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Editorial: Co-morbidity of COVID 19 and fungal infections. 社论:COVID 19 和真菌感染的并发症。
IF 2.1 Q3 MYCOLOGY Pub Date : 2024-09-16 eCollection Date: 2024-01-01 DOI: 10.3389/ffunb.2024.1462172
Ramendra Pati Pandey, Ruby Dhiman, Vivek Mishra, V Samuel Raj, Chung-Ming Chang
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引用次数: 0
Fungi of Great Salt Lake, Utah, USA: a spatial survey. 美国犹他州大盐湖的真菌:空间调查。
IF 2.1 Q3 MYCOLOGY Pub Date : 2024-09-13 eCollection Date: 2024-01-01 DOI: 10.3389/ffunb.2024.1438347
David L Parrott, Bonnie K Baxter

The natural system at Great Salt Lake, Utah, USA was augmented by the construction of a rock-filled railroad causeway in 1960, creating two lakes at one site. The north arm is sequestered from the mountain snowmelt inputs and thus became saturated with salts (250-340 g/L). The south arm is a flourishing ecosystem with moderate salinity (90-190 g/L) and a significant body of water for ten million birds on the avian flyways of the western US who engorge themselves on the large biomass of brine flies and shrimp. The sediments around the lake shores include calcium carbonate oolitic sand and clay, and further away from the saltwater margins, a zone with less saline soil. Here a small number of plants can thrive, including Salicornia and Sueda species. At the north arm at Rozel Point, halite crystals precipitate in the salt-saturated lake water, calcium sulfate precipitates to form gypsum crystals embedded in the clay, and high molecular weight asphalt seeps from the ground. It is an ecosystem with gradients and extremes, and fungi are up to the challenge. We have collected data on Great Salt Lake fungi from a variety of studies and present them here in a spatial survey. Combining knowledge of cultivation studies as well as environmental DNA work, we discuss the genera prevalent in and around this unique ecosystem. A wide diversity of taxa were found in multiple microniches of the lake, suggesting significant roles for these genera: Acremonium, Alternaria, Aspergillus, Cladosporium, Clydae, Coniochaeta, Cryptococcus, Malassezia, Nectria, Penicillium, Powellomyces, Rhizophlyctis, and Wallemia. Considering the species present and the features of Great Salt Lake as a terminal basin, we discuss of the possible roles of the fungi. These include not only nutrient cycling, toxin mediation, and predation for the ecosystem, but also roles that would enable other life to thrive in the water and on the shore. Many genera that we discovered may help other organisms in alleviating salinity stress, promoting growth, or affording protection from dehydration. The diverse taxa of Great Salt Lake fungi provide important benefits for the ecosystem.

