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A trivalent mucosal vaccine encoding phylogenetically inferred ancestral RBD sequences confers pan-Sarbecovirus protection in mice 编码系统发育推断出的祖先 RBD 序列的三价粘膜疫苗可为小鼠提供泛沙巴病毒保护
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-11-18 DOI: 10.1016/j.chom.2024.10.016
James Brett Case, Shilpa Sanapala, Carly Dillen, Victoria Rhodes, Christian Zmasek, Taras M. Chicz, Charlotte E. Switzer, Suzanne M. Scheaffer, George Georgiev, Catherine Jacob-Dolan, Blake M. Hauser, Déborah Carolina Carvalho Dos Anjos, Lucas J. Adams, Nadia Soudani, Chieh-Yu Liang, Baoling Ying, Ryan P. McNamara, Richard H. Scheuermann, Adrianus C.M. Boon, Daved H. Fremont, Michael S. Diamond
The continued emergence of SARS-CoV-2 variants and the threat of future Sarbecovirus zoonoses have spurred the design of vaccines that can induce broad immunity against multiple coronaviruses. Here, we use computational methods to infer ancestral phylogenetic reconstructions of receptor binding domain (RBD) sequences across multiple Sarbecovirus clades and incorporate them into a multivalent adenoviral-vectored vaccine. Mice immunized with this pan-Sarbecovirus vaccine are protected in the upper and lower respiratory tracts against infection by historical and contemporary SARS-CoV-2 variants, SARS-CoV, and pre-emergent SHC014 and Pangolin/GD coronavirus strains. Using genetic and immunological approaches, we demonstrate that vaccine-induced protection unexpectedly is conferred principally by CD4+ and CD8+ T cell-mediated anamnestic responses. Importantly, prior mRNA vaccination or SARS-CoV-2 respiratory infection does not alter the efficacy of the mucosally delivered pan-Sarbecovirus vaccine. These data highlight the promise of a phylogenetic approach for antigen and vaccine design against existing and pre-emergent Sarbecoviruses with pandemic potential.
SARS-CoV-2 变异体的不断出现以及未来 Sarbecovirus 人畜共患病的威胁促使人们设计能诱导多种冠状病毒广泛免疫的疫苗。在本文中,我们使用计算方法推断了多个沙棘病毒支系的受体结合域(RBD)序列的祖先系统发育重建,并将其纳入多价腺病毒载体疫苗中。小鼠接种这种泛沙士病毒疫苗后,上呼吸道和下呼吸道均可免受历史和当代 SARS-CoV-2 变体、SARS-CoV 以及 SHC014 和 Pangolin/GD 冠状病毒毒株的感染。我们利用遗传学和免疫学方法证明,疫苗诱导的保护作用出乎意料地主要由 CD4+ 和 CD8+ T 细胞介导的过敏反应产生。重要的是,之前的 mRNA 疫苗接种或 SARS-CoV-2 呼吸道感染不会改变粘膜递送的泛沙士病毒疫苗的功效。这些数据凸显了系统发育方法在抗原和疫苗设计方面的前景,这种方法可用于抗击现有的和爆发前的具有大流行潜力的沙士病毒。
