Aspergilli

曲霉
  • 文章类型: Journal Article
    曲霉属物种多样性,由于其分解代谢多样性而被广泛研究,生物技术和生态价值,和致病性。对曲霉菌来说,结构和功能的保护水平令人印象深刻,不管许多(还没有)神秘的基因组元件。我们假设曲霉中存在对应激有反应的保守基因。为了检验曲霉中这种保守的压力调节剂的假设,以整合完善的生物信息学工具的简单计算策略为起点.具体来说,使用了五个基于转录组的有机化合物暴露数据集,覆盖三种不同的曲霉。在确定的上调基因中,只有一个基因在所有条件下表现出相同的反应,AN9181.该基因编码一种蛋白质,该蛋白质包含苯基香豆素苄基醚还原酶样结构域和氮代谢物阻遏物调节子结构域(NmrA)。与不同条件下的亲本菌株相比,该基因的缺失引起了显着的表型改变。具体来说,AN9181的缺失提高了突变体在不同氮源中的代谢活性。所获得的数据支持AN9181在以浓度依赖性方式暴露于芳香族化合物时通过抑制(减慢)齿形芽孢杆菌生长而起作用。两性霉素B的表型相同。AN9181在氧化应激条件下经历了不同的上调。总的来说,数据表明,AN9181,在此指定为NMRB(氮代谢产物抑制调节剂B),在这种条件下,通过负调节生长来建立氧化应激感知的遗传机制。
    Aspergilli comprise a diversity of species that have been extensively studied due to their catabolic diversity, biotechnological and ecological value, and pathogenicity. An impressive level of structural and functional conservation has been shown for aspergilli, regardless of many (yet) cryptic genomic elements. We have hypothesized the existence of conserved genes responsive to stress in aspergilli. To test the hypothesis of such conserved stress regulators in aspergilli, a straightforward computational strategy integrating well-established bioinformatic tools was used as the starting point. Specifically, five transcriptome-based datasets on exposure to organic compounds were used, covering three distinct Aspergillus species. Among the identified up-regulated genes, only one gene showed the same response in all conditions, AN9181. This gene encodes a protein containing a phenylcoumaran benzylic ether reductase-like domain and a Nitrogen metabolite repressor regulator domain (NmrA). Deletion of this gene caused significant phenotypic alterations compared to that of the parental strain across diverse conditions. Specifically, the deletion of AN9181 raised the mutant\'s metabolic activity in different nitrogen sources. The acquired data supports that AN9181 acts by repressing (slowing down) A. nidulans growth when exposed to aromatic compounds in a concentration dependent manner. The same phenotype was observed for amphotericin B. Finally, AN9181 underwent differential upregulation under oxidative stress conditions. Collectively, the data suggest that AN9181, herein assigned as NmrB (Nitrogen Metabolite Repression Regulator B), builds up the genetic machinery of perception of oxidative stress by negatively regulating growth under such conditions.