美国犹他州大盐湖的自然系统在 1960 年修建了一条填满岩石的铁路堤道,从而在一个地点形成了两个湖泊。北侧的湖泊受到高山融雪的阻隔,因此盐分饱和(250-340 克/升)。南臂是一个繁荣的生态系统,盐度适中(90-190 克/升),是美国西部鸟类迁徙路线上千万只鸟类的重要水域,这些鸟类在这里捕食大量的卤水蝇和虾。湖岸周围的沉积物包括碳酸钙鲕状沙和粘土,离咸水边缘更远的地方则是盐碱较少的土壤区。这里有少量植物可以繁衍生息,包括盐生植物和水田植物。在罗泽尔角的北臂,盐饱和的湖水中会析出海绿石晶体,硫酸钙析出形成石膏晶体嵌在粘土中,高分子量的沥青从地下渗出。这是一个具有梯度和极端性的生态系统,而真菌可以应对这一挑战。我们从各种研究中收集了有关大盐湖真菌的数据,并在这里以空间调查的形式展示出来。结合栽培研究和环境 DNA 工作的知识,我们讨论了这一独特生态系统中及周边地区普遍存在的菌属。我们在湖泊的多个微区发现了多种分类群,这表明这些菌属发挥了重要作用:这些菌属包括:Acremonium、Alternaria、Aspergillus、Cladosporium、Clydae、Coniochaeta、Cryptococcus、Malassezia、Nectria、Penicillium、Powellomyces、Rhizophlyctis 和 Wallemia。考虑到存在的物种和大盐湖作为终端流域的特点,我们讨论了真菌可能发挥的作用。这些作用不仅包括营养循环、毒素调解和生态系统捕食,还包括使其他生物在水中和岸上繁衍生息的作用。我们发现的许多菌属可能有助于其他生物减轻盐度压力、促进生长或提供脱水保护。大盐湖真菌类群的多样性为生态系统提供了重要的益处。
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引用次数: 0
Editorial: Fungal toxic secondary metabolites in foods and feeds: recent sustainable analytical techniques and innovative preventative and remediation strategies for their formation and toxicity. 社论:食品和饲料中的真菌有毒次生代谢物:针对其形成和毒性的最新可持续分析技术及创新性预防和补救策略。
IF 2.1 Q3 MYCOLOGY Pub Date : 2024-09-12 eCollection Date: 2024-01-01 DOI: 10.3389/ffunb.2024.1442327
Dikabo Mogopodi, Olubukola Oluranti Babalola, Titus A M Msagati
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引用次数: 0
In Rhodotorula mucilaginosa, active oxidative metabolism increases carotenoids to inactivate excess reactive oxygen species. 在粘毛杜鹃花中,活跃的氧化代谢增加了类胡萝卜素,以灭活过量的活性氧。
IF 2.1 Q3 MYCOLOGY Pub Date : 2024-09-06 eCollection Date: 2024-01-01 DOI: 10.3389/ffunb.2024.1378590
Edson Mosqueda-Martínez, Natalia Chiquete-Félix, Paulina Castañeda-Tamez, Carolina Ricardez-García, Manuel Gutiérrez-Aguilar, Salvador Uribe-Carvajal, Ofelia Mendez-Romero

Carotenoids produced by bacteria, yeasts, algae and plants inactivate Free Radicals (FR). However, FR may inactivate carotenoids and even turn them into free radicals. Oxidative metabolism is a source of the highly motile Reactive Oxygen Species (ROS). To evaluate carotenoid interactions with ROS, the yeast Rhodotorula mucilaginosa was grown in dextrose (YPD), a fermentative substrate where low rates of oxygen consumption and low carotenoid expression were observed, or in lactate (YPLac), a mitochondrial oxidative-phosphorylation (OxPhos) substrate, which supports high respiratory activity and carotenoid production. ROS were high in YPLac-grown cells and these were unmasked by the carotenoid production-inhibitor diphenylamine (DPA). In contrast, in YPD-grown cells ROS were almost absent. It is proposed that YPLac cells are under oxidative stress. In addition, YPLac-grown cells were more sensitive than YPD-grown cells to menadione (MD), a FR-releasing agent. To test whether carotenoids from cells grown in YPLac had been modified by ROS, carotenoids from each, YPD- and YPLac-grown cells were isolated and added back to cells, evaluating protection from MD. Remarkably, carotenoids extracted from cells grown in YPLac medium inhibited growth, while in contrast extracts from YPD-grown cells were innocuous or mildly protective. Results suggest that carotenoid-synthesis in YPLac-cells is a response to OxPhos-produced ROS. However, upon reacting with FR, carotenoids themselves may be inactivated or even become prooxidant themselves.