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引用次数: 0
Harnessing biosynthesized selenium nanoparticles for recruitment of beneficial soil microbes to plant roots 利用生物合成的硒纳米颗粒招募有益的土壤微生物进入植物根系
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-11-18 DOI: 10.1016/j.chom.2024.10.015
Chenyu Sun, Bin Sun, Lin Chen, Meilin Zhang, Pingping Lu, Mengfan Wu, Quanhong Xue, Qiao Guo, Dejian Tang, Hangxian Lai
Root exudates can benefit plant growth and health by reshaping the rhizosphere microbiome. Whether nanoparticles biosynthesized by rhizosphere microbes play a similar role in plant microbiome manipulation remains enigmatic. Herein, we collect elemental selenium nanoparticles (SeNPs) from selenobacteria associated with maize roots. In vitro and soil assays show that the SeNPs enhanced plant performance by recruiting plant growth-promoting bacteria (e.g., Bacillus) in a dose-dependent manner. Multiomic profilings unravel a cross-kingdom-signaling cascade that mediates efficient biosynthesis of SeNPs by selenobacteria. Specifically, maize roots perceive histamine signaling from Bacillus spp., which stimulates the plant to produce p-coumarate via root exudation. The rpoS gene in selenobacteria (e.g., Pseudomonas sp. ZY71) responds to p-coumarate signaling and positively regulates the biosynthesis of SeNPs. This study demonstrates a novel mechanism for recruiting host-beneficial soil microbes by microbially synthesized nanoparticles and unlocks promising possibilities for plant microbiome manipulation.
根渗出物可以通过重塑根圈微生物组来促进植物生长和健康。根圈微生物生物合成的纳米颗粒是否在植物微生物群操纵中发挥类似作用仍是一个谜。在这里,我们从与玉米根系相关的硒细菌中收集元素硒纳米颗粒(SeNPs)。体外和土壤试验表明,SeNPs 能以剂量依赖的方式招募促进植物生长的细菌(如芽孢杆菌),从而提高植物的生长性能。多组学分析揭示了硒细菌高效生物合成 SeNPs 的跨领域信号级联。具体来说,玉米根部能感知来自芽孢杆菌的组胺信号,从而刺激植物通过根部渗出产生对香豆酸盐。硒细菌(如假单胞菌 ZY71)中的 rpoS 基因会响应对香豆酸信号,并积极调节 SeNPs 的生物合成。这项研究展示了微生物合成的纳米颗粒招募对宿主有益的土壤微生物的新机制,并为植物微生物组的操纵提供了广阔的前景。
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引用次数: 0
A bacterial sialidase mediates early-life colonization by a pioneering gut commensal 一种细菌硅糖苷酶介导先驱肠道共生菌的早期定殖
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-01-15 DOI: 10.1016/j.chom.2023.12.014
Ekaterina Buzun, Chia-Yun Hsu, Kristija Sejane, Renee E. Oles, Adriana Vasquez Ayala, Luke R. Loomis, Jiaqi Zhao, Leigh-Ana Rossitto, Dominic M. McGrosso, David J. Gonzalez, Lars Bode, Hiutung Chu

