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The study of fungal species evolved radically with the development of molecular techniques and produced new evidence to understand specific fungal mechanisms such as the production of toxic secondary metabolites. Taking advantage of these technologies to improve food safety, the molecular study of toxinogenic species can help elucidate the mechanisms underlying toxin production and enable the development of new effective strategies to control fungal toxicity. Numerous studies have been made on genes involved in aflatoxin B1 (AFB1) production, one of the most hazardous carcinogenic toxins for humans and animals. The current review presents the roles of these different genes and their possible impact on AFB1 production. We focus on the toxinogenic strains Aspergillus flavus and A. parasiticus, primary contaminants and major producers of AFB1 in crops. However, genetic reports on A. nidulans are also included because of the capacity of this fungus to produce sterigmatocystin, the penultimate stable metabolite during AFB1 production. The aim of this review is to provide a general overview of the AFB1 enzymatic biosynthesis pathway and its link with the genes belonging to the AFB1 cluster. It also aims to illustrate the role of global environmental factors on aflatoxin production and the recent data that demonstrate an interconnection between genes regulated by these environmental signals and aflatoxin biosynthetic pathway.
Isaura Caceres; Anthony Al Khoury; Rhoda El Khoury; Sophie Lorber; Isabelle P. Oswald; André El Khoury; Ali Atoui; Olivier Puel; Jean-Denis Bailly. Aflatoxin Biosynthesis and Genetic Regulation: A Review. Toxins 2020, 12, 150 .
AMA StyleIsaura Caceres, Anthony Al Khoury, Rhoda El Khoury, Sophie Lorber, Isabelle P. Oswald, André El Khoury, Ali Atoui, Olivier Puel, Jean-Denis Bailly. Aflatoxin Biosynthesis and Genetic Regulation: A Review. Toxins. 2020; 12 (3):150.
Chicago/Turabian StyleIsaura Caceres; Anthony Al Khoury; Rhoda El Khoury; Sophie Lorber; Isabelle P. Oswald; André El Khoury; Ali Atoui; Olivier Puel; Jean-Denis Bailly. 2020. "Aflatoxin Biosynthesis and Genetic Regulation: A Review." Toxins 12, no. 3: 150.
Aspergillus flavus, a soil-borne pathogen, represents a danger for humans and animals since it produces the carcinogenic mycotoxin Aflatoxin B1 (AFB1). Approaches aiming the reduction of this fungal contaminant mainly involve chemicals that may also be toxic. Therefore, identification and characterization of natural anti-aflatoxigenic products represents a sustainable alternative strategy. Piperine, a major component of black and long peppers, has been previously demonstrated asan AFB1-inhibitor; nevertheless its mechanism of action was yet to be elucidated. The aim of the present study was to evaluate piperine's molecular mechanism of action in A. flavus with a special focus on oxidative stress response. For that, the entire AFB1 gene cluster as well asa targeted gene-network coding for fungal stress response factors and cellular receptors were analyzed. In addition to this, fungal enzymatic activities were also characterized. We demonstrated that piperine inhibits aflatoxin production and fungal growth in a dose-dependent manner. Analysis of the gene cluster demonstrated that almost all genes participating in aflatoxin's biosynthetic pathway were down regulated. Exposure to piperine also resulted in decreased transcript levels of the global regulator veA together with an over-expression of genes coding for several basic leucine zipper (bZIP) transcription factors such as atfA, atfB and ap-1 and genes belonging to superoxide dismutase and catalase's families. Furthermore, this gene response was accompanied by a significant enhancement of catalase enzymatic activity. In conclusion, these data demonstrated that piperine inhibits AFB1 production while positively modulating fungal antioxidant status in A. flavus.
Isaura Caceres; Rhoda El Khoury; Sylviane Bailly; Isabelle P. Oswald; Olivier Puel; Jean-Denis Bailly. Piperine inhibits aflatoxin B1 production in Aspergillus flavus by modulating fungal oxidative stress response. Fungal Genetics and Biology 2017, 107, 77 -85.
AMA StyleIsaura Caceres, Rhoda El Khoury, Sylviane Bailly, Isabelle P. Oswald, Olivier Puel, Jean-Denis Bailly. Piperine inhibits aflatoxin B1 production in Aspergillus flavus by modulating fungal oxidative stress response. Fungal Genetics and Biology. 2017; 107 ():77-85.
Chicago/Turabian StyleIsaura Caceres; Rhoda El Khoury; Sylviane Bailly; Isabelle P. Oswald; Olivier Puel; Jean-Denis Bailly. 2017. "Piperine inhibits aflatoxin B1 production in Aspergillus flavus by modulating fungal oxidative stress response." Fungal Genetics and Biology 107, no. : 77-85.