细菌、酵母、藻类和植物产生的类胡萝卜素可使自由基(FR)失活。然而,自由基可能会使类胡萝卜素失活,甚至将其转化为自由基。氧化代谢是活性氧(ROS)的来源之一。为了评估类胡萝卜素与 ROS 的相互作用,将粘质酵母(Rhodotorula mucilaginosa)置于葡萄糖(YPD)或乳酸盐(YPLac)中进行培养,前者是一种发酵底物,耗氧量低,类胡萝卜素表达量也低;后者是一种线粒体氧化磷酸化(OxPhos)底物,支持高呼吸活性和类胡萝卜素的产生。在 YPLac 生长的细胞中,ROS 含量很高,类胡萝卜素生成抑制剂二苯胺(DPA)可以消除 ROS。相反,在 YPD 生长的细胞中,ROS 几乎不存在。这表明 YPLac 细胞处于氧化压力下。此外,YPLac 生长的细胞比 YPD 生长的细胞对甲萘醌(MD)(一种 FR 释放剂)更敏感。为了测试在 YPLac 生长的细胞中的类胡萝卜素是否被 ROS 改变,我们分别从 YPD 和 YPLac 生长的细胞中分离出类胡萝卜素,并将其添加回细胞中,评估其对 MD 的保护作用。值得注意的是,从 YPLac 培养基中生长的细胞中提取的类胡萝卜素会抑制生长,而从 YPD 生长的细胞中提取的类胡萝卜素则无害或具有轻微的保护作用。结果表明,YPLac 细胞中类胡萝卜素的合成是对 OxPhos 产生的 ROS 的反应。然而,类胡萝卜素本身在与 FR 反应后可能会失活,甚至变成促氧化剂。
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引用次数: 0
Comparative genomics of the extremophile Cryomyces antarcticus and other psychrophilic Dothideomycetes. 嗜极隐杆线虫与其他精神嗜性齿孢菌的比较基因组学。
IF 2.1 Q3 MYCOLOGY Pub Date : 2024-09-06 eCollection Date: 2024-01-01 DOI: 10.3389/ffunb.2024.1418145
Sandra V Gomez-Gutierrrez, Wily R Sic-Hernandez, Sajeet Haridas, Kurt LaButti, Joanne Eichenberger, Navneet Kaur, Anna Lipzen, Kerrie Barry, Stephen B Goodwin, Michael Gribskov, Igor V Grigoriev

Over a billion years of fungal evolution has enabled representatives of this kingdom to populate almost all parts of planet Earth and to adapt to some of its most uninhabitable environments including extremes of temperature, salinity, pH, water, light, or other sources of radiation. Cryomyces antarcticus is an endolithic fungus that inhabits rock outcrops in Antarctica. It survives extremes of cold, humidity and solar radiation in one of the least habitable environments on Earth. This fungus is unusual because it produces heavily melanized, meristematic growth and is thought to be haploid and asexual. Due to its growth in the most extreme environment, it has been suggested as an organism that could survive on Mars. However, the mechanisms it uses to achieve its extremophilic nature are not known. Comparative genomics can provide clues to the processes underlying biological diversity, evolution, and adaptation. This effort has been greatly facilitated by the 1000 Fungal Genomes project and the JGI MycoCosm portal where sequenced genomes have been assembled into phylogenetic and ecological groups representing different projects, lifestyles, ecologies, and evolutionary histories. Comparative genomics within and between these groups provides insights into fungal adaptations, for example to extreme environmental conditions. Here, we analyze two Cryomyces genomes in the context of additional psychrophilic fungi, as well as non-psychrophilic fungi with diverse lifestyles selected from the MycoCosm database. This analysis identifies families of genes that are expanded and contracted in Cryomyces and other psychrophiles and may explain their extremophilic lifestyle. Higher GC contents of genes and of bases in the third positions of codons may help to stabilize DNA under extreme conditions. Numerous smaller contigs in C. antarcticus suggest the presence of an alternative haplotype that could indicate the sequenced isolate is diploid or dikaryotic. These analyses provide a first step to unraveling the secrets of the extreme lifestyle of C. antarcticus.

经过十多亿年的真菌进化,这个王国的代表物种几乎遍布地球的各个角落,并能适应地球上一些最不适宜人类居住的环境,包括极端的温度、盐度、pH 值、水、光或其他辐射源。南极隐球菌是一种内生真菌,栖息在南极洲的岩石露头上。它能在地球上最不适宜居住的环境中的极端寒冷、潮湿和太阳辐射条件下生存。这种真菌之所以与众不同,是因为它能产生大量黑色分生组织,而且被认为是单倍体和无性生殖。由于它能在最极端的环境中生长,有人认为它是一种可以在火星上生存的生物。然而,它实现嗜极性的机制尚不清楚。比较基因组学可以为生物多样性、进化和适应过程提供线索。1000 真菌基因组》项目和 JGI MycoCosm 门户网站极大地推动了这项工作,在这两个门户网站上,已测序的基因组被组合成系统发育和生态组,代表了不同的项目、生活方式、生态学和进化史。这些组内和组间的比较基因组学提供了对真菌适应性的深入了解,例如对极端环境条件的适应性。在这里,我们结合从 MycoCosm 数据库中选取的其他嗜心理真菌以及具有不同生活方式的非嗜心理真菌,分析了两个隐杯霉菌基因组。这项分析确定了在隐鞭毛霉菌和其他嗜精神真菌中扩展和收缩的基因家族,这可能解释了它们的嗜极端生活方式。基因和密码子第三位碱基的 GC 含量较高,这可能有助于在极端条件下稳定 DNA。南极蝇中大量较小的等位基因表明存在另一种单倍型,这可能表明测序分离物是二倍体或二核生物。这些分析为揭开南极蝇极端生活方式的秘密迈出了第一步。
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引用次数: 0
Navigating the fungal battlefield: cysteine-rich antifungal proteins and peptides from Eurotiales. 在真菌战场上航行:欧洲藻类中富含半胱氨酸的抗真菌蛋白和肽。
IF 2.1 Q3 MYCOLOGY Pub Date : 2024-09-03 eCollection Date: 2024-01-01 DOI: 10.3389/ffunb.2024.1451455
Jeanett Holzknecht, Florentine Marx

