Costes Laura H, Lippi Yannick, Naylies Claire, Jamin Emilien L, Genthon Clémence, Bailly Sylviane, Oswald Isabelle P, Bailly Jean-Denis, Puel Olivier
TOXALIM (Research Center in Food Toxicology), Université de Toulouse, INRAE, ENVT, EI-Purpan, Toulouse 31027, France.
Metatoul-AXIOM Platform, MetaboHUB, National Infrastructure for Metabolomics and Fluxomics, Toulouse 31000, France.
J Fungi (Basel). 2021 Dec 9;7(12):1055. doi: 10.3390/jof7121055.
Dimethyl sulfoxide (DSMO) is a simple molecule widely used because of its great solvating ability, but this solvent also has little-known biological effects, especially on fungi. is a notorious pathogenic fungus which may contaminate a large variety of crops worldwide by producing aflatoxins, endangering at the same time food safety and international trade. The aim of this study was to characterize the effect of DMSO on including developmental parameters such as germination and sporulation, as well as its transcriptome profile using high-throughput RNA-sequencing assay and its impact on secondary metabolism (SM). After DMSO exposure, displayed depigmented conidia in a dose-dependent manner. The four-day exposition of cultures to two doses of DMSO, chosen on the basis of depigmentation intensity (35 mM "low" and 282 mM "high"), led to no significant impact on fungal growth, germination or sporulation. However, transcriptomic data analysis showed that 4891 genes were differentially regulated in response to DMSO (46% of studied transcripts). A total of 4650 genes were specifically regulated in response to the highest dose of DMSO, while only 19 genes were modulated upon exposure to the lowest dose. Secondary metabolites clusters genes were widely affected by the DMSO, with 91% of clusters impacted at the highest dose. Among these, aflatoxins, cyclopiazonic acid and ustiloxin B clusters were totally under-expressed. The genes belonging to the AFB1 cluster were the most negatively modulated ones, the two doses leading to 63% and 100% inhibition of the AFB1 production, respectively. The SM analysis also showed the disappearance of ustiloxin B and a 10-fold reduction of cyclopiazonic acid level when was treated by the higher DMSO dose. In conclusion, the present study showed that DMSO impacted widely ' transcriptome, including secondary metabolism gene clusters with the aflatoxins at the head of down-regulated ones. The solvent also inhibits conidial pigmentation, which could illustrate common regulatory mechanisms between aflatoxins and fungal pigment pathways. Because of its effect on major metabolites synthesis, DMSO should not be used as solvent especially in studies testing anti-aflatoxinogenic compounds.
二甲基亚砜(DMSO)是一种简单的分子,因其强大的溶剂化能力而被广泛使用,但这种溶剂也有一些鲜为人知的生物学效应,尤其是对真菌。黄曲霉是一种臭名昭著的致病真菌,它可能通过产生黄曲霉毒素污染全球多种作物,同时危及食品安全和国际贸易。本研究的目的是表征DMSO对黄曲霉的影响,包括发育参数如萌发和孢子形成,以及使用高通量RNA测序分析其转录组图谱及其对次级代谢(SM)的影响。在DMSO处理后,黄曲霉呈现出剂量依赖性的分生孢子色素脱失。基于色素脱失强度选择两种剂量的DMSO对培养物进行为期四天的处理(35 mM“低剂量”和282 mM“高剂量”),结果表明对真菌生长、萌发或孢子形成没有显著影响。然而,转录组数据分析表明,有4891个基因因DMSO而受到差异调节(占研究转录本的46%)。共有4650个基因对最高剂量的DMSO有特异性调节,而暴露于最低剂量时只有19个基因被调节。次级代谢产物簇基因受到DMSO的广泛影响,在最高剂量时91%的簇受到影响。其中,黄曲霉毒素、环匹阿尼酸和串珠镰刀菌素B簇完全下调表达(表达不足)。属于AFB1簇的基因是受负调节最严重的基因,两种剂量分别导致AFB1产量抑制63%和100%。次级代谢分析还表明,当用较高剂量的DMSO处理黄曲霉时,串珠镰刀菌素B消失,环匹阿尼酸水平降低10倍。总之,本研究表明DMSO广泛影响黄曲霉的转录组,包括次级代谢基因簇,其中黄曲霉毒素处于下调基因之首。该溶剂还抑制分生孢子色素沉着,这可能说明了黄曲霉毒素和真菌色素途径之间的共同调节机制。由于其对主要代谢产物合成的影响,DMSO尤其不应在测试抗黄曲霉毒素化合物的研究中用作溶剂。