The early microbial colonization of the gastrointestinal tract can have long-term impacts on development and health. Keystone species, including Bacteroides spp., are prominent in early life and play crucial roles in maintaining the structure of the intestinal ecosystem. However, the process by which a resilient community is curated during early life remains inadequately understood. Here, we show that a single sialidase, NanH, in Bacteroides fragilis mediates stable occupancy of the intestinal mucosa in early life and regulates a commensal colonization program. This program is triggered by sialylated glycans, including those found in human milk oligosaccharides and intestinal mucus. NanH is required for vertical transmission from dams to pups and promotes B. fragilis dominance during early life. Furthermore, NanH facilitates commensal resilience and recovery after antibiotic treatment in a defined microbial community. Collectively, our study reveals a co-evolutionary mechanism between the host and microbiota mediated through host-derived glycans to promote stable colonization.

胃肠道的早期微生物定植会对发育和健康产生长期影响。包括乳杆菌属在内的基石物种在生命早期非常突出,在维持肠道生态系统结构方面发挥着至关重要的作用。然而,人们对生命早期弹性群落的形成过程仍不甚了解。在这里,我们发现脆弱拟杆菌(Bacteroides fragilis)中的单个硅糖苷酶(NanH)能在生命早期稳定地占据肠粘膜,并调节共生定殖程序。这种程序是由包括母乳低聚糖和肠粘液中的糖在内的糖基化聚糖触发的。从母体到幼崽的垂直传播需要 NanH,它能促进脆弱拟杆菌在生命早期的优势地位。此外,在一个确定的微生物群落中,NanH 还能促进共生菌的恢复能力以及抗生素治疗后的恢复。总之,我们的研究揭示了宿主与微生物群之间通过宿主衍生的聚糖促进稳定定殖的共同进化机制。
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引用次数: 0
Linking microbial genes to plasma and stool metabolites uncovers host-microbial interactions underlying ulcerative colitis disease course 将微生物基因与血浆和粪便代谢物联系起来,揭示溃疡性结肠炎病程中宿主与微生物之间的相互作用
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-01-11 DOI: 10.1016/j.chom.2023.12.013
Melanie Schirmer, Martin Stražar, Julian Avila-Pacheco, Daniel F. Rojas-Tapias, Eric M. Brown, Emily Temple, Amy Deik, Kevin Bullock, Sarah Jeanfavre, Kerry Pierce, Shen Jin, Rachele Invernizzi, Marie-Madlen Pust, Zach Costliow, David R. Mack, Anne M. Griffiths, Thomas Walters, Brendan M. Boyle, Subra Kugathasan, Hera Vlamakis, Ramnik J. Xavier

Understanding the role of the microbiome in inflammatory diseases requires the identification of microbial effector molecules. We established an approach to link disease-associated microbes to microbial metabolites by integrating paired metagenomics, stool and plasma metabolomics, and culturomics. We identified host-microbial interactions correlated with disease activity, inflammation, and the clinical course of ulcerative colitis (UC) in the Predicting Response to Standardized Colitis Therapy (PROTECT) pediatric inception cohort. In severe disease, metabolite changes included increased dipeptides and tauro-conjugated bile acids (BAs) and decreased amino-acid-conjugated BAs in stool, whereas in plasma polyamines (N-acetylputrescine and N1-acetylspermidine) increased. Using patient samples and Veillonella parvula as a model, we uncovered nitrate- and lactate-dependent metabolic pathways, experimentally linking V. parvula expansion to immunomodulatory tryptophan metabolite production. Additionally, V. parvula metabolizes immunosuppressive thiopurine drugs through xdhA xanthine dehydrogenase, potentially impairing the therapeutic response. Our findings demonstrate that the microbiome contributes to disease-associated metabolite changes, underscoring the importance of these interactions in disease pathology and treatment.

要了解微生物组在炎症性疾病中的作用,就必须鉴定微生物效应分子。我们建立了一种方法,通过整合配对元基因组学、粪便和血浆代谢组学以及培养组学,将疾病相关微生物与微生物代谢物联系起来。我们在溃疡性结肠炎(UC)标准化疗法反应预测(PROTECT)儿科起始队列中确定了宿主与微生物相互作用与疾病活动、炎症和临床过程的相关性。在重症患者中,代谢物的变化包括粪便中二肽和牛磺酸结合胆汁酸(BA)的增加和氨基酸结合胆汁酸(BA)的减少,而血浆中多胺(N-乙酰putrescine和N1-乙酰spermidine)的增加。利用患者样本和副嗜血杆菌作为模型,我们发现了硝酸盐和乳酸盐依赖性代谢途径,通过实验将副嗜血杆菌的扩增与免疫调节色氨酸代谢产物的产生联系起来。此外,副酵母菌通过 xdhA 黄嘌呤脱氢酶代谢免疫抑制硫嘌呤药物,可能会损害治疗反应。我们的研究结果表明,微生物组有助于疾病相关代谢物的变化,强调了这些相互作用在疾病病理和治疗中的重要性。
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引用次数: 0
Better than being aPARt: S. aureus itches to get close to sensory neurons 比 "被 "更好金黄色葡萄球菌渴望接近感觉神经元
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-01-10 DOI: 10.1016/j.chom.2023.12.011
Zhe Chen, Sha Huang, Yanlin Su

In a recent issue of Cell, Deng et al. show that S. aureus serine protease V8 triggers itch, independent of inflammation, by activating sensory neurons through PAR1. This study presents mechanistic insights into pruritogenic bacteria and their interactions with sensory neurons while providing a possible approach for treating itch-related diseases.