Fungi are ubiquitous in the environment and play a key role in the decomposition and recycling of nutrients. On the one hand, their special properties are a great asset for the agricultural and industrial sector, as they are used as source of nutrients, producers of enzymes, pigments, flavorings, and biocontrol agents, and in food processing, bio-remediation and plant growth promotion. On the other hand, they pose a serious challenge to our lives and the environment, as they are responsible for fungal infections in plants, animals and humans. Although host immunity opposes invading pathogens, certain factors favor the manifestation of fungal diseases. The prevalence of fungal infections is on the rise, and there is an alarming increase in the resistance of fungal pathogens to approved drugs. The limited number of antimycotics, the obstacles encountered in the development of new drugs due to the poor tolerability of antifungal agents in patients, the limited number of unique antifungal targets, and the low species specificity contribute to the gradual depletion of the antifungal pipeline and newly discovered antifungal drugs are rare. Promising candidates as next-generation therapeutics are antimicrobial proteins and peptides (AMPs) produced by numerous prokaryotic and eukaryotic organisms belonging to all kingdom classes. Importantly, filamentous fungi from the order Eurotiales have been shown to be a rich source of AMPs with specific antifungal activity. A growing number of published studies reflects the efforts made in the search for new antifungal proteins and peptides (AFPs), their efficacy, species specificity and applicability. In this review, we discuss important aspects related to fungi, their impact on our life and issues involved in treating fungal infections in plants, animals and humans. We specifically highlight the potential of AFPs from Eurotiales as promising alternative antifungal therapeutics. This article provides insight into the structural features, mode of action, and progress made toward their potential application in a clinical and agricultural setting. It also identifies the challenges that must be overcome in order to develop AFPs into therapeutics.

真菌在环境中无处不在,在营养物质的分解和循环中发挥着关键作用。一方面,真菌的特殊属性是农业和工业部门的巨大财富,因为它们被用作营养源、酶、色素、调味剂和生物控制剂的生产者,以及食品加工、生物修复和植物生长促进剂。另一方面,它们也对我们的生活和环境提出了严峻的挑战,因为它们是植物、动物和人类真菌感染的罪魁祸首。虽然宿主免疫力能抵御病原体的入侵,但某些因素却有利于真菌疾病的发生。真菌感染的发病率呈上升趋势,真菌病原体对已批准药物的抗药性也在惊人地增加。抗真菌药物的数量有限、患者对抗真菌药物的耐受性差导致新药开发遇到障碍、独特的抗真菌靶点数量有限以及物种特异性低,这些因素导致抗真菌药物管线逐渐枯竭,新发现的抗真菌药物十分罕见。有希望成为下一代治疗药物的候选药物是抗微生物蛋白和肽(AMPs),这些蛋白和肽由属于所有生物界的众多原核和真核生物产生。重要的是,欧洲真菌纲的丝状真菌已被证明是具有特殊抗真菌活性的 AMPs 的丰富来源。越来越多的已发表研究反映了人们在寻找新的抗真菌蛋白和肽(AFPs)、其功效、物种特异性和适用性方面所做的努力。在这篇综述中,我们将讨论与真菌有关的重要方面、真菌对我们生活的影响以及治疗植物、动物和人类真菌感染所涉及的问题。我们特别强调了欧罗巴菌中的 AFPs 作为有前途的替代抗真菌疗法的潜力。这篇文章深入探讨了其结构特征、作用模式以及在临床和农业环境中的潜在应用进展。文章还指出了将 AFPs 开发成治疗药物必须克服的挑战。
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引用次数: 0
Mycorrhizal inoculation and fertilizer microdosing interactions in pearl millet (Pennisetum glaucum) under greenhouse conditions. 温室条件下珍珠粟(Pennisetum glaucum)菌根接种与肥料微剂量的相互作用。
IF 2.1 Q3 MYCOLOGY Pub Date : 2024-08-29 eCollection Date: 2024-01-01 DOI: 10.3389/ffunb.2024.1448156
Malick Ndiaye, Alain Mollier, Adama Diouf, Tahir Abdoulaye Diop