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  • 文章类型: Journal Article
    曲霉菌种包括各种感染,从侵袭性曲霉病到过敏性疾病,取决于宿主的免疫状态。在这个光谱中,土曲霉因其作为一种值得注意的病原体的出现及其对两性霉素B的内在抗性而脱颖而出。在过去的几十年中,曲霉相关感染的重要性显着增加,特别是随着免疫受损个体数量的增加。流行病学的探索,形态转变,免疫病理学,和新的治疗方法,例如新的抗真菌药物(PC945,olorofim)和使用抗真菌药物和植物化学物质的组合疗法(植物化学物质:槲皮素,紫草,青蒿素),使用免疫疗法调节免疫应答也带来了更好的结果.此外,在COVID-19时代及其后果的背景下,对于免疫功能低下和免疫功能正常的个体,真菌感染已成为一项重大挑战.这归因于在COVID-19感染期间使用免疫抑制疗法和移植病例的增加。因此,这篇综述旨在提供涵盖流行病学的最新概述,发芽事件,免疫病理学,以及针对土曲霉相关感染的新型药物治疗策略。
    Aspergillus species encompass a variety of infections, ranging from invasive aspergillosis to allergic conditions, contingent upon the immune status of the host. In this spectrum, Aspergillus terreus stands out due to its emergence as a notable pathogen and its intrinsic resistance to amphotericin-B. The significance of Aspergillus-associated infections has witnessed a marked increase in the past few decades, particularly with the increasing number of immunocompromised individuals. The exploration of epidemiology, morphological transitions, immunopathology, and novel treatment approaches such as new antifungal drugs (PC945, olorofim) and combinational therapy using antifungal drugs and phytochemicals (Phytochemicals: quercetin, shikonin, artemisinin), also using immunotherapies to modulate immune response has resulted in better outcomes. Furthermore, in the context COVID-19 era and its aftermath, fungal infections have emerged as a substantial challenge for both immunocompromised and immunocompetent individuals. This is attributed to the use of immune-suppressing therapies during COVID-19 infections and the increase in transplant cases. Consequently, this review aims to provide an updated overview encompassing the epidemiology, germination events, immunopathology, and novel drug treatment strategies against Aspergillus terreus-associated infections.
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  • 文章类型: Journal Article
    这项研究旨在隔离,identify,并确定孟加拉国某些地区商品鸡中曲霉的患病率。
    总共50个疑似死鸡的肺样本,包括肉鸡(n=32)和蛋鸡(n=18),年龄在5天至45周之间,是从孟加拉国Gazipur区的家禽养殖场收集的。使用马铃薯葡萄糖琼脂(PDA)基于菌落形态初步鉴定真菌。从可疑菌落中提取DNA。曲霉属。通过属特异性ASAP-1和ASAP-2检测到。曲霉属。然后通过聚合酶链反应筛选黄曲霉(FLA-1和FLA-2),烟曲霉(ASPU和Af3r),和黑曲霉(ASPU和Nilr)。
    曲霉属的总体患病率。为44%(n=22/50;p<0.05)。在Aspergilli中,在10%(n=5/50)的样品中检测到黄曲霉属。同样,烟曲霉和黑曲霉的检出率分别为26%(n=13/50)和8%(n=4/50)。三个样品与一种以上的真菌有关;两种真菌(A.黄花和黑曲霉)在两个样本中,和三种真菌(A.flavus,A.烟,和A.尼日尔)在一个样本中。
    曲霉属的分离和流行。在孟加拉国首次研究了商业鸡。
    UNASSIGNED: This study was designed to isolate, identify, and determine the prevalence of Aspergilli in commercial chicken in selected areas of Bangladesh.
    UNASSIGNED: A total of 50 lung samples from suspected dead chickens, comprising broilers (n = 32) and layers (n = 18), aged between 5 days and 45 weeks, were collected from poultry farms located in the Gazipur district in Bangladesh. Fungi were primarily identified based on the colony morphology using potato dextrose agar (PDA). DNA was extracted from the suspected colonies. Aspegillus spp. was detected by genus-specific ASAP-1 and ASAP-2. Aspergillus spp. were then screened by polymerase chain reaction targeting Aspergillus flavus (FLA-1 and FLA-2), Aspergillus fumigatus (ASPU and Af3r), and Aspergillus niger (ASPU and Nilr).
    UNASSIGNED: The overall prevalence of Aspergillus spp. was 44% (n = 22/50; p < 0.05). Among the Aspergilli, A. flavus was detected in 10% (n = 5/50) of the samples. Similarly, A. fumigatus and A. niger were detected at 26% (n = 13/50) and 8% (n = 4/50) respectively. Three samples were associated with more than one fungus; two fungi (A. flavus and A. niger) were in two samples, and three fungi (A. flavus, A. fumigatus, and A. niger) were in one sample.
    UNASSIGNED: Isolation and prevalence of Aspergillus spp. in commercial chicken were studied for the first time in Bangladesh.