在最近一期的《细胞》(Cell)杂志上,Deng 等人的研究表明,金黄色葡萄球菌丝氨酸蛋白酶 V8 通过 PAR1 激活感觉神经元,从而引发瘙痒,与炎症无关。这项研究揭示了致瘙痒细菌及其与感觉神经元相互作用的机理,同时为治疗瘙痒相关疾病提供了一种可能的方法。
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引用次数: 0
The gut microbiome as a guidepost for infection risk in liver transplantation 肠道微生物组是肝移植感染风险的指针
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-01-10 DOI: 10.1016/j.chom.2023.12.005
Angelica T. Vieira, Thomas F. Baumert

In this issue, Lehmann et al. addresses the high infection risk in liver transplantation by examining the gut microbiome in a patient cohort. By uncovering a predictive role of the microbiome for the clinical course, the study unravels the gut microbiome as a guidepost for infection risk in liver transplantation.

在本期杂志中,Lehmann 等人通过研究患者队列中的肠道微生物组,探讨了肝移植中的高感染风险。通过发现微生物组对临床病程的预测作用,该研究揭示了肠道微生物组作为肝移植感染风险指导的作用。
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引用次数: 0
Persistent Salmonella infections in humans are associated with mutations in the BarA/SirA regulatory pathway 人类持续感染沙门氏菌与 BarA/SirA 调控途径中的突变有关
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-01-10 DOI: 10.1016/j.chom.2023.12.001
Alexandra Grote, Bar Piscon, Abigail L. Manson, Boaz Adani, Helit Cohen, Jonathan Livny, Ashlee M. Earl, Ohad Gal-Mor

Several bacterial pathogens, including Salmonella enterica, can cause persistent infections in humans by mechanisms that are poorly understood. By comparing genomes of isolates longitudinally collected from 256 prolonged salmonellosis patients, we identified repeated mutations in global regulators, including the barA/sirA two-component regulatory system, across multiple patients and Salmonella serovars. Comparative RNA-seq analysis revealed that distinct mutations in barA/sirA led to diminished expression of Salmonella pathogenicity islands 1 and 4 genes, which are required for Salmonella invasion and enteritis. Moreover, barA/sirA mutants were attenuated in an acute salmonellosis mouse model and induced weaker transcription of host immune responses. In contrast, in a persistent infection mouse model, these mutants exhibited long-term colonization and prolonged shedding. Taken together, these findings suggest that selection of mutations in global virulence regulators facilitates persistent Salmonella infection in humans, by attenuating Salmonella virulence and inducing a weaker host inflammatory response.

包括肠炎沙门氏菌在内的几种细菌病原体可通过不甚明了的机制导致人类持续感染。通过比较从 256 名长期沙门氏菌病患者身上纵向收集的分离物基因组,我们发现了多个患者和沙门氏菌血清型的全局调控因子(包括 barA/sirA 双组分调控系统)发生了重复突变。RNA-seq比较分析表明,barA/sirA的不同突变导致沙门氏菌致病性岛1和4基因的表达减少,而这两个基因是沙门氏菌入侵和肠炎所必需的。此外,barA/sirA 突变体在急性沙门氏菌病小鼠模型中的作用减弱,诱导的宿主免疫反应转录也减弱。相反,在持续感染小鼠模型中,这些突变体表现出长期定植和长时间脱落。综上所述,这些研究结果表明,全局毒力调节因子突变的选择通过减弱沙门氏菌的毒力和诱导较弱的宿主炎症反应,有利于人类持续感染沙门氏菌。
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引用次数: 0
Another iron in C. difficile’s fire 艰难梭菌火中的另一块烙铁
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-01-10 DOI: 10.1016/j.chom.2023.12.008
Hal Drakesmith, Michael B. Zimmermann

Iron is arguably the most important nutrient in the ongoing battle between hosts and bacteria. Recently in Nature, a unique iron storage organelle, the ferrosome, was discovered in the human pathogen Clostridioides difficile.1 But what is the role of ferrosomes and how do they affect bacterial behavior and infection?

