Inhibition of ergosterol biosynthesis is not accompanied by a change in fatty acid composition in Saccharomyces cerevisiae treated with the antifungal agent 6-amino-2-n-pentylthiobenzothiazole

Kuchta, T.; Léka, C; Kubinec, Róbert; Russell, Nicholas J.

doi:10.1111/j.1574-6968.1997.tb10347.x

Cited by 3 publications

(2 citation statements)

References 7 publications

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“…APB has been shown to bind to Erg25p and inhibits its catalytic function in a competitive manner (9,21). The treatment of yeast with APB inhibited the biosynthesis of ergosterol and led to the accumulation of the methylated sterol precursors, such as ergosta-5,7-dienol and squalene, but had no significant effect on the composition and the rate of biosynthesis of fatty acids (22). We found that applying increasing amounts of APB to the growth medium affected both yeast growth and TBSV accumulation ( Fig.…”

Section: Downregulation Of Erg25 Mrna Level In Yeast Reduces Tbsv Rnamentioning

confidence: 99%

Inhibition of Sterol Biosynthesis Reduces Tombusvirus Replication in Yeast and Plants

Sharma

Sasvari

Nagy

2010

J Virol

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The replication of plus-strand RNA viruses depends on subcellular membranes. Recent genome-wide screens have revealed that the sterol biosynthesis genes ERG25 and ERG4 affected the replication of Tomato bushy stunt virus (TBSV) in a yeast model host. To further our understanding of the role of sterols in TBSV replication, we demonstrate that the downregulation of ERG25 or the inhibition of the activity of Erg25p with an inhibitor (6-amino-2-n-pentylthiobenzothiazole; APB) leads to a 3-to 5-fold reduction in TBSV replication in yeast. In addition, the sterol biosynthesis inhibitor lovastatin reduced TBSV replication by 4-fold, confirming the importance of sterols in viral replication. We also show reduced stability for the p92 pol viral replication protein as well as a decrease in the in vitro activity of the tombusvirus replicase when isolated from APB-treated yeast. Moreover, APB treatment inhibits TBSV RNA accumulation in plant protoplasts and in Nicotiana benthamiana leaves. The inhibitory effect of APB on TBSV replication can be complemented by exogenous stigmasterol, the main plant sterol, suggesting that sterols are required for TBSV replication. The silencing of SMO1 and SMO2 genes, which are orthologs of ERG25, in N. benthamiana reduced TBSV RNA accumulation but had a lesser inhibitory effect on the unrelated Tobacco mosaic virus, suggesting that various viruses show different levels of dependence on sterol biosynthesis for their replication.Plus-stranded RNA [(ϩ)RNA] viruses usurp various intracellular/organellar membranes for their replication. These cellular membranes are thought to facilitate the building of viral factories, promote a high concentration of membrane-bound viral proteins, and provide protection against cellular nucleases and proteases (1,12,35,44). The membrane lipids and proteins may serve as scaffolds for targeting the viral replication proteins or for the assembly of the viral replicase complex. The subcellular membrane also may provide critical lipid or protein cofactors to activate/modulate the function of the viral replicase. Indeed, the formation of spherules, consisting of lipid membranes bended inward and viral replication proteins as well as recruited host proteins, has been demonstrated for several (ϩ)RNA viruses (20,30,48). These virus-induced spherules serve as sites of viral replication. Importantly, (ϩ)RNA viruses also induce membrane proliferation that requires new lipid biosynthesis. Therefore, it is not surprising that several genome-wide screens for the identification of host factors affecting (ϩ)RNA virus replication unraveled lipid biosynthesis/metabolism genes (8,23,38,50). However, in spite of these intensive efforts, understanding the roles of various lipids and lipid biosynthesis enzymes and pathways in (ϩ)RNA virus replication is limited.Tomato bushy stunt virus (TBSV) is among the most advanced model systems regarding the identification of host factors affecting (ϩ)RNA virus replication (32). Among the five proteins encoded by the TBSV genome, only the p33 re...

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Section: Downregulation Of Erg25 Mrna Level In Yeast Reduces Tbsv Rnamentioning

confidence: 99%

Inhibition of Sterol Biosynthesis Reduces Tombusvirus Replication in Yeast and Plants

Sharma

Sasvari

Nagy

2010

J Virol

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“…41) did not efficiently comply with the criteria of interesting new drug targets [25][26][27][28]. Recently, the characterization of a natural steroidal inhibitor of a sterol-4α-carboxylate-3-dehydrogenase, an enzyme of the sterol-C4-demethylation complex from yeast (C4DMC) clearly indicated that many target enzymes had been overlooked so far in chemical and pharmaceutical screenings for new bioactive ligands [29,30].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Phytosterol Biosynthesis by Azasterols

et al. 2020

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Inhibitors of enzymes in essential cellular pathways are potent probes to decipher intricate physiological functions of biomolecules. The analysis of Arabidopsis thaliana sterol profiles upon treatment with a series of azasterols reveals a specific in vivo inhibition of SMT2, a plant sterol-C-methyltransferase acting as a branch point between the campesterol and sitosterol biosynthetic segments in the pathway. Side chain azasteroids that modify sitosterol homeostasis help to refine its particular function in plant development.

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Identification of Cryptococcus neoformans Temperature-Regulated Genes with a Genomic-DNA Microarray

Kraus¹,

Boily²,

Giles³

et al. 2004

Eukaryot Cell

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The ability to survive and proliferate at 37°C is an essential virulence attribute of pathogenic microorganisms. A partial-genome microarray was used to profile gene expression in the human-pathogenic fungus Cryptococcus neoformans during growth at 37°C. Genes with orthologs involved in stress responses were induced during growth at 37°C, suggesting that a conserved transcriptional program is used by C. neoformans to alter gene expression during stressful conditions. A gene encoding the transcription factor homolog Mga2 was induced at 37°C and found to be important for high-temperature growth. Genes encoding fatty acid biosynthetic enzymes were identified as potential targets of Mga2, suggesting that membrane remodeling is an important component of adaptation to high growth temperatures. mga2⌬ mutants were extremely sensitive to the ergosterol synthesis inhibitor fluconazole, indicating a coordination of the synthesis of membrane component precursors. Unexpectedly, genes involved in amino acid and pyrimidine biosynthesis were repressed at 37°C, but components of these pathways were found to be required for high-temperature growth. Our findings demonstrate the utility of even partial-genome microarrays for delineating regulatory cascades that contribute to microbial pathogenesis.

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Inhibition of ergosterol biosynthesis is not accompanied by a change in fatty acid composition in Saccharomyces cerevisiae treated with the antifungal agent 6-amino-2-n-pentylthiobenzothiazole

Cited by 3 publications

References 7 publications

Inhibition of Sterol Biosynthesis Reduces Tombusvirus Replication in Yeast and Plants

Inhibition of Sterol Biosynthesis Reduces Tombusvirus Replication in Yeast and Plants

Inhibition of Phytosterol Biosynthesis by Azasterols

Identification of Cryptococcus neoformans Temperature-Regulated Genes with a Genomic-DNA Microarray

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