Introduction: Soil fertility is a major constraint to agricultural development in the Sahel region of Africa. One alternative to reducing the use of mineral fertilizers is to partially replace them with microbes that promote nutrition and growth, such as arbuscular mycorrhizal fungi (AMF). Mineral fertilizer microdosing is a technique developed to enhance fertilizer efficiency and encourage smallholder farmers to adopt higher mineral fertilizer applications.

Methods: A pot experiment was set up to study the effects of AMF inoculation on the mineral nutrition of pearl millet under mineral fertilizer microdosing conditions. The experimental setup followed a randomized complete block design with five replicates. The treatments tested on millet were an absolute control and eight microdoses derived from the combination of three doses of 15- 10-10 [nitrogen, phosphorus, and potassium (NPK)] mineral fertilizer (2 g, 3 g, and 5 g per pot), three doses of urea (1 g, 2 g, and 3 g per pot), and three doses of organic manure (OM) (200 g, 400 g, and 600 g), combined with and without AMF (Rhizophagus irregularis and Rhizophagus aggregatum). The parameters studied were growth, root colonization by AMF, and mineral nutrition. Plant height, stem diameter, root dry biomass, and percentage of root mycorrhization were measured.

Results and discussion: The results revealed a significant effect of the fertilizers on the growth of pearl millet compared to the control. AMF and OM treatments resulted in the highest biomass production. AMF combined with microdoses of NPK improved N and calcium (Ca) concentrations, while their combination with organic matter mainly improved the K concentration. Combining AMF with microdosed NPK and compost enhanced zinc (Zn) and nickel (Ni) concentrations. Root colonization varied from 0.55 to 56.4%. This investigation highlights the positive effects of AMF inoculation on nutrient uptake efficiency when combined with microdosing fertilization.

导言:土壤肥力是非洲萨赫勒地区农业发展的主要制约因素。减少使用矿物肥料的一个替代方法是用促进营养和生长的微生物(如丛生菌根真菌)部分替代矿物肥料。矿物肥料微量施用是为提高肥料效率和鼓励小农户提高矿物肥料施用量而开发的一种技术:方法:通过盆栽实验研究在微量矿物质肥料条件下接种 AMF 对珍珠粟矿物质营养的影响。实验设置采用随机完全区组设计,共设五个重复。对小米进行的试验处理包括绝对对照和八种微剂量,分别来自三种剂量的 15- 10-10 [氮、磷、钾(NPK)]矿物肥料(每盆 2 克、3 克和 5 克)、三种剂量的尿素(每盆 1 克、2 克和 3 克)以及三种剂量的有机肥(200 克、400 克和 600 克),并结合和不结合 AMF(Rhizophagus irregularis 和 Rhizophagus aggregatum)。研究参数包括生长、AMF 的根定植和矿物质营养。测量了植株高度、茎直径、根干生物量和根菌根化百分比:结果表明,与对照相比,肥料对珍珠粟的生长有明显影响。AMF和OM处理产生的生物量最高。AMF与微量氮磷钾的结合提高了氮和钙的浓度,而与有机质的结合主要提高了钾的浓度。将 AMF 与微量氮磷钾和堆肥结合使用可提高锌(Zn)和镍(Ni)的浓度。根定植率从 0.55% 到 56.4% 不等。这项调查突出表明,AMF 接种与微量施肥相结合对养分吸收效率有积极影响。
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引用次数: 0
Corrigendum: The Sordariomycetes: an expanding resource with Big Data for mining in evolutionary genomics and transcriptomics. 更正:鞭毛霉菌纲:用于挖掘进化基因组学和转录组学大数据的不断扩大的资源。
IF 2.1 Q3 MYCOLOGY Pub Date : 2024-08-20 eCollection Date: 2024-01-01 DOI: 10.3389/ffunb.2024.1478516
Zheng Wang, Wonyong Kim, Yen-Wen Wang, Elizabeta Yakubovich, Caihong Dong, Frances Trail, Jeffrey P Townsend, Oded Yarden

