Metal ions modulate gene expression and accumulation of the mycotoxins aflatoxin and zearalenone

Cuero, R. G.; Ouellet, Thérèse

doi:10.1111/j.1365-2672.2004.02492.x

Cited by 33 publications

(29 citation statements)

References 21 publications

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“…It is was previously reported that divalent cations have an influence on the production of mycotoxins/secondary metabolites in several ascomycetes, including members of the Aspergillus genus (25). When adding iron, we observed the same with respect to sesquiterpenes.…”

Section: Figsupporting

confidence: 72%

The Volatome of Aspergillus fumigatus

2014

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bEarly detection of invasive aspergillosis is absolutely required for efficient therapy of this fungal infection. The identification of fungal volatiles in patient breath can be an alternative for the detection of Aspergillus fumigatus that still remains problematic. In this work, we investigated the production of volatile organic compounds (VOCs) by A. fumigatus in vitro, and we show that volatile production depends on the nutritional environment. A. fumigatus produces a multiplicity of VOCs, predominantly terpenes and related compounds. The production of sesquiterpenoid compounds was found to be strongly induced by increased iron concentrations and certain drugs, i.e., pravastatin. Terpenes that were always detectable in large amounts were ␣-pinene, camphene, and limonene, as well as sesquiterpenes, identified as ␣-bergamotene and ␤-trans-bergamotene. Other substance classes that were found to be present in the volatome, such as 1-octen-3-ol, 3-octanone, and pyrazines, were found only under specific growth conditions. Drugs that interfere with the terpene biosynthesis pathway influenced the composition of the fungal volatome, and most notably, a block of sesquiterpene biosynthesis by the bisphosphonate alendronate fundamentally changed the VOC composition. Using deletion mutants, we also show that a terpene cyclase and a putative kaurene synthase are essential for the synthesis of volatile terpenes by A. fumigatus. The present analysis of in vitro volatile production by A. fumigatus suggests that VOCs may be used in the diagnosis of infections caused by this fungus.A spergillus fumigatus is an opportunistic fungal pathogen that causes life-threatening invasive pulmonary infections (invasive aspergillosis [IA]) among immunocompromised patients. A sensitive, rapid, and accurate diagnostic assay for invasive aspergillosis is required to successfully fight this fungal infection (1). It has recently been proposed that the detection of volatiles can be used for the diagnosis of pulmonary infections (2, 3) and lung cancer (4, 5). Several aspergilli, including A. flavus, A. ustus, and A. versicolor, have been identified within the scope of environmental studies, where room air was analyzed to detect fungal pollution in houses (6-8). 2-Pentylfuran (2-PF) was detected in the breath of patients with A. fumigatus infection (9). It was shown that A. fumigatus produces farnesene when grown in vitro (10), and the use of terpene volatiles for the detection of IA has recently been proposed (11). However, the spectrum of volatile organic compounds (VOCs) produced by A. fumigatus and their synthesis have been poorly described. In this work, we characterized the patterns of volatile terpenes produced in vitro by A. fumigatus during growth under saprophytic conditions. In addition, the molecular pathways responsible for the synthesis of terpenoid volatiles were defined. MATERIALS AND METHODS Strains.Aspergillus fumigatus strain FGSC A1163 (ϭ DAL ϭ CBS144.89) was used for wild type strain-based experiments. Gene deletions were obta...

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Section: Figsupporting

confidence: 72%

The Volatome of Aspergillus fumigatus

2014

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“…Alcohol dehydrogenase, aflH (adhA) is a gene located in the AF biosynthetic gene cluster needed for the conversion of 5 0 -hydroxyaverantin to averufin (Chang et al, 2000a). Cuero and Ouellet (2005) measured a gene they called adh1, but it is not clear whether this is the cluster gene or another alcohol dehydrogenase within the fungus; if it is the cluster gene then the transcription of at least two genes in the cluster aflH and aflP are stimulated by the addition of metals.…”

Section: Regulation Of Aflatoxin By Metals/trace Elementsmentioning

confidence: 99%

“…A subtractive cDNA expression library was used in Fusarium graminearium to show that metals cause an increase in transcription among many genes, several of which were involved in cell growth and division. The expression of one gene encoding an alcohol dehydrogenase was measured by RT-PCR and found to increase in metal treated cultures of both F. graminearium and A. flavus (Cuero and Ouellet, 2005). Alcohol dehydrogenase, aflH (adhA) is a gene located in the AF biosynthetic gene cluster needed for the conversion of 5 0 -hydroxyaverantin to averufin (Chang et al, 2000a).…”