铁可以说是宿主与细菌之间持续斗争中最重要的营养物质。最近,《自然》杂志在人类病原体艰难梭菌中发现了一种独特的铁储存细胞器--铁粒体。
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引用次数: 0
“Messenger RNA just entered the chat”: The next layer of cross-kingdom RNA transfer "信使 RNA 刚刚进入聊天室":跨领域 RNA 转移的下一个层次
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-01-10 DOI: 10.1016/j.chom.2023.12.002
Alessa Ruf, Silke Robatzek

Infectious fungi send small RNAs into plant cells to enhance their virulence by silencing defense-related genes. In this issue of Cell Host & Microbe, Wang and colleagues show that full-length messenger RNA is transported in vesicles from plants to fungi, becoming translated by fungal ribosomes and reducing fungal pathogenicity.

传染性真菌向植物细胞发送小RNA,通过沉默防御相关基因来增强其毒力。在本期《细胞-宿主-微生物》(Cell Host & Microbe)杂志上,Wang 及其同事发现,全长信使 RNA 通过囊泡从植物运输到真菌,由真菌核糖体翻译,从而降低了真菌的致病性。
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引用次数: 0
Memory T cells effectively recognize the SARS-CoV-2 hypermutated BA.2.86 variant 记忆性 T 细胞能有效识别 SARS-CoV-2 BA.2.86 高突变变体
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-01-10 DOI: 10.1016/j.chom.2023.12.010
Thomas R. Müller, Yu Gao, Jinghua Wu, Oriana Ribeiro, Puran Chen, Peter Bergman, Ola Blennow, Lotta Hansson, Stephan Mielke, Piotr Nowak, Jan Vesterbacka, Mira Akber, Gunnar Söderdahl, C.I. Edvard Smith, Karin Loré, Margaret Sällberg Chen, Per Ljungman, Hanna M. Ingelman-Sundberg, Hans-Gustaf Ljunggren, Anders Österborg, Marcus Buggert

T cells are critical in mediating the early control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection. However, it remains unknown whether memory T cells can effectively cross-recognize new SARS-CoV-2 variants with a broad array of mutations, such as the emergent hypermutated BA.2.86 variant. Here, we report in two separate cohorts, including healthy controls and individuals with chronic lymphocytic leukemia, that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection or vaccination demonstrate resilient immune recognition of BA.2.86. In both cohorts, we found largely preserved SARS-CoV-2 spike-specific CD4+ and CD8+ T cell magnitudes against mutated spike epitopes of BA.2.86. Functional analysis confirmed that both cytokine expression and proliferative capacity of SARS-CoV-2 spike-specific T cells to BA.2.86-mutated spike epitopes are similarly sustained. In summary, our findings indicate that memory CD4+ and CD8+ T cells continue to provide cell-mediated immune recognition to highly mutated emerging variants such as BA.2.86.

在早期控制严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)突破性感染的过程中,T 细胞起着至关重要的作用。然而,记忆 T 细胞能否有效地交叉识别具有多种变异的 SARS-CoV-2 新变异,如新出现的高突变 BA.2.86 变异,目前仍是未知数。在这里,我们在两个不同的队列(包括健康对照组和慢性淋巴细胞白血病患者)中报告了由先前感染或接种疫苗诱导的 SARS-CoV-2 尖峰特异性 CD4+ 和 CD8+ T 细胞对 BA.2.86 的免疫识别能力。在两个队列中,我们发现针对 BA.2.86 变异尖峰表位的 SARS-CoV-2 尖峰特异性 CD4+ 和 CD8+ T 细胞数量基本保持不变。功能分析证实,SARS-CoV-2尖峰特异性T细胞对BA.2.86突变尖峰表位的细胞因子表达和增殖能力都得到了类似的维持。总之,我们的研究结果表明,记忆性 CD4+ 和 CD8+ T 细胞能继续对 BA.2.86 等高度突变的新变种提供细胞介导的免疫识别。
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引用次数: 0
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