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Generational distribution of a Candida glabrata population: Resilient old cells prevail while younger cells dominate in the vulnerable host

机译：光滑念珠菌种群的世代分布：弹性老细胞占优势而较年轻的细胞在易感宿主中占主导地位

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Similar to other yeasts, the human pathogen Candida glabrata ages when it undergoes asymmetric, finite cell divisions, which determines its replicative lifespan. We sought to investigate if and how aging changes resilience of C. glabrata populations in the host environment. Our data demonstrate that old C. glabrata are more resistant to hydrogen peroxide and neutrophil killing, whereas young cells adhere better to epithelial cell layers. Consequently, virulence of old compared to younger C. glabrata cells is enhanced in the Galleria mellonella infection model. Electron microscopy images of old C. glabrata cells indicate a marked increase in cell wall thickness. Comparison of transcriptomes of old and young C. glabrata cells reveals differential regulation of ergosterol and Hog pathway associated genes as well as adhesion proteins, and suggests that aging is accompanied by remodeling of the fungal cell wall. Biochemical analysis supports this conclusion as older cells exhibit a qualitatively different lipid composition, leading to the observed increased emergence of fluconazole resistance when grown in the presence of fluconazole selection pressure. Older C. glabrata cells accumulate during murine and human infection, which is statistically unlikely without very strong selection. Therefore, we tested the hypothesis that neutrophils constitute the predominant selection pressure in vivo. When we altered experimentally the selection pressure by antibody-mediated removal of neutrophils, we observed a significantly younger pathogen population in mice. Mathematical modeling confirmed that differential selection of older cells is sufficient to cause the observed demographic shift in the fungal population. Hence our data support the concept that pathogenesis is affected by the generational age distribution of the infecting C. glabrata population in a host. We conclude that replicative aging constitutes an emerging trait, which is selected by the host and may even play an unanticipated role in the transition from a commensal to a pathogen state.

机译：与其他酵母相似，人类病原体光滑念珠菌会经历不对称的有限细胞分裂，从而决定其复制寿命。我们试图调查老化是否以及如何在寄主环境中改变无毛C. glabrata种群的弹性。我们的数据表明，老的光滑杯状梭菌对过氧化氢和中性粒细胞的杀灭能力更强，而年轻的细胞对上皮细胞层的粘附更好。因此，在Galleria mellonella感染模型中，与年轻的光滑毛状线虫细胞相比，老毒力得到增强。旧的光滑杯状梭菌细胞的电子显微镜图像表明细胞壁厚度显着增加。比较旧的和年轻的光滑杯状梭菌细胞的转录组，发现麦角固醇和Hog通路相关基因以及粘附蛋白的差异调节，并表明衰老伴随着真菌细胞壁的重塑。生化分析支持这一结论，因为较老的细胞表现出质的不同的脂质组成，导致在存在氟康唑选择压力的情况下生长时观察到的氟康唑耐药性增加。在鼠和人感染期间，较老的毛状线虫细胞会积聚，如果没有非常强的选择力，这在统计学上是不可能的。因此，我们测试了中性粒细胞构成体内主要选择压力的假设。当我们通过抗体介导的嗜中性粒细胞去除而通过实验改变选择压力时，我们观察到小鼠中的病原体种群明显年轻得多。数学模型证实，较老细胞的差异选择足以引起真菌种群中观察到的人口统计学变化。因此，我们的数据支持这样一个概念，即发病机理受宿主中感染的 glabrata 种群的世代年龄分布影响。我们得出结论，复制性衰老构成了一种新出现的特征，该特征由宿主选择，甚至可能在从共生状态向病原体状态的转变中起不可预期的作用。 展开▼

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期刊名称 PLoS Pathogens

作者
Tejas Bouklas; Luz Alonso-Crisóstomo; Tamás Székely Jr.; Elizabeth Diago-Navarro; Erika P. Orner; Kalie Smith; Mansa A. Munshi; Maurizio Del Poeta; Gábor Balázsi; Bettina C. Fries;
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年(卷),期 2017(13),5

年度 2017

页码 e1006355

总页数 27

原文格式 PDF

正文语种

中图分类微生物学;寄生动物、寄生虫学;医学寄生虫学;人体病毒学（致病病毒）;病毒（滤过性病毒）;

