Dozolme Pascale Marie Aimée, Moukha Serge Maria
Centre de Recherche Cardio-Thoracique de Bordeaux, INSERM U1045/INRAE, Plateforme Technologique d'Innovation Biomédicale (PTIB), Hôpital Xavier Arnozan, Université de Bordeaux, Bordeaux, France.
Front Microbiol. 2020 Oct 30;11:562754. doi: 10.3389/fmicb.2020.562754. eCollection 2020.
This study presents fungi infrequently viewed as fungal factories for secondary metabolite production resources such as mycotoxins in . Additionally, we demonstrated that biochemical warfare of factory against animal cells is not only due to mycotoxins such as fumonisins, but acute cytotoxic firing is based on different excreted secondary metabolite series, potentially leading to animal and human diseases. In this study, fumonisins, which can be followed by localization, quantification, or expression of the key gene implicated in their synthesis, are used to understand secondary metabolite production by this fungus. It is known that produces mycotoxins such as fumonisins on cereals, but until now, there is no evidence demonstrating a method to totally block fumonisin production on feed and food. In this paper, we explained, what was never clearly established before, that fumonisin production depends on two bottlenecks. The fumonisin synthesis and secretion in fungal articles of the mycelium are medium-independent and follow the fungal cell cycle developmental program (ontogenesis). Conversely, the fumonisin excretion into the medium depends on its composition, which also impacts fumonisin biosynthesis level. Using a high-pressure freezing method, we showed that, in non-permissive fumonisin excretion (NPFE) medium, FB1 is sequestered inside extra-vesicles and in the first third of the cell wall next to the plasmalemma, leading to the hypothesis that the fungus develops mechanisms to protect its cytosolic homeostasis against this cytotoxic. In permissive fumonisin excretion (PFE) medium, leading to very high quantities of excreted fumonisins, FB1 localized inside extra-vesicles, crosses the entire cell wall thickness, and then releases into the medium. Our results demonstrated a delayed and lower expression of gene in mycelium developed on NPFE medium as compared to PFE medium. Conversely, higher amounts of fumonisins were accumulated in NPFE-grown mycelium than in PFE-grown mycelium. Thus, our results demonstrated for the first time that we have to take into account that the synthesis and secretion inside the article of secondary metabolites depend on the occurrence of cryptic biochemical specialized articles, differentiated in the mycelium. However, those are not morphologically different from other colonial hyphae.
本研究展示了一些真菌，这些真菌在产毒方面常被视为不常见的真菌工厂，可产生如霉菌毒素等次生代谢产物。此外，我们证明了这种真菌工厂对动物细胞的生化攻击不仅源于伏马菌素等霉菌毒素，而且急性细胞毒性作用还基于不同的分泌次生代谢产物系列，这可能导致动物和人类疾病。在本研究中，伏马菌素可通过其定位、定量或参与其合成的关键基因的表达来追踪，以此了解该真菌的次生代谢产物产生情况。已知该真菌在谷物上会产生伏马菌素等霉菌毒素，但到目前为止，尚无证据表明存在一种能完全阻断饲料和食品中伏马菌素产生的方法。在本文中，我们解释了此前从未明确证实的一点，即伏马菌素的产生取决于两个瓶颈因素。在真菌菌丝体中，伏马菌素的合成和分泌不依赖于培养基，而是遵循真菌细胞周期发育程序（个体发育）。相反，伏马菌素向培养基中的排泄取决于培养基的成分，这也会影响伏马菌素的生物合成水平。通过高压冷冻方法，我们发现，在非允许伏马菌素排泄（NPFE）培养基中，伏马菌素B1（FB1）被隔离在细胞外囊泡内以及紧邻质膜的细胞壁前三分之一处，这引发了一种假设，即真菌会形成保护其细胞溶质内稳态免受这种细胞毒性影响的机制。在允许伏马菌素排泄（PFE）培养基中，会导致大量伏马菌素分泌，FB1定位在细胞外囊泡内，穿过整个细胞壁厚度，然后释放到培养基中。我们的结果表明，与PFE培养基相比，在NPFE培养基上生长的菌丝体中该基因的表达延迟且较低。相反，在NPFE培养基上生长的菌丝体中积累的伏马菌素量比在PFE培养基上生长的菌丝体中更多。因此，我们的结果首次证明，我们必须考虑到次生代谢产物在菌体内的合成和分泌取决于在菌丝体中分化出的隐秘生化特化结构的存在。然而，这些结构在形态上与其他菌落菌丝并无差异。