Of all the food-contaminating mycotoxins, aflatoxins, and most notably aflatoxin B1 (AFB1), are found to be the most toxic and economically costly. Green farming is striving to replace fungicides and develop natural preventive strategies to minimize crop contamination by these toxic fungal metabolites. In this study, we demonstrated that an aqueous extract of the medicinal plant Micromeria graeca—known as hyssop—completely inhibits aflatoxin production by Aspergillus flavus without reducing fungal growth. The molecular inhibitory mechanism was explored by analyzing the expression of 61 genes, including 27 aflatoxin biosynthesis cluster genes and 34 secondary metabolism regulatory genes. This analysis revealed a three-fold down-regulation of aflR and aflS encoding the two internal cluster co-activators, resulting in a drastic repression of all aflatoxin biosynthesis genes. Hyssop also targeted fifteen regulatory genes, including veA and mtfA, two major global-regulating transcription factors. The effect of this extract is also linked to a transcriptomic variation of several genes required for the response to oxidative stress such as msnA, srrA, catA, cat2, sod1, mnsod, and stuA. In conclusion, hyssop inhibits AFB1 synthesis at the transcriptomic level. This aqueous extract is a promising natural-based solution to control AFB1 contamination.
Rhoda El Khoury; Isaura Caceres; Olivier Puel; Sylviane Bailly; Ali Atoui; Isabelle P. Oswald; André El Khoury; Jean-Denis Bailly. Identification of the Anti-Aflatoxinogenic Activity of Micromeria graeca and Elucidation of Its Molecular Mechanism in Aspergillus flavus. Toxins 2017, 9, 87 .
AMA StyleRhoda El Khoury, Isaura Caceres, Olivier Puel, Sylviane Bailly, Ali Atoui, Isabelle P. Oswald, André El Khoury, Jean-Denis Bailly. Identification of the Anti-Aflatoxinogenic Activity of Micromeria graeca and Elucidation of Its Molecular Mechanism in Aspergillus flavus. Toxins. 2017; 9 (3):87.
Chicago/Turabian StyleRhoda El Khoury; Isaura Caceres; Olivier Puel; Sylviane Bailly; Ali Atoui; Isabelle P. Oswald; André El Khoury; Jean-Denis Bailly. 2017. "Identification of the Anti-Aflatoxinogenic Activity of Micromeria graeca and Elucidation of Its Molecular Mechanism in Aspergillus flavus." Toxins 9, no. 3: 87.
Produced by several species of Aspergillus, Aflatoxin B1 (AFB1) is a carcinogenic mycotoxin contaminating many crops worldwide. The utilization of fungicides is currently one of the most common methods; nevertheless, their use is not environmentally or economically sound. Thus, the use of natural compounds able to block aflatoxinogenesis could represent an alternative strategy to limit food and feed contamination. For instance, eugenol, a 4-allyl-2-methoxyphenol present in many essential oils, has been identified as an anti-aflatoxin molecule. However, its precise mechanism of action has yet to be clarified. The production of AFB1 is associated with the expression of a 70 kB cluster, and not less than 21 enzymatic reactions are necessary for its production. Based on former empirical data, a molecular tool composed of 60 genes targeting 27 genes of aflatoxin B1 cluster and 33 genes encoding the main regulatory factors potentially involved in its production, was developed. We showed that AFB1 inhibition in Aspergillus flavus following eugenol addition at 0.5 mM in a Malt Extract Agar (MEA) medium resulted in a complete inhibition of the expression of all but one gene of the AFB1 biosynthesis cluster. This transcriptomic effect followed a down-regulation of the complex composed by the two internal regulatory factors, AflR and AflS. This phenomenon was also influenced by an over-expression of veA and mtfA, two genes that are directly linked to AFB1 cluster regulation.
Isaura Caceres; Rhoda El Khoury; Ángel Medina; Yannick Lippi; Claire Naylies; Ali Atoui; André El Khoury; Isabelle P. Oswald; Jean-Denis Bailly; Olivier Puel. Deciphering the Anti-Aflatoxinogenic Properties of Eugenol Using a Large-Scale q-PCR Approach. Toxins 2016, 8, 123 .
AMA StyleIsaura Caceres, Rhoda El Khoury, Ángel Medina, Yannick Lippi, Claire Naylies, Ali Atoui, André El Khoury, Isabelle P. Oswald, Jean-Denis Bailly, Olivier Puel. Deciphering the Anti-Aflatoxinogenic Properties of Eugenol Using a Large-Scale q-PCR Approach. Toxins. 2016; 8 (5):123.
Chicago/Turabian StyleIsaura Caceres; Rhoda El Khoury; Ángel Medina; Yannick Lippi; Claire Naylies; Ali Atoui; André El Khoury; Isabelle P. Oswald; Jean-Denis Bailly; Olivier Puel. 2016. "Deciphering the Anti-Aflatoxinogenic Properties of Eugenol Using a Large-Scale q-PCR Approach." Toxins 8, no. 5: 123.