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专利

1. Generational distribution of a Candida glabrata population: Resilient old cells prevail, while younger cells dominate in the vulnerable host [J] . Tejas Bouklas, Luz Alonso-Crisóstomo, Tamás Székely Jr., PLoS Pathogens . 2017,第5期

机译：念珠菌种群的代理分布：有弹性的旧细胞占上风，而年轻人在脆弱的主机中占主导地位

2. Gain-of-Function Mutations in PDR1, a Regulator of Antifungal Drug Resistance in Candida glabrata, Control Adherence to Host Cells [J] . Luís Vale-Silva, Fran?oise Ischer, Salomé Leibundgut-Landmann, Infection and immunity . 2013,第5期

机译：功能获得性突变PDR1，光滑念珠菌中的抗真菌药物耐药性的调节剂，控制对宿主细胞的粘附。

3. De novo genome assembly of Candida glabrata Candida glabrata reveals cell wall protein complement and structure of dispersed tandem repeat arrays [J] . Xu Zhuwei, Green Brian, Benoit Nicole, Molecular Microbiology . 2020,第6期

机译：De Novo基因组组装Candida Glabrata Candida Glabrata揭示了细胞壁蛋白质补充和分散串联重复阵列的结构

4. Automatic Detection of Yeast and Pseudohyphal Form Cells in the Human Pathogen Candida Glabrata [C] . Luis Frazao, Rui Santos, Miguel Cacho Teixeira, International conference on advanced intelligent computing theories and applications . 2015

机译：自动检测人类病原假丝酵母念珠菌中的酵母菌和假菌丝形式的细胞

5. Diversity of Cytokine Expression Patterns in the Th1-Dominated Human Anti-Influenza CD4 T Cell Response Is Due To Both Variable Expression of Cytokines by Committed Th1 Cells, and a Minor Population of Uncommitted IL-2+IFNγ- Thpp Cells [D] . Deng, Nan 2014

机译：Th1为主的人类抗流感CD4 T细胞反应中细胞因子表达模式的多样性是由于既定的Th1细胞可变表达细胞因子，以及少数未定型的IL-2 +IFNγ-Thpp细胞引起的。

6. Decreasing Cell Population of Individual Candida Species Does Not Impair the Virulence of Candida albicans and Candida glabrata Mixed Biofilms [O] . Qianqian Li, Juanjuan Liu, Jing Shao, -1

机译：减少单个念珠菌物种的细胞种群不会损害白色念珠菌和光滑念珠菌混合生物膜的毒力

7. Generational distribution of a Candida glabrata population: Resilient old cells prevail, while younger cells dominate in the vulnerable host. [O] . Tejas Bouklas, Luz Alonso-Crisóstomo, Tamás Székely, 2017

机译：光滑念珠菌群体的代际分布：具有弹性的老细胞占优势，而较年轻的细胞在脆弱的宿主中占主导地位。

1. 树突状细胞在宿主抗白色念珠菌感染中的激活信号通路 [J] . 赵赛男 ,胡雁 . 口腔医学研究 . 2011,第1期

2. 白念珠菌细胞壁结构及其与宿主相互作用的研究进展 [J] . 梅一堃 ,谭镜璁 ,王安君 . 上海交通大学学报（医学版） . 2021,第009期

3. 纤维粘连蛋白在介导白念珠菌与宿主细胞粘附中的作用 [J] . 刘晓红 ,廖万清 ,胡惠民 . 临床皮肤科杂志 . 1999,第6期

4. 白念珠菌与宿主细胞粘附机制的探讨 [J] . 刘晓红 ,廖万清 ,胡惠民 . 中国皮肤性病学杂志 . 1999,第2期

5. 热处理光滑念珠菌对大鼠气道上皮细胞Dectin-1、IL-6和 TNF-α表达的影响 [J] . 张雪 ,骆雪萍 ,白剑 . 重庆医学 . 2016,第007期