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  • 文章类型: Journal Article
    质膜转运蛋白在营养物质的导入中起着关键作用,包括糖,氨基酸,核碱基,羧酸,和金属离子,围绕真菌细胞。通过胞吞作用选择性去除这些转运蛋白是最重要的调节机制之一,可确保细胞快速适应不断变化的环境(例如,营养波动或不同的压力)。这种机制的核心是蛋白质网络,其中包括与抑制蛋白相关的运输衔接子(ART),该衔接子将泛素连接酶Rsp5与营养转运蛋白和内吞因子联系起来。转运蛋白构象变化,以及其胞质末端/环与质膜脂质之间的动态相互作用,在胞吞过程中也很关键。这里,我们回顾了有关营养转运蛋白内吞作用的分子机制的最新知识和最新发现,在酿酒酵母酵母和某些丝状真菌曲霉中。我们详细阐述了在自然界中发现的动态条件下,紧密调节的内吞作用对细胞适应性的生理重要性,并强调了对该过程的进一步理解和工程对于最大化滴度至关重要。工业生物技术过程中工程细胞工厂的速率和产量(TRY)值。
    Plasma membrane transporters play pivotal roles in the import of nutrients, including sugars, amino acids, nucleobases, carboxylic acids, and metal ions, that surround fungal cells. The selective removal of these transporters by endocytosis is one of the most important regulatory mechanisms that ensures a rapid adaptation of cells to the changing environment (e.g., nutrient fluctuations or different stresses). At the heart of this mechanism lies a network of proteins that includes the arrestin-related trafficking adaptors (ARTs) which link the ubiquitin ligase Rsp5 to nutrient transporters and endocytic factors. Transporter conformational changes, as well as dynamic interactions between its cytosolic termini/loops and with lipids of the plasma membrane, are also critical during the endocytic process. Here, we review the current knowledge and recent findings on the molecular mechanisms involved in nutrient transporter endocytosis, both in the budding yeast Saccharomyces cerevisiae and in some species of the filamentous fungus Aspergillus. We elaborate on the physiological importance of tightly regulated endocytosis for cellular fitness under dynamic conditions found in nature and highlight how further understanding and engineering of this process is essential to maximize titer, rate and yield (TRY)-values of engineered cell factories in industrial biotechnological processes.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    Mycotoxin-producing Aspergilli (Circumdati, Flavi, and Nigri), usually associated with contaminated food, may also cause respiratory disorders and are insufficiently studied in water-damaged indoor environments. Airborne (N = 71) and dust borne (N = 76) Aspergilli collected at post-flood and control locations in Croatia resulted in eleven different species based on their calmodulin marker: A. ochraceus, A. ostianus, A. pallidofulvus, A. sclerotiorum, and A. westerdijkiae (Circumdati); A. flavus (Flavi); and A. tubingensis, A. welwitschiae, A. niger, A. piperis, and A. uvarum (Nigri). Most of the airborne (73%) and dust borne (54%) isolates were found at post-flood locations, and the highest concentrations measured in indoor air (5720 colony-forming units (CFU)/m3) and dust (2.5 × 105 CFU/g) were up to twenty times higher than in the control locations. A. flavus dominated among airborne isolates (25%) at the unrepaired locations, while 56% of the dust borne Aspergilli were identified as A. tubingensis and A. welwitschiae. The ability of identified isolates to produce mycotoxins aflatoxin B1 (AFB1), fumonisin B2 (FB2), and ochratoxin A were assessed by LC-MS analysis. All ochratoxin A (OTA)-producing Circumdati belonged to A. westerdijkiae (13.7 ± 15.81 µg/mL); in the section, FlaviA. flavus produced AFB1 (2.51 ± 5.31 µg/mL), while A. welwitschiae and A. niger (section Nigri) produced FB2 (6.76 ± 13.51 µg/mL and 11.24 ± 18.30 µg/mL, respectively). Water damage dominantly supported the occurrence of aflatoxigenic A. flavus in indoor environments. Yet unresolved, the causal relationship of exposure to indoor Aspergilli and adverse health effects may support the significance of this research.
