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
    从生物学和进化研究中升级的真菌基因组分析。推定的酶的生化分析将不可避免地滞后,并且仅对选择进行表征。植物病原真菌分泌锰-脂氧合酶(MnLOX),将不饱和脂肪酸氧化为氢过氧化物以支持感染。到目前为止,已经对六个MnLOX进行了表征,包括稻瘟病和Take-all真菌的这些酶的3D结构。目的是使用这些信息来评估MnLOX相关的基因转录本,以找到用于进一步研究的信息样本。系统发育分析,催化活性的决定因素,和C端氨基酸序列将54个转录本分为三个主要亚家族。六个MnLOX属于相同的“原型”亚家族,在催化决定簇和C末端序列中具有保守的残基。第二个亚家族保留了分泌机制,推测是吸收Mn2+所必需的,但在催化决定簇和半胱氨酸置换不变的Leu残基以定位(“钳制”)脂肪酸方面有所不同。第三个亚家族与区域特异性氧化的Gly/Ala开关中的丙氨酸形成对比,少数包含前所未有的C末端序列或缺乏分泌信号。除了这些例外,三个亚家族转录本的生化分析似乎具有找到活性酶的合理前景。
    Analyses of fungal genomes of escalate from biological and evolutionary investigations. The biochemical analyses of putative enzymes will inevitably lag behind and only a selection will be characterized. Plant-pathogenic fungi secrete manganese-lipoxygenases (MnLOX), which oxidize unsaturated fatty acids to hydroperoxides to support infection. Six MnLOX have been characterized so far including the 3D structures of these enzymes of the Rice blast and the Take-all fungi. The goal was to use this information to evaluate MnLOX-related gene transcripts to find informative specimens for further studies. Phylogenetic analysis, determinants of catalytic activities, and the C-terminal amino acid sequences divided 54 transcripts into three major subfamilies. The six MnLOX belonged to the same \"prototype\" subfamily with conserved residues in catalytic determinants and C-terminal sequences. The second subfamily retained the secretion mechanism, presumably necessary for uptake of Mn2+, but differed in catalytic determinants and by cysteine replacement of an invariant Leu residue for positioning (\"clamping\") of fatty acids. The third subfamily contrasted with alanine in the Gly/Ala switch for regiospecific oxidation and a minority contained unprecedented C-terminal sequences or lacked secretion signals. With these exceptions, biochemical analyses of transcripts of the three subfamilies appear to have reasonable prospects to find active enzymes.
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  • 文章类型: Journal Article
    DNA和组蛋白的化学修饰会影响核内染色质的组织。这些修改的变化,由不同的染色质修饰酶催化,影响染色质组织,这反过来被认为会影响基因表达的时空调控。虽然不同组蛋白修饰的组合,组蛋白密码,已经在几个模型物种中进行了研究,我们对曲霉菌属的组蛋白修饰知之甚少,由于其在细胞和分子生物学中作为模型的重要性以及其医学和生物技术相关性,其成员通常得到了很好的研究。这里,我们在94种曲霉和其他真菌中进行了系统发育分析,以揭示在染色质修饰或调节中起作用的酶和蛋白质复合物的发生和进化轨迹。我们发现这些酶和复合物在曲霉中高度保守,指向复杂的染色质修饰库。然而,我们还观察到最近很少有基因重复或丢失,突出曲霉属物种以进一步研究特定染色质修饰的作用。SET7(KMT6)和PRC2(多梳抑制复合物2)的其他成分,在包括真菌在内的许多真核生物中,赖氨酸27处组蛋白H3的甲基化负责,在曲霉属以及密切相关的青霉属物种中都不存在,表明这些失去了这种组蛋白修饰的能力。我们通过对构巢曲霉中的组蛋白翻译后修饰进行非靶向MS分析来证实我们的计算预测。这种系统分析将为将来研究组蛋白密码的复杂性及其对真菌基因组结构和基因调控的功能影响铺平道路。
    Chemical modifications of DNA and histone proteins impact the organization of chromatin within the nucleus. Changes in these modifications, catalysed by different chromatin-modifying enzymes, influence chromatin organization, which in turn is thought to impact the spatial and temporal regulation of gene expression. While combinations of different histone modifications, the histone code, have been studied in several model species, we know very little about histone modifications in the fungal genus Aspergillus, whose members are generally well studied due to their importance as models in cell and molecular biology as well as their medical and biotechnological relevance. Here, we used phylogenetic analyses in 94 Aspergilli as well as other fungi to uncover the occurrence and evolutionary trajectories of enzymes and protein complexes with roles in chromatin modifications or regulation. We found that these enzymes and complexes are highly conserved in Aspergilli, pointing towards a complex repertoire of chromatin modifications. Nevertheless, we also observed few recent gene duplications or losses, highlighting Aspergillus species to further study the roles of specific chromatin modifications. SET7 (KMT6) and other components of PRC2 (Polycomb Repressive Complex 2), which is responsible for methylation on histone H3 at lysine 27 in many eukaryotes including fungi, are absent in Aspergilli as well as in closely related Penicillium species, suggesting that these lost the capacity for this histone modification. We corroborated our computational predictions by performing untargeted MS analysis of histone post-translational modifications in Aspergillus nidulans. This systematic analysis will pave the way for future research into the complexity of the histone code and its functional implications on genome architecture and gene regulation in fungi.
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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
    在组合去铁蛋白-H2O2(铁螯合-氧化)胁迫下研究了属于9种的14种曲霉菌株的生长。当去铁酮预处理的菌丝体受到甚至弱的氧化应激时,14个菌株中有10个增强了铁螯合胁迫的生长抑制作用。相比之下,分生孢子的氧化应激预处理增加了10个菌株的去铁剂耐受性。使用铁螯合剂作为抗真菌剂或佐剂可以提高免疫系统的联合铁戒断-氧化应激策略的效率,并可能减少从肺巨噬细胞的氧化攻击中逃脱的分生孢子的存活。
    The growth of 14 Aspergillus strains belonging to nine species was studied under combinatorial deferriprone - H2O2 (iron-chelation - oxidative) stress. When deferriprone pretreated mycelia were subjected to even a weak oxidative stress, the growth inhibitory effect of iron-chelation stress was enhanced in 10 out of 14 strains. In contrast, oxidative stress pretreatment of conidia increased their deferriprone tolerance in 10 strains. Applying iron-chelators as antifungal agent or adjuvant can enhance the efficiency of the combinatorial iron withdrawal - oxidative stress strategy of our immune system and may reduce the survival of conidia escaped from the oxidative attack of pulmonary macrophages.
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  • 文章类型: Journal Article
    Contrary to the opinion recently offered by Dimou et al., our previously published biochemical, subcellular and genetic data supported our contention that AN11127 corresponds to the A. nidulans gene encoding Sec12, which is the guanine nucleotide exchange factor (GEF) specific for SAR1. We add here additional bioinformatics evidence that fully disprove the otherwise negative evidence reported by Dimou et al., highlighting the dangers associated with the lax interpretation of genomic data. On the positive side, we establish guidelines for the identification of this key secretory gene in other species of Ascomycota and Basidiomycota, including species of medical and applied interest.
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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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