6. CRK1基因缺失对白念珠菌黏附、侵袭及宿主细胞因子表达的影响 [C] . 赵静 ,刘继勇 ,张海 . 全国首届真菌感染与宿主免疫学术研讨会 . 2014

7. 迟缓爱德华氏菌易感细胞模型的建立及病原菌-宿主细胞互作研究 [A] . 王斌 . 2013

1. 来自白念珠菌的甘油－3－磷酸脱氢酶,其编码基因,包含其的载体和宿主细胞,生产甘油的方法 [P] . 中国专利： CN100386432C . 2008.05.07

2. 密码子优化的cry1Da核酸分子、核酸构建体、载体、宿主细胞、植物细胞、转基因植物、转化细胞的方法、生产转基因植物的方法、控制作物植物中的无脊椎害虫的方法和该核酸分子的用途 [P] . 中国专利： CN113195723A . 2021-07-30

3. compound, stable antibody-producing cell line, composition, methods for modulating an immune response in an individual and for treating and / or preventing disease, uses of a compound and / or composition and dendritic cells or precursors thereof, methods to enrich and detect dendritic cells or a subset or precursors thereof, polypeptide, vector polynucleotide, host cell, transgenic plant, transgenic non-human animal, extract, process for preparing a compound or polypeptide, enriched dendritic cell population and / or precursors expanded dendritic cell population and / or precursors thereof, methods for identifying a molecule that binds to a polypeptide and screening for a compound that binds to a polypeptide, use of a polypeptide, a polynucleotide, a vector , a host cell, a transgenic plant, an extract, a cell population and / or a composition. tion, method for producing a compound, and kit. [P] . 外国专利： BRPI0815848A2 . 2017-06-06

机译：化合物，稳定的抗体产生细胞系，组合物，调节个体免疫应答和治疗和/或预防疾病的方法，化合物和/或组合物和树突状细胞或其前体的用途，富集和检测树突状细胞的方法细胞或其子集或前体，多肽，载体多核苷酸，宿主细胞，转基因植物，转基因非人类动物，提取物，化合物或多肽的制备方法，富集的树突状细胞群和/或前体扩增的树突状细胞群和/或其前体，鉴定与多肽结合的分子并筛选与多肽结合的化合物的方法，多肽，多核苷酸，载体，宿主细胞，转基因植物，提取物，细胞群的用途和/或构图。，化合物的生产方法和试剂盒。

4. isolated nucleic acid molecule, host cell, non-human transgenic animal, isolated protein, antisense oligonucleotide, sirna molecule, isolated antibody, screening methods for test compounds capable of inhibiting, enhancing or mimicking gitrl interaction with gitr, to diagnose disease, to treat a patient at risk or diagnosed with a disease, to induce and to inhibit the proliferation of a cell population containing effector cells, to block the suppression and suppression of a cell population that includes t cells. effectors in the presence of cd4 + cd25 + regulatory t cells, and to treat a disease, pharmaceutical composition, and vaccine adjuvant [P] . 外国专利： BRPI0410785A . 2006-06-20

机译：分离的核酸分子，宿主细胞，非人类转基因动物，分离的蛋白，反义寡核苷酸，sirna分子，分离的抗体，能够抑制，增强或模拟gitrl与gitr相互作用，诊断疾病，治疗疾病的测试化合物的筛选方法处于风险中或被诊断患有疾病的患者，以诱导和抑制含有效应细胞的细胞群的增殖，以阻止对包括t细胞的细胞群的抑制和抑制。 cd4 + cd25 +调节性t细胞存在下的效应子，并用于治疗疾病，药物组合物和疫苗佐剂

5. Nucleic acid, vector, host cell, methods for the preparation of a bacterial strain variant classification, marking, the generation and control of bacterial populations, lineage and the bacterial cell variant, kit, use of a nucleic acid, cell cultivation, product, process The preparation of products, mutants of phage and phage mutant exhaust [P] . 外国专利： BR112013009583A2 . 2017-05-30

机译：核酸，载体，宿主细胞，细菌菌株变异体的制备方法，标记，细菌种群的产生和控制，谱系和细菌细胞变异体，试剂盒，核酸的用途，细胞培养，产品，方法制备产品，噬菌体突变体和噬菌体突变体尾气

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Generational distribution of a Candida glabrata population: Resilient old cells prevail while younger cells dominate in the vulnerable host

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