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Quantitative MRI of a Cerebral Cryptococcoma Mouse Model for In Vivo Distinction between Different Cryptococcal Molecular Types. 用于体内区分不同隐球菌分子类型的脑隐球菌瘤小鼠模型的定量 MRI。
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-08-22 DOI: 10.3390/jof10080593
Luigi Musetta, Shannon Helsper, Lara Roosen, Dries Maes, Anca Croitor Sava, Liesbeth Vanherp, Willy Gsell, Greetje Vande Velde, Katrien Lagrou, Wieland Meyer, Uwe Himmelreich

The controversially discussed taxonomy of the Cryptococcus neoformans/Cryptococcus gattii species complex encompasses at least eight major molecular types. Cerebral cryptococcomas are a common manifestation of cryptococcal neurological disease. In this study, we compared neurotypical symptoms and differential neurovirulence induced by one representative isolate for each of the eight molecular types studied. We compared single focal lesions caused by the different isolates and evaluated the potential relationships between the fungal burden and properties obtained with quantitative magnetic resonance imaging (qMRI) techniques such as diffusion MRI, T2 relaxometry and magnetic resonance spectroscopy (MRS). We observed an inverse correlation between parametric data and lesion density, and we were able to monitor longitudinally biophysical properties of cryptococcomas induced by different molecular types. Because the MRI/MRS techniques are also clinically available, the same approach could be used to assess image-based biophysical properties that correlate with fungal cell density in lesions in patients to determine personalized treatments.

新变形隐球菌/加特氏隐球菌复合菌种的分类讨论颇具争议,至少包括八种主要的分子类型。脑隐球菌瘤是隐球菌神经系统疾病的常见表现。在这项研究中,我们比较了所研究的八种分子类型中每种类型的一个代表性分离株所诱发的神经典型症状和不同的神经感染性。我们比较了由不同分离株引起的单个病灶,并评估了真菌负担与定量磁共振成像(qMRI)技术(如弥散磁共振成像、T2弛豫测定和磁共振波谱成像(MRS))获得的特性之间的潜在关系。我们观察到参数数据与病变密度之间存在反相关性,而且我们能够纵向监测不同分子类型诱发的隐球菌瘤的生物物理特性。由于 MRI/MRS 技术也可用于临床,因此同样的方法可用于评估患者病灶中与真菌细胞密度相关的基于图像的生物物理特性,从而确定个性化的治疗方法。
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引用次数: 0
Antifungal Activity of Cyperus articulatus, Cyperus rotundus and Lippia alba Essential Oils against Aspergillus flavus Isolated from Peanut Seeds. 香柏、香附和白花梨精油对从花生种子中分离出的黄曲霉的抗真菌活性
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-08-21 DOI: 10.3390/jof10080591
Safietou Sabaly, Yoro Tine, Alioune Diallo, Abdoulaye Faye, Mouhamed Cisse, Abdoulaye Ndiaye, Cebastiana Sambou, Cheikhouna Gaye, Alassane Wele, Julien Paolini, Jean Costa, Aboubacry Kane, Saliou Ngom

Aspergillus flavus is a cosmopolitan saprophytic fungus that infests several foodstuffs and is associated with adverse effects in humans. In Senegal, significant losses of groundnut production are mainly due to contamination caused by this species. This study evaluated in vitro antifungal activities of Cyperus articulatus, Cyperus rotundus and Lippia alba essential oils against A. flavus isolated from peanut seeds. Essential oils obtained by hydrodistillation of rhizomes of the two Cyperus species and leaves of L. alba were analyzed with GC-DIF and GC-MS. The essential oil yields from C. articulatus, C. rotundus and L. alba were 1.1%, 1.3% and 1.7%, respectively. These three samples had the following chemotypes: (i) mustakone (21.4%)/eudesma-4(15)-7-dien-1β-ol (8.8%)/caryophyllene oxide (5.9%), (ii) caryophyllene oxide (25.2%)/humulene epoxyde 2 (35.0%) and (iii) geranial (46.6%)/neral (34.6%). The three oils tested inhibited the growth of A. flavus at concentrations between 100 and 1000 ppm. The L. alba oil was the most effective with total clearance of A. flavus on PDA. For the essential oils of C. rotundus (93.65%) and C. articulatus (78.11%), the highest inhibition rates were obtained with a 1000 ppm dose. Thus, L. alba oil could be used safely as an effective protector of groundnuts against A. flavus.

黄曲霉菌(Aspergillus flavus)是一种世界性隐性真菌,可侵染多种食品,并对人体产生不良影响。在塞内加尔,花生生产的重大损失主要是由这种真菌造成的。这项研究评估了香附、腐叶香附和白花栗精油对从花生种子中分离出的黄曲霉菌的体外抗真菌活性。采用 GC-DIF 和 GC-MS 分析了通过水蒸馏法获得的两种香附根茎和白叶李的精油。C. articulatus、C. rotundus 和 L. alba 的精油产量分别为 1.1%、1.3% 和 1.7%。这三种样本的化学类型如下:(i) 芥子酮(21.4%)/桉叶-4(15)-7-二烯-1β-醇(8.8%)/氧化香叶烯(5.9%),(ii) 氧化香叶烯(25.2%)/环氧胡柚烯 2(35.0%)和(iii) 香叶醇(46.6%)/香叶(34.6%)。在 100 至 1000 ppm 的浓度范围内,测试的三种精油都能抑制黄曲霉的生长。L. alba 精油对完全清除 PDA 上的黄曲霉最为有效。对于 C. rotundus(93.65%)和 C. articulatus(78.11%)精油,1000 ppm 剂量的抑制率最高。因此,L. alba 精油可以作为一种有效的保护花生免受黄曲霉侵害的安全用油。
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引用次数: 0
A Fusarium verticillioides MAT1-2 Strain near Isogenic to the Sequenced FGSC7600 Strain for Producing Homozygous Multigene Mutants. 疣状镰刀菌 MAT1-2 株系与已测序的 FGSC7600 株系接近同源,可产生同源多基因突变体。
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-08-21 DOI: 10.3390/jof10080592
Scott E Gold, Daren W Brown, Felicia N Williams, Brian D Nadon, Vivian T Vo, Christine E Miller

Fungal genetic systems ideally combine molecular tools for genome manipulation and a sexual reproduction system to create an informative assortment of combinations of genomic modifications. When employing the sexual cycle to generate multi-mutants, the background genotype variations in the parents may result in progeny phenotypic variation obscuring the effects of combined mutations. Here, to mitigate this variation in Fusarium verticillioides, we generated a MAT1-2 strain that was near isogenic to the sequenced wild-type MAT1-1 strain, FGSC7600. This was accomplished by crossing FGSC7600 with the divergent wild-type MAT1-2 strain FGSC7603 followed by six sequential backcrosses (e.g., six generations) of MAT1-2 progeny to FGSC7600. We sequenced each generation and mapped recombination events. The parental cross involved twenty-six crossovers on nine of the eleven chromosomes. The dispensable chromosome 12, found in FGSC7603 but lacking in FGSC7600, was not present in the progeny post generation five. Inheritance of complete chromosomes without crossover was frequently observed. A deletion of approximately 140 kilobases, containing 54 predicted genes on chromosome 4, occurred in generation 4 and was retained in generation 5 indicating that these genes are dispensable for growth and both asexual and sexual reproduction. The final MAT1-2 strain TMRU10/35 is about 93% identical to FGSC7600. TMRU10/35 is available from the Fungal Genetics Stock Center as FGSC27326 and from the ARS Culture Collection as NRRL64809.

真菌遗传系统将基因组操作的分子工具与有性生殖系统理想地结合在一起,创造出各种信息丰富的基因组修饰组合。当利用有性生殖周期产生多突变体时,亲本的背景基因型变异可能导致后代表型变异,从而掩盖了组合突变的效果。在此,为了减少轮纹镰刀菌中的这种变异,我们产生了一种与已测序的野生型 MAT1-1 株系 FGSC7600 接近同源的 MAT1-2 株系。具体方法是将 FGSC7600 与不同的野生型 MAT1-2 菌株 FGSC7603 杂交,然后将 MAT1-2 后代与 FGSC7600 连续回交六次(即六代)。我们对每一代都进行了测序,并绘制了重组事件图。亲本杂交涉及 11 条染色体中 9 条染色体上的 26 次交叉。在 FGSC7603 中发现而在 FGSC7600 中缺乏的第 12 号染色体在第五代后代中不存在。经常观察到完整染色体的遗传而没有交叉。第 4 代出现了约 140 千碱基的缺失,其中包含第 4 号染色体上的 54 个预测基因,第 5 代保留了这些基因,这表明这些基因对于生长以及无性和有性生殖都是不可或缺的。最终的 MAT1-2 菌株 TMRU10/35 与 FGSC7600 大约 93% 相同。TMRU10/35 可从真菌遗传资源中心(Fungal Genetics Stock Center)获得,编号为 FGSC27326;也可从美国农业部菌种保藏中心(ARS Culture Collection)获得,编号为 NRRL64809。
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引用次数: 0
Reduction in Ochratoxin A Occurrence in Coffee: From Good Practices to Biocontrol Agents. 降低咖啡中赭曲霉毒素 A 的含量:从良好操作到生物控制剂。
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-08-20 DOI: 10.3390/jof10080590
Claudia López-Rodríguez, Carol Verheecke-Vaessen, Caroline Strub, Angélique Fontana, Sabine Schorr-Galindo, Angel Medina

Ochratoxin A (OTA) is a mycotoxin mainly produced by Aspergillus section Circumdati and section Nigri across the coffee chain. OTA is nephrotoxic and is a threat to human health. This review summarizes current knowledge on how to reduce OTA concentration in coffee from farm to cup. After a brief introduction to the OTA occurrence in coffee, current good management practices are introduced. The core of this review focuses on biocontrol and microbial decontamination by lactic acid bacteria, yeasts and fungi, and their associated enzymes currently reported in the literature. Special attention is given to publications closest to in vivo applications of biocontrol agents and microbial OTA adsorption or degradation agents. Finally, this review provides an opinion on which future techniques to promote within the coffee supply chain.

赭曲霉毒素 A(OTA)是一种霉菌毒素,主要由整个咖啡链中的圆环曲霉和尼格里曲霉产生。OTA 具有肾毒性,对人类健康构成威胁。本综述总结了目前关于如何降低从农场到咖啡杯中的 OTA 浓度的知识。在简要介绍了咖啡中的 OTA 发生情况后,介绍了当前的良好管理实践。本综述的核心内容侧重于目前文献中报道的乳酸菌、酵母菌和真菌及其相关酶的生物控制和微生物净化。特别关注了与生物控制剂和微生物 OTA 吸附或降解剂的体内应用最接近的出版物。最后,本综述就未来在咖啡供应链中推广哪些技术提出了意见。
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引用次数: 0
Six Species of Phyllachora with Three New Taxa on Grass from Sichuan Province, China. 中国四川省草地上的 6 种 Phyllachora 和 3 个新分类群。
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-08-19 DOI: 10.3390/jof10080588
Qi-Rong Sun, Xiu-Lan Xu, Zhen Zeng, Yu Deng, Feng Liu, Li-Ping Gao, Fei-Hu Wang, Ya-Qian Yan, Ying-Gao Liu, Chun-Lin Yang

Phyllachora (Phyllachoraceae, Phyllachorales) species are parasitic fungi with a wide global distribution, causing tar spots on plants. In this study, we describe three newly discovered species: Phyllachora chongzhouensis, Phyllachora neidongensis, and Phyllachora huiliensis from Poaceae in China. These species were characterized using morphological traits and multi-locus phylogeny based on the internal transcribed spacer region (ITS) with the intervening 5.8S rRNA gene, the large subunit of the rRNA gene (LSU), and the 18S ribosomal RNA gene (SSU). Three known species of P. chloridis, P. graminis, and P. miscanthi have also been redescribed, because, in reviewing the original references of P. chloridis, P. graminis, and P. miscanthi, these were found to be relatively old and in Chinese or abbreviated. In addition, the illustrations were simple. In molecular identification, the ITS sequence is short, while the ITS, LSU, and SSU are incomplete. Therefore, this study provides new important references for the redescription of three known species and provides further evidence for the identification of new taxa.

Phyllachora(Phyllachoraceae,Phyllachorales)属真菌是一种寄生真菌,在全球广泛分布,可引起植物上的焦油斑。在这项研究中,我们描述了三个新发现的物种:Phyllachora chongzhouensis、Phyllachora neidongensis 和 Phyllachora huiliensis。通过形态学特征和基于内部转录间隔区(ITS)与中间的 5.8S rRNA 基因、rRNA 基因大亚基(LSU)和 18S 核糖体 RNA 基因(SSU)的多焦点系统进化对这些物种进行了鉴定。由于在查阅 P. chloridis、P. graminis 和 P. miscanthi 的原始参考文献时,发现这些文献相对较老,且为中文或缩写,因此还重新描述了 P.loridis、P. graminis 和 P. miscanthi 的三个已知种。此外,插图也比较简单。在分子鉴定方面,ITS 序列较短,ITS、LSU 和 SSU 不完整。因此,本研究为三个已知种的重新描述提供了新的重要参考文献,并为新类群的鉴定提供了进一步的证据。
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引用次数: 0
Morphological and Phylogenetic Analyses Reveal Three Novel Species of Sanguinoderma (Ganodermataceae, Basidiomycota) from Yunnan Province, China. 形态学和系统发育分析揭示了中国云南省的三个 Sanguinoderma (Ganodermataceae,担子菌纲)新种。
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-08-19 DOI: 10.3390/jof10080589
Kai-Yang Niu, Jun He, Song-Ming Tang, Xi-Jun Su, Zong-Long Luo

Sanguinoderma (Ganodermataceae) is recognized as a valuable medicinal resource in Taiwan, China. Additionally, it serves as a traditional folk medicine for treating neurotic epilepsy in Malaysia. This study involved the collection of six specimens of Sanguinoderma from Yunnan Province, China. Employing multigene phylogenetic analysis of DNA sequences, including internal transcribed spacer (ITS), nuclear large subunit (LSU), RNA polymerase II second largest subunit (rpb2), translation elongation factor 1-alpha (tef1-α), mitochondrial small subunit (mtSSU), nuclear small subunit (nSSU) and morphological examinations, three new species, viz. Sanguinoderma concentricum, S. dehongense and S. ovisporum, are introduced. Sanguinoderma concentricum is characterized by a central stipe basidiomata, an orbicular to suborbicular pileus, a grayish-yellow surface with alternating concentric zones and wavy margin-like petals and regular pileipellis cells (4-8 × 17-28 μm). Sanguinoderma dehongense is characterized by a long stipe and flabelliform basidiomata, a dark-grayish yellow-to-dark-yellow pileus surface, irregular pileipellis cells and wavy margin and ellipsoid basidia (8-11 × 9-13 μm). Sanguinoderma ovisporum is characterized by a reniform basidiomata, a heterogeneous context and ovoid basidiospores (7.5-8.6 × 5.5-7.2 µm). A detailed description and illustrations of these new species are provided, as well as a morphological comparison with similar taxa.

在中国台湾,三棱皮(Ganodermataceae)被认为是一种珍贵的药用资源。此外,它还是马来西亚治疗神经性癫痫的传统民间药物。本研究从中国云南省采集了六份灵芝标本。通过对DNA序列(包括内部转录间隔序列(ITS)、核大亚基序列(LSU)、RNA聚合酶II第二大亚基序列(rpb2)、翻译延伸因子1-α序列(tef1-α)、线粒体小亚基序列(mtSSU)、核小亚基序列(nSSU))进行多基因系统发育分析和形态学检查,发现了三个新种,即:同心圆灵芝属(Sanguinoderma concentrica)、褐藻灵芝属(Sanguinoderma concentrica)和褐藻灵芝属(Sanguinoderma concentrica)。S. dehongense 和 S. ovisporum。Sanguinoderma concentricum 的特征是中央有一个柄基瘤,绒毛呈圆形至近圆形,表面呈灰黄色,有交替的同心区和波浪状边缘花瓣,绒毛细胞规则(4-8 × 17-28 μm)。Sanguinoderma dehongense 的特征是有长柄和扇形基瘤,绒毛表面呈深灰色黄至深黄色,绒毛细胞不规则,边缘呈波浪状,基瘤呈椭圆形(8-11 × 9-13 μm)。Sanguinoderma ovisporum 的特征是具有肾形基殖体、异质背景和卵圆形基殖体(7.5-8.6 × 5.5-7.2 μm)。本文提供了这些新种的详细描述和插图,以及与类似类群的形态比较。
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引用次数: 0
Differential Strategies of Ectomycorrhizal Development between Suillus luteus and Pinus massoniana in Response to Nutrient Changes. 黄叶杉(Suillus luteus)和麻栎(Pinus massoniana)的外生菌根发育对养分变化的响应策略存在差异。
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-08-19 DOI: 10.3390/jof10080587
Xueyu Pan, Junfeng Liang, Jinhua Zhang, Yan Zhao, Mingjie Chen

Ectomycorrhizal fungi employ different strategies for mycelial growth and host colonization under varying nutrient conditions. However, key genes associated with mycorrhizal interaction should be influenced solely by the inoculation treatment and not by nutrient variations. To utilize subtle nutrient differences and rapidly screen for key genes related to the interaction between Suillus luteus and Pinus massoniana, we performed an inoculation experiment using culture bottles containing high- and low-nutrient media. Interestingly, S. luteus LS88 promoted the growth of P. massoniana seedlings without mature ectomycorrhiza, and the impact of LS88 inoculation on P. massoniana roots was greater than that of nutrient changes. In this study, the resequenced genome of the LS88 strain was utilized for transcriptome analysis of the strain. The analysis indicated that a unique gene encoding glutathione S-transferase (GST) in LS88 is likely involved in colonizing P. massoniana roots. In this study, the GST gene expression was independent of nutrient levels. It was probably induced by P. massoniana and could be used as a marker for S. luteus colonization degree.

在不同的营养条件下,外生菌根真菌采用不同的菌丝生长和宿主定殖策略。然而,与菌根相互作用相关的关键基因应该只受接种处理的影响,而不受养分变化的影响。为了利用微妙的养分差异,快速筛选出与黄叶水霉菌(Suillus luteus)和马尾松(Pinus massoniana)之间相互作用相关的关键基因,我们使用装有高养分和低养分培养基的培养瓶进行了接种实验。有趣的是,S. luteus LS88能促进没有成熟外生菌根的P. massoniana幼苗的生长,而且LS88接种对P. massoniana根系的影响大于营养变化的影响。本研究利用重新测序的 LS88 菌株基因组对该菌株进行了转录组分析。分析表明,LS88 菌株中编码谷胱甘肽 S-转移酶(GST)的独特基因可能参与了 P. massoniana 根系的定殖。在这项研究中,GST 基因的表达与营养水平无关。它可能是由 P. massoniana 诱导的,可用作黄体球菌定殖程度的标记。
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引用次数: 0
The Expanding Mycovirome of Aspergilli. 曲霉菌不断扩大的霉菌群
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-08-17 DOI: 10.3390/jof10080585
Josephine L Battersby, David A Stevens, Robert H A Coutts, Vladimír Havlíček, Joe L Hsu, Gabriele Sass, Ioly Kotta-Loizou

Mycoviruses are viruses that infect fungi and are widespread across all major fungal taxa, exhibiting great biological diversity. Since their discovery in the 1960s, researchers have observed a myriad of fungal phenotypes altered due to mycoviral infection. In this review, we examine the nuanced world of mycoviruses in the context of the medically and agriculturally important fungal genus, Aspergillus. The advent of RNA sequencing has revealed a previous underestimate of viral prevalence in fungi, in particular linear single-stranded RNA viruses, and here we outline the diverse viral families known to date that contain mycoviruses infecting Aspergillus. Furthermore, we describe these novel mycoviruses, highlighting those with peculiar genome structures, such as a split RNA dependent RNA polymerase gene. Next, we delineate notable mycovirus-mediated phenotypes in Aspergillus, in particular reporting on observations of mycoviruses that affect their fungal host's virulence and explore how this may relate to virus-mediated decreased stress tolerance. Furthermore, mycovirus effects on microbial competition and antifungal resistance are discussed. The factors that influence the manifestation of these phenotypes, such as temperature, fungal life stage, and infection with multiple viruses, among others, are also evaluated. In addition, we attempt to elucidate the molecular mechanisms that underpin these phenotypes, examining how mycoviruses can be targets, triggers, and even suppressors of RNA silencing and how this can affect fungal gene expression and phenotypes. Finally, we highlight the potential therapeutic applications of mycoviruses and how, in an approach analogous to bacteriophage therapy, their ability to produce hypovirulence in Aspergillus might be used to attenuate invasive aspergillosis infections in humans.

霉菌病毒是一种感染真菌的病毒,广泛存在于所有主要的真菌类群中,表现出极大的生物多样性。自 20 世纪 60 年代发现霉菌病毒以来,研究人员已经观察到无数真菌表型因霉菌病毒感染而发生改变。在这篇综述中,我们以在医学和农业上具有重要意义的曲霉属真菌为背景,探讨了真菌病毒的微妙世界。RNA 测序技术的出现揭示了以前低估的真菌中的病毒流行率,尤其是线性单链 RNA 病毒,在此我们概述了迄今已知的包含感染曲霉菌的霉菌病毒的各种病毒家族。此外,我们还描述了这些新型霉菌病毒,重点介绍了那些基因组结构奇特的病毒,如分裂的 RNA 依赖性 RNA 聚合酶基因。接下来,我们描述了曲霉菌中由霉菌病毒介导的显著表型,特别报告了对影响其真菌宿主毒力的霉菌病毒的观察结果,并探讨了这可能与病毒介导的应激耐受性降低之间的关系。此外,还讨论了霉菌病毒对微生物竞争和抗真菌抗性的影响。我们还评估了影响这些表型表现的因素,如温度、真菌生命阶段和感染多种病毒等。此外,我们还试图阐明支撑这些表型的分子机制,研究霉菌病毒如何成为 RNA 沉默的靶标、触发器甚至抑制器,以及这如何影响真菌基因表达和表型。最后,我们强调了霉菌病毒的潜在治疗应用,以及如何通过类似于噬菌体疗法的方法,利用霉菌病毒在曲霉菌中产生低病毒性的能力来减轻人类的侵袭性曲霉菌病感染。
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引用次数: 0
Mechanisms and Virulence Factors of Cryptococcus neoformans Dissemination to the Central Nervous System. 新型隐球菌向中枢神经系统扩散的机制和致病因素。
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-08-17 DOI: 10.3390/jof10080586
Ammar Mutahar Al-Huthaifi, Bakeel A Radman, Abdullah Ali Al-Alawi, Fawad Mahmood, Tong-Bao Liu

Cryptococcosis is a prevalent fungal infection of the central nervous system (CNS) caused by Cryptococcus neoformans, a yeast with a polysaccharide capsule in the basidiomycete group. Normally, C. neoformans infects the respiratory tract and then breaches the blood-brain barrier (BBB), leading to meningitis or meningoencephalitis, which leads to hundreds of thousands of deaths each year. Although the mechanism by which C. neoformans infiltrates the BBB to invade the brain has yet to be fully understood, research has revealed that C. neoformans can cross the BBB using transcellular penetration, paracellular traversal, and infected phagocytes (the "Trojan horse" mechanism). The secretion of multiple virulence factors by C. neoformans is crucial in facilitating the spread of infection after breaching the BBB and causing brain infections. Extensive research has shown that various virulence factors play a significant role in the dissemination of infection beyond the lungs. This review explores the mechanisms of C. neoformans entering the CNS and explains how it bypasses the BBB. Additionally, it aims to understand the interplay between the regulatory mechanisms and virulence factors of C. neoformans.

隐球菌病是中枢神经系统(CNS)的一种流行性真菌感染,由新形隐球菌引起,新形隐球菌是一种基枝孢霉属多糖囊酵母菌。通常,新生隐球菌会感染呼吸道,然后突破血脑屏障(BBB),引发脑膜炎或脑膜脑炎,每年导致数十万人死亡。虽然新形酵母菌渗入 BBB 入侵大脑的机制尚未完全清楚,但研究发现,新形酵母菌可通过跨细胞渗透、旁细胞穿越和受感染的吞噬细胞("特洛伊木马 "机制)穿过 BBB。新酵母菌分泌多种毒力因子,这对突破 BBB 后促进感染扩散并造成脑部感染至关重要。大量研究表明,各种毒力因子在肺部以外的感染传播中发挥着重要作用。本综述探讨了新变形杆菌进入中枢神经系统的机制,并解释了它是如何绕过 BBB 的。此外,这篇综述还旨在了解新变形杆菌的调控机制和毒力因子之间的相互作用。
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引用次数: 0
Atypical Presentation of Invasive Aspergillosis during Treatment with Mogamulizumab. 莫干单抗治疗期间侵袭性曲霉菌病的非典型表现
IF 4.2 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-08-17 DOI: 10.3390/jof10080584
Paolo Pavone, Laura Arletti, Fiorella Ilariucci, Tommaso Albano, Deborah Lusetti, Romina Corsini, Francesco Merli, Sergio Mezzadri

Treatment with CCR-4 antagonists has been shown to be protective against the development of invasive pulmonary aspergillosis in animal models. Herein, we present a case of fatal invasive pulmonary aspergillosis in a patient receiving Mogamulizumab. A 64-year-old man with refractory mycosis fungoides was found to have diffuse bilateral pulmonary nodules during a chest CT in June 2022. Bronchoalveolar lavage (BAL) fungal and bacterial cultures and galactomannan were negative, as well as serum beta-glucan and galactomannan. Histology showed a lymphoid infiltrate with a negative fungal stain, so a presumptive diagnosis of lymphoma infiltration was made, and the patient started the CCR-4 antagonist Mogamulizumab treatment in August 2022. He had no symptoms until November when he presented to the hematology clinic reporting dyspnea. He had neutrophilic leukocytosis (18.610 cells/µL), his c-reactive protein was 27 mg/dL, and his skin lesions from mycosis fungoides were just starting to improve. A CT scan showed large diffuse bilateral severely necrotic cavitated lesions with thick walls and apparently synchronous evolution. Beta-glucan was 31 pg/mL (wako method), while serum galactomannan 3.6. BAL was positive for Aspergillus fumigatus culture and galactomannan. Patient started voriconazole but, despite being in a stable condition, he suddenly died after two days. Discussion: Paradoxically, worsening of the chronic pulmonary aspergillosis has been reported after nivolumab treatment, and immune reconstitution syndromes are usually seen during neutrophil recovery after intensive chemotherapy. Our patient already presented indolent lung lesions from 5 months before and he remained completely asymptomatic until the aspergillosis diagnosis when he quickly passed away. Even if a progression of the lesions was expected in 5 months, this case had an atypical presentation. During the 5-month period, he had no pulmonary symptoms, and his c-reactive protein was negative. Furthermore, in the setting of the natural progression of subacute/chronic aspergillosis, a different radiological picture was expected with a less severe and probably asynchronous evolution. We think that the immune restoration associated with Mogamulizumab (also supported by the concurrent clinical response of the skin lesions) could have been detrimental in this case, exacerbating a catastrophic immune response or alternatively masquerading the clinical progression of aspergillosis. Clinicians should be aware of immune reconstitution syndromes possibly leading to fatal outcomes in immunocompromised patients starting CCR-4 antagonists.

在动物模型中,CCR-4拮抗剂对侵袭性肺曲霉菌病的发生具有保护作用。在此,我们介绍了一例接受莫干单抗治疗的致命侵袭性肺曲霉菌病病例。一名患有难治性真菌病的 64 岁男性患者于 2022 年 6 月做胸部 CT 时发现双侧肺部有弥漫性结节。支气管肺泡灌洗(BAL)真菌和细菌培养以及半乳甘露聚糖均为阴性,血清β-葡聚糖和半乳甘露聚糖也为阴性。组织学检查显示淋巴细胞浸润,真菌染色阴性,因此推断诊断为淋巴瘤浸润,患者于2022年8月开始接受CCR-4拮抗剂莫干单抗治疗。直到11月,他到血液科门诊报告呼吸困难时才出现症状。他的嗜中性白细胞增多(18.610 cells/μL),c反应蛋白为27 mg/dL,由真菌病引起的皮肤病变刚刚开始好转。CT 扫描显示,他的双侧大面积弥漫性严重坏死空洞化病灶壁很厚,且明显同步发展。β-葡聚糖为31 pg/mL(和光法),血清半乳甘露聚糖为3.6。BAL 真菌培养和半乳甘露聚糖检测均呈阳性。患者开始服用伏立康唑,尽管病情稳定,但两天后突然死亡。讨论矛盾的是,有报道称尼妥珠单抗治疗后慢性肺曲霉病恶化,而免疫重建综合征通常出现在强化化疗后中性粒细胞恢复期间。我们的患者在 5 个月前就已经出现了肺部惰性病变,并且一直完全没有症状,直到确诊为曲霉菌病后才很快去世。尽管预计病变会在 5 个月内发展,但这个病例的表现并不典型。在这 5 个月期间,他没有任何肺部症状,c 反应蛋白也呈阴性。此外,在亚急性/慢性曲霉菌病自然进展的情况下,预计会出现不同的放射学表现,病情较轻,可能是不同步的演变。我们认为,莫干单抗带来的免疫恢复(同时皮肤病变的临床反应也证明了这一点)在该病例中可能是有害的,它加剧了灾难性的免疫反应,或者掩盖了曲霉病的临床进展。临床医生应该意识到,免疫功能低下的患者在开始使用 CCR-4 拮抗剂时,免疫重建综合征可能会导致致命后果。
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Journal of Fungi
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