Section: Regulation Of Aflatoxin By Metals/trace Elementsmentioning

confidence: 99%

Genetic regulation of aflatoxin biosynthesis: From gene to genome

Georgianna

Payne

2009

Fungal Genetics and Biology

226

191

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“…Likewise, the efficacy of S. cerevisiae as an ideal competent cell (chassis) for glucose sensors has been demonstrated, due to this yeast's vast genetic machinery related to sugar metabolism [22]. Further, the addition of genetic parts such as ADH1 protein, SNF3 transporter, and ribosomal switch TC aptamer, enhances the efficiency and ability of S. cerevisiae to detect different or specific concentrations of glucose [7].…”

Section: Discussionmentioning

confidence: 99%

“…We applied the concepts of synthetic biology in combination with existing scientific methods to produce new a glucose detector. Effective use of constructed molecular sensors produced by synthetic biology to enhance the detection of metals has been reported [22]. The efficacy of in combining existing scientific methods with synthetic biology has been demonstrated [8].…”

mentioning

confidence: 99%

Construct of DNA glucose sensor yeast plasmid for early detection of diabetes

Cuero¹,

Navia²,

Agudelo³

et al. 2017

Integr Obesity Diabetes

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This investigation was aimed at assembling different genetic building blocks to produce a focused DNA sensor to detect proteins related to glucose in blood, in order to diagnose early diabetes using synthetic biology and conventional molecular biology. A glucose DNA sensor was constructed in Saccharomyces cerevisiae using genomic and synthesized sequences and were tested in both, In vivo using human blood plasma sampled, and In vitro using cultural media. The results were based on fluorescence intensity of the DNA sensor and compared with clinical methods. The DNA sensor was highly sensitive when mixed with plasma samples from different patients (i.e., diabetic, pre-diabetic, and normal) showing high fluorescence, and was able to detect a wide concentration range of glucose equivalent to clinical glycaemia values. Expression of proteins pertaining to glucose metabolism production was determined by 2D-DIGE gel electrophoresis-maldi analysis. The glucose sensor produced results less than a minute after being mixed with a drop of a human blood sample. Our results highlight the advantages of using constructed DNA sensors to detect glucose in blood for early diagnosis of diabetes.The yeast DNA glucose sensor was assembled successfully with standardized genetic parts and was able to detect low levels equivalent to clinical glycaemia (<140 mg/ dL), as well as a higher equivalent level of glycaemia (>200 mg/dL). Thus, our sensor can be used for early diagnosis of diabetes or pre-diabetic conditions, thereby allowing for earlier clinical intervention. The direct correlation between levels of glucose and the intensity of fluorescence of the DNA sensor shows the advantage of using this technology in order to identify specific types of diabetic patients. Sometimes, it is difficult to establish accurate correlations with different methods.human blood [7]. These types of sensors are versatile analytical tools that offer advantages over classical analytical methods due to their inherent specificity, selectivity, and simplicity [5]. Most biological and cellular sensors use membrane and cellular proteins that recognize and take up biomarkers from a medium [6]. However, DNA has also been used in molecular biosensors [8,9].Biomarkers for detecting and diagnosing diseases include physical symptoms, mutated DNA and RNA, secreted proteins, processes such as cell death or proliferation, and serum concentrations of small molecules such as cholesterol or, in the case of diabetes, glucose [6].Currently, the most common methods to diagnose diabetes use enzymatic reactions to determine glucose levels [10,11]. These methods measure glucose in whole blood because erythrocytes contain high concentrations of glucose [12]. The methods include the use of glucose oxidase, hexokinase, and glucose dehydrogenase [13][14][15]. The products of these reactions with blood sugar can be determined using colorimetric and spectrophotometric assays or by measuring the electric current produced in the enzyme reactions; the latter is the approach used ...

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Metal ions modulate gene expression and accumulation of the mycotoxins aflatoxin and zearalenone

Cited by 33 publications

References 21 publications

The Volatome of Aspergillus fumigatus

The Volatome of Aspergillus fumigatus

Genetic regulation of aflatoxin biosynthesis: From gene to genome

Construct of DNA glucose sensor yeast plasmid for early detection of diabetes

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