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Post-acute sequelae of SARS-CoV-2 cardiovascular symptoms are associated with trace-level cytokines that affect cardiomyocyte function SARS-CoV-2 急性后遗症的心血管症状与影响心肌细胞功能的痕量细胞因子有关
IF 28.3 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-30 DOI: 10.1038/s41564-024-01838-z
Jane E. Sinclair, Courtney Vedelago, Feargal J. Ryan, Meagan Carney, Meredith A. Redd, Miriam A. Lynn, Branka Grubor-Bauk, Yuanzhao Cao, Anjali K. Henders, Keng Yih Chew, Deborah Gilroy, Kim Greaves, Larisa Labzin, Laura Ziser, Katharina Ronacher, Leanne M. Wallace, Yiwen Zhang, Kyle Macauslane, Daniel J. Ellis, Sudha Rao, Lucy Burr, Amanda Bain, Anjana Karawita, Benjamin L. Schulz, Junrong Li, David J. Lynn, Nathan Palpant, Alain Wuethrich, Matt Trau, Kirsty R. Short

An estimated 65 million people globally suffer from post-acute sequelae of COVID-19 (PASC), with many experiencing cardiovascular symptoms (PASC-CVS) like chest pain and heart palpitations. This study examines the role of chronic inflammation in PASC-CVS, particularly in individuals with symptoms persisting over a year after infection. Blood samples from three groups—recovered individuals, those with prolonged PASC-CVS and SARS-CoV-2-negative individuals—revealed that those with PASC-CVS had a blood signature linked to inflammation. Trace-level pro-inflammatory cytokines were detected in the plasma from donors with PASC-CVS 18 months post infection using nanotechnology. Importantly, these trace-level cytokines affected the function of primary human cardiomyocytes. Plasma proteomics also demonstrated higher levels of complement and coagulation proteins in the plasma from patients with PASC-CVS. This study highlights chronic inflammation’s role in the symptoms of PASC-CVS.

据估计,全球有 6500 万人患有 COVID-19 急性后遗症(PASC),其中许多人都有胸痛和心悸等心血管症状(PASC-CVS)。本研究探讨了慢性炎症