[This corrects the article DOI: 10.3389/ffunb.2023.1214537.].

[此处更正了文章 DOI:10.3389/ffunb.2023.1214537]。
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引用次数: 0
Dual-RNA-sequencing to elucidate the interactions between sorghum and Colletotrichum sublineola. 通过双 RNA 测序阐明高粱与 Colletotrichum sublineola 之间的相互作用。
IF 2.1 Q3 MYCOLOGY Pub Date : 2024-08-16 eCollection Date: 2024-01-01 DOI: 10.3389/ffunb.2024.1437344
Saddie Vela, Emily S A Wolf, Jeffrey A Rollins, Hugo E Cuevas, Wilfred Vermerris

In warm and humid regions, the productivity of sorghum is significantly limited by the fungal hemibiotrophic pathogen Colletotrichum sublineola, the causal agent of anthracnose, a problematic disease of sorghum (Sorghum bicolor (L.) Moench) that can result in grain and biomass yield losses of up to 50%. Despite available genomic resources of both the host and fungal pathogen, the molecular basis of sorghum-C. sublineola interactions are poorly understood. By employing a dual-RNA sequencing approach, the molecular crosstalk between sorghum and C. sublineola can be elucidated. In this study, we examined the transcriptomes of four resistant sorghum accessions from the sorghum association panel (SAP) at varying time points post-infection with C. sublineola. Approximately 0.3% and 93% of the reads mapped to the genomes of C. sublineola and Sorghum bicolor, respectively. Expression profiling of in vitro versus in planta C. sublineola at 1-, 3-, and 5-days post-infection (dpi) indicated that genes encoding secreted candidate effectors, carbohydrate-active enzymes (CAZymes), and membrane transporters increased in expression during the transition from the biotrophic to the necrotrophic phase (3 dpi). The hallmark of the pathogen-associated molecular pattern (PAMP)-triggered immunity in sorghum includes the production of reactive oxygen species (ROS) and phytoalexins. The majority of effector candidates secreted by C. sublineola were predicted to be localized in the host apoplast, where they could interfere with the PAMP-triggered immunity response, specifically in the host ROS signaling pathway. The genes encoding critical molecular factors influencing pathogenicity identified in this study are a useful resource for subsequent genetic experiments aimed at validating their contributions to pathogen virulence. This comprehensive study not only provides a better understanding of the biology of C. sublineola but also supports the long-term goal of developing resistant sorghum cultivars.