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  • 文章类型: Comparative Study
    黄曲霉的诱变模式,对寄生曲霉和烟曲霉提取物进行了评价。这些产毒素曲霉菌株是从农业环境中收集的。在没有和有S9mix(外源代谢活化系统)的情况下,对鼠伤寒沙门氏菌菌株TA98,TA100和TA102进行了Ames测试。将这些数据与单独测试的相应纯霉菌毒素或在等浓度的重组混合物中测试的致突变性进行比较,以研究这些分子和/或其他天然代谢物之间的潜在相互作用。至少有3种机制参与这些黄曲霉毒素的诱变反应:首先,添加S9mix后形成AFB1-8,9-环氧化物,第二,氧化损伤的可能形成,如TA102中的显著反应所示,第三,对高剂量的某些提取物或相关霉菌毒素观察到的直接诱变性,因此不涉及外源活化的中间体。除了确定的霉菌毒素(AFB1,AFB2和AFM1),额外的“天然”化合物有助于提取物的全球诱变性。另一方面,当在二元或三元混合物中混合时,AFB2和AFM1负调节AFB1的致突变性。因此,对“天然”混合物致突变性的评估是一个综合参数,可以更好地反映暴露于产毒曲霉的潜在影响。
    The mutagenic patterns of A. flavus, A. parasiticus and A. fumigatus extracts were evaluated. These strains of toxigenic Aspergillus were collected from the agricultural environment. The Ames test was performed on Salmonella typhimurium strains TA98, TA100 and TA102, without and with S9mix (exogenous metabolic activation system). These data were compared with the mutagenicity of the corresponding pure mycotoxins tested alone or in reconstituted mixtures with equivalent concentrations, in order to investigate the potential interactions between these molecules and/or other natural metabolites. At least 3 mechanisms are involved in the mutagenic response of these aflatoxins: firstly, the formation of AFB1-8,9-epoxide upon addition of S9mix, secondly the likely formation of oxidative damage as indicated by significant responses in TA102, and thirdly, a direct mutagenicity observed for higher doses of some extracts or associated mycotoxins, which does not therefore involve exogenously activated intermediates. Besides the identified mycotoxins (AFB1, AFB2 and AFM1), additional \"natural\" compounds contribute to the global mutagenicity of the extracts. On the other hand, AFB2 and AFM1 modulate negatively the mutagenicity of AFB1 when mixed in binary or tertiary mixtures. Thus, the evaluation of the mutagenicity of \"natural\" mixtures is an integrated parameter that better reflects the potential impact of exposure to toxigenic Aspergilli.
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  • 文章类型: Journal Article
    这项研究使用多相方法调查了选定真菌的黄曲霉毒素产生潜力。使用聚合酶链反应扩增真菌的内部转录间隔区。使用常规方法,例如在酵母提取物蔗糖上生长,进一步评估了45株曲霉的黄曲霉毒素产量。β-环糊精中性红干燥椰子琼脂(β-CNRDCA);黄曲霉毒素调节基因的表达以及薄层色谱(TLC)和高效液相色谱(HPLC)的使用。大部分(82.22%)的分离株携带Nor-1基因,55.56%,68.89%,80%拥有ver-1,omt-A,和aflR基因,分别。所有100%的分离株都带有aflJ基因。根据酵母提取物蔗糖培养基(YES)试验,23个分离株产黄曲霉毒素阳性;铵蒸气试验(51%),黄色素产量(75.5%),和β-CNRDCA测试;和蓝色/绿色荧光(57.7%)。基于TLC检测,在HPLC中产生了42.2%的黄曲霉毒素,总黄曲霉毒素(AFTOT)生产浓度范围为6.77-71,453µg/g。从HPLC获得的可检测黄曲霉毒素B1(AFB1)浓度范围为3.76至70,288µg/g;黄曲霉毒素B2(AFB2)为6.77和242.50µg/g;黄曲霉毒素G1(AFG1)为1.87和745.30µg/g;黄曲霉毒素G2(AFG2)为1.67和768.52µg/g。AFTOT污染水平高于欧盟的可容忍限值(4µg/kg)。回归系数为1(R2=1),而曲霉中黄曲霉毒素浓度存在显着差异(p≤0.05)。这项研究报告了先前被称为非黄曲霉毒素生产者的米曲霉产生AFG1,AFG2,AFB1和AFB2毒素的潜力。饲养的动物饲养场中的曲霉能够产生黄曲霉毒素,这可能对健康造成危害。
