatoxin production, and we have determined their structures; they are produced by Streptomyces, and share a similar structure (Sakuda et al, 1996(Sakuda et al, , 2000aOno et al, 1997Ono et al, , 1998Ikeda et al, 2000). They strongly inhibit aflatoxin production by A. parasiticus by disturbing the primary metabolism of the fungus, which may regulate a pathway leading to expression of aflatoxin biosynthetic enzymes (Kondo et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Dioctatin A is a strong inhibitor of aflatoxin production by Aspergillus parasiticus

et al. 2007

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Dioctatin A (DotA), a metabolite of Streptomyces, is known to be an inhibitor of human dipeptidyl aminopeptidase II. Here, it was found that DotA strongly inhibited aflatoxin production by Aspergillus parasiticus, with an IC 50 value of 4.0 mM. The mycelial growth of the fungus was not affected by the addition of DotA at a concentration of 50 mM, but inhibition of conidiation was observed at the same concentration. DotA inhibited production of norsolorinic acid, an early biosynthetic intermediate of aflatoxin, and it strongly reduced the mRNA levels of genes encoding aflatoxin biosynthetic enzymes, and significantly decreased the mRNA level of aflR, which encodes a key regulatory protein for aflatoxin biosynthesis. In addition to these genes, the mRNA level of brlA, which encodes a conidiation-specific transcription factor, was also reduced by the addition of DotA. It was also found that DotA dramatically enhanced kojic acid production by the fungus. Furthermore, DotA inhibited production of sterigmatocystin, which is a toxic aflatoxin biosynthetic intermediate, and it also inhibited conidiation in Aspergillus nidulans. These results indicate that DotA has pleiotropic effects on regulatory mechanisms of fungal secondary metabolite production and differentiation, leading to inhibition of aflatoxin production.

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“…As three aminoglycosides and phleomycin upregulated AvrLm1, AvrLm4-7 and Lema086540 expression, these results indicate that different types of intracellular stresses activate the transcription of effector-encoding genes in L. maculans. A few studies have already shown that exposure of fungi to aminoglycosides can lead to a deregulation of genes expression, including secondary metabolite gene clusters, but, being mostly analyzed on model, non-pathogenic species, the genes identified did not encompass putative effectors (Gladyshev and Arkhipova, 2011;Sakuda et al, 2000;Yoshinari et al, 2010). It now is of interest to determine if the effect of cycloheximide or phleomycin could be similar in other fungal pathogens and thus be a convenient tool for effector identification and analysis.…”

Section: Discussionmentioning

confidence: 99%

Impact of biotic and abiotic factors on the expression of fungal effector-encoding genes in axenic growth conditions

Meyer

Bourras

Gervais

et al. 2017

Fungal Genetics and Biology

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a b s t r a c tIn phytopathogenic fungi, the expression of hundreds of small secreted protein (SSP)-encoding genes is induced upon primary infection of plants while no or a low level of expression is observed during vegetative growth. In some species such as Leptosphaeria maculans, this coordinated in-planta upregulation of SSP-encoding genes expression relies on an epigenetic control but the signals triggering gene expression in-planta are unknown. In the present study, biotic and abiotic factors that may relieve suppression of SSP-encoding gene expression during axenic growth of L. maculans were investigated. Some abiotic factors (temperature, pH) could have a limited effect on SSP gene expression. In contrast, two types of cellular stresses induced by antibiotics (cycloheximide, phleomycin) activated strongly the transcription of SSP genes. A transcriptomic analysis to cycloheximide exposure revealed that biological processes such as ribosome biosynthesis and rRNA processing were induced whereas important metabolic pathways such as glycogen and nitrogen metabolism, glycolysis and tricarboxylic acid cycle activity were downregulated. A quantitatively different expression of SSP-encoding genes compared to plant infection was also detected. Interestingly, the same physico-chemical parameters as those identified here for L. maculans effectors were identified to regulate positively or negatively the expression of bacterial effectors. This suggests that apoplastic phytopathogens may react to similar physiological parameters for regulation of their effector genes.

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Blasticidin A as an Inhibitor of Aflatoxin Production by Aspergillus parasiticus.

Cited by 34 publications

References 7 publications

Inhibitory activity of blasticidin A, a strong aflatoxin production inhibitor, on protein synthesis of yeast: selective inhibition of aflatoxin production by protein synthesis inhibitors

Inhibitory activity of blasticidin A, a strong aflatoxin production inhibitor, on protein synthesis of yeast: selective inhibition of aflatoxin production by protein synthesis inhibitors

Dioctatin A is a strong inhibitor of aflatoxin production by Aspergillus parasiticus

Impact of biotic and abiotic factors on the expression of fungal effector-encoding genes in axenic growth conditions

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