炭疽病是高粱(Sorghum bicolor (L.) Moench)的一种严重病害,可导致粮食和生物量减产高达 50%。尽管宿主和真菌病原体都有基因组资源,但人们对高粱-C. sublineola 相互作用的分子基础知之甚少。通过采用双 RNA 测序方法,可以阐明高粱与亚线虫之间的分子串扰。在本研究中,我们研究了高粱协会(SAP)中四个抗性高粱品种在感染亚线虫后不同时间点的转录组。大约 0.3% 和 93% 的读数分别映射到亚线虫和双色高粱的基因组。感染后 1 天、3 天和 5 天(dpi)亚线虫体外与植物体内的表达谱分析表明,在从生物营养阶段向坏死阶段过渡期间(3 dpi),编码分泌型候选效应物、碳水化合物活性酶(CAZymes)和膜转运体的基因表达量增加。病原体相关分子模式(PAMP)触发的高粱免疫特征包括活性氧(ROS)和植物毒素的产生。据预测,亚线虫分泌的候选效应物大多定位于宿主的细胞外质,它们可能干扰 PAMP 触发的免疫反应,特别是宿主的 ROS 信号通路。本研究中发现的编码影响致病性的关键分子因子的基因为后续遗传实验提供了有用的资源,这些实验旨在验证这些基因对病原体毒力的贡献。这项全面的研究不仅有助于更好地了解亚线虫的生物学特性,还有助于实现开发抗性高粱栽培品种的长期目标。
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引用次数: 0
Phosphate availability conditions caspofungin tolerance, capsule attachment and titan cell formation in Cryptococcus neoformans. 磷酸盐的可用性决定了新生隐球菌对卡泊芬净的耐受性、菌盖附着和泰坦细胞的形成。
IF 2.1 Q3 MYCOLOGY Pub Date : 2024-08-14 eCollection Date: 2024-01-01 DOI: 10.3389/ffunb.2024.1447588
Xianya Qu, Kabir Bhalla, Linda C Horianopoulos, Guanggan Hu, Armando Alcázar Magaña, Leonard J Foster, Leandro Buffoni Roque da Silva, Matthias Kretschmer, James W Kronstad

There is an urgent need for new antifungal drugs to treat invasive fungal diseases. Unfortunately, the echinocandin drugs that are fungicidal against other important fungal pathogens are ineffective against Cryptococcus neoformans, the causative agent of life-threatening meningoencephalitis in immunocompromised people. Contributing mechanisms for echinocandin tolerance are emerging with connections to calcineurin signaling, the cell wall, and membrane composition. In this context, we discovered that a defect in phosphate uptake impairs the tolerance of C. neoformans to the echinocandin caspofungin. Our previous analysis of mutants lacking three high affinity phosphate transporters revealed reduced elaboration of the polysaccharide capsule and attenuated virulence in mice. We investigated the underlying mechanisms and found that loss of the transporters and altered phosphate availability influences the cell wall and membrane composition. These changes contribute to the shedding of capsule polysaccharide thus explaining the reduced size of capsules on mutants lacking the phosphate transporters. We also found an influence of the calcineurin pathway including calcium sensitivity and an involvement of the endoplasmic reticulum in the response to phosphate limitation. Furthermore, we identified membrane and lipid composition changes consistent with the role of phosphate in phospholipid biosynthesis and with previous studies implicating membrane integrity in caspofungin tolerance. Finally, we discovered a contribution of phosphate to titan cell formation, a cell type that displays modified cell wall and capsule composition. Overall, our analysis reinforces the importance of phosphate as a regulator of cell wall and membrane composition with implications for capsule attachment and antifungal drug susceptibility.

治疗侵袭性真菌疾病急需新的抗真菌药物。遗憾的是,对其他重要真菌病原体具有杀真菌作用的棘白菌素类药物对新隐球菌无效,而新隐球菌是导致免疫力低下人群患上脑膜脑炎并危及生命的病原体。导致棘球蚴耐受性的机制正在出现,这些机制与钙调素信号、细胞壁和膜组成有关。在这种情况下,我们发现磷酸盐摄取的缺陷会影响新变形杆菌对棘白菌素类药物卡泊芬净的耐受性。我们之前对缺乏三种高亲和力磷酸盐转运体的突变体进行了分析,结果发现小鼠体内多糖胶囊的合成减少,毒力减弱。我们对其潜在机制进行了研究,发现转运体的缺失和磷酸盐供应的改变会影响细胞壁和膜的组成。这些变化有助于胶囊多糖的脱落,从而解释了缺乏磷酸盐转运体的突变体胶囊大小减小的原因。我们还发现了钙调磷酸酶通路的影响,包括钙敏感性和内质网对磷酸盐限制反应的参与。此外,我们还发现了膜和脂质成分的变化,这与磷酸盐在磷脂生物合成中的作用以及之前关于膜完整性与卡泊芬净耐受性有关的研究相一致。最后,我们发现了磷酸盐对钛细胞形成的作用,这种细胞类型的细胞壁和囊的组成发生了改变。总之,我们的分析加强了磷酸盐作为细胞壁和膜组成调节剂的重要性,并对胶囊附着和抗真菌药物敏感性产生了影响。
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Frontiers in fungal biology
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