    This study investigated the aflatoxin production potentials of selected fungi using a polyphasic approach. Internally transcribed spacer region of the fungi was amplified using the polymerase chain reaction. Forty-five Aspergillus strains were further assessed for aflatoxin production using the conventional methods such as growth on yeast extract sucrose, β-cyclodextrin neutral red desiccated coconut agar (β-CNRDCA); expression of the aflatoxin regulatory genes and the use of both thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). A large proportion (82.22%) of the isolates harbored the Nor-1 gene while 55.56%, 68.89%, and 80% possessed the ver-1, omt-A, and aflR genes, respectively. All 100% the isolates harbored the aflJ gene. Twenty-three isolates were positive for aflatoxin production based on the yeast extract sucrose medium (YES) test; ammonium vapor test (51%), yellow pigment production (75.5%), and β-CNRDCA tests; and blue/green fluorescence (57.7%). Based on TLC detection 42.2% produced aflatoxins while in the HPLC, total aflatoxin (AFTOT) production concentrations ranged from 6.77-71,453 µg/g. Detectable aflatoxin B1 (AFB1) concentrations obtained from the HPLC ranged between 3.76 and 70,288 µg/g; 6.77 and 242.50 µg/g for aflatoxin B2 (AFB2); 1.87 and 745.30 µg/g for aflatoxin G1 (AFG1); and 1.67 and 768.52 µg/g for aflatoxin G2 (AFG2). AFTOT contamination levels were higher than European Union tolerable limits (4 µg/kg). The regression coefficient was one (R2 = 1) while significant differences exist in the aflatoxin concentrations of Aspergillus (p ≤ 0.05). This study reports the potentials of Aspergillus oryzae previously known as a non-aflatoxin producer to produce AFG1, AFG2, AFB1, and AFB2 toxins. Aspergillus species in feedlots of animals reared for food are capable of producing aflatoxins which could pose hazards to health.
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  • 文章类型: Journal Article
    我们证明了霉菌毒素杂色霉素(STC)迄今为止未知的特性,可以通过形成独特的聚集体类型(不是由类似的黄曲霉毒素形成)在水性介质中提供均匀的溶液,其特征在于在300-400nm范围内异常强的圆二色性(CD)带。结果表明,这些CD带并非源自固有的STC手性,而是类似于psi-DNACD响应的特殊聚集过程的特定特性。透射电子显微镜(TEM)实验表明,细纤维网络类似于具有螺旋纤维的超分子凝胶结构。通过差示扫描量热法(DSC)对聚集体进行的热力学研究表明,主要聚集过程具有很高的可逆性。我们证明了在345nm处的新型STCpsi-CD带可以在生物相关条件(100纳摩尔浓度)下甚至在海洋盐含量条件下应用,以对STC进行特定和定量监测。此外,我们表明STC与DS-DNA强烈非共价相互作用,可能具有毒性作用,因此与以前的信念相反,需要事先进行酶环氧化。
    We demonstrated the hitherto unknown property of the mycotoxin sterigmatocystin (STC) to provide homogeneous solutions in aqueous medium by forming a unique aggregate type (not formed by analogous aflatoxins), characterized by exceptionally strong circular dichroism (CD) bands in the 300-400 nm range. Results showed that these CD bands do not originate from intrinsic STC chirality but are a specific property of a peculiar aggregation process similar to psi-DNA CD response. Transmission electron microscopy (TEM) experiments revealed a fine fiber network resembling a supramolecular gel structure with helical fibers. Thermodynamic studies of aggregates by differential scanning calorimetry (DSC) revealed high reversibility of the dominant aggregation process. We demonstrated that the novel STC psi-CD band at 345 nm could be applied at biorelevant conditions (100 nanomolar concentration) and even in marine-salt content conditions for specific and quantitative monitoring of STC. Also, we showed that STC strongly non-covalently interacts with ds-DNA with likely toxic effects, thus contrary to the previous belief requiring prior enzyme epoxidation.
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  • 文章类型: Journal Article
    肉桂酸是植物中常见的芳香族化合物,并且在木质素合成中起中心中间体的作用。丝状真菌能够通过多种代谢途径降解肉桂酸。研究得最好的途径之一是肉桂酸非氧化脱羧成苯乙烯。在黑曲霉中,酶肉桂酸脱羧酶(CdcA,正式的阿魏酸脱羧酶)和黄素异戊二烯基转移酶(PadA)一起催化肉桂酸和山梨酸的非氧化脱羧。相应的基因,cdcA和padA,与先前称为山梨酸脱羧酶调节因子(SdrA)的推定转录因子一起聚集在基因组中。虽然预测SdrA参与肉桂酸和山梨酸的非氧化脱羧的调节,这从未进行过功能分析。在这项研究中,A.sdrA的尼日尔缺失突变体,cdcA,进一步研究了SdrA在肉桂酸代谢中的作用。表型分析显示,cdcA,sdrA和padA仅参与肉桂酸和山梨酸的降解,而不是其他相关的芳族化合物所必需的。在不同肉桂酸相关化合物上生长的ΔsdrA的全基因组转录组分析,揭示了额外的目标基因,它们也被cdcA聚集在一起,sdra,和黑曲霉基因组中的padA。使用30个曲霉基因组进行的合成分析表明,在Nigri进化枝的大多数曲霉中,存在保守的肉桂酸脱羧基因簇。群集中缺乏某些基因的曲霉不能在肉桂酸上生长,但仍然可以在相关的芳香化合物上生长,证实了这三个基因对黑曲霉肉桂酸代谢的具体作用。
    Cinnamic acid is an aromatic compound commonly found in plants and functions as a central intermediate in lignin synthesis. Filamentous fungi are able to degrade cinnamic acid through multiple metabolic pathways. One of the best studied pathways is the non-oxidative decarboxylation of cinnamic acid to styrene. In Aspergillus niger, the enzymes cinnamic acid decarboxylase (CdcA, formally ferulic acid decarboxylase) and the flavin prenyltransferase (PadA) catalyze together the non-oxidative decarboxylation of cinnamic acid and sorbic acid. The corresponding genes, cdcA and padA, are clustered in the genome together with a putative transcription factor previously named sorbic acid decarboxylase regulator (SdrA). While SdrA was predicted to be involved in the regulation of the non-oxidative decarboxylation of cinnamic acid and sorbic acid, this was never functionally analyzed. In this study, A. niger deletion mutants of sdrA, cdcA, and padA were made to further investigate the role of SdrA in cinnamic acid metabolism. Phenotypic analysis revealed that cdcA, sdrA and padA are exclusively involved in the degradation of cinnamic acid and sorbic acid and not required for other related aromatic compounds. Whole genome transcriptome analysis of ΔsdrA grown on different cinnamic acid related compounds, revealed additional target genes, which were also clustered with cdcA, sdrA, and padA in the A. niger genome. Synteny analysis using 30 Aspergillus genomes demonstrated a conserved cinnamic acid decarboxylation gene cluster in most Aspergilli of the Nigri clade. Aspergilli lacking certain genes in the cluster were unable to grow on cinnamic acid, but could still grow on related aromatic compounds, confirming the specific role of these three genes for cinnamic acid metabolism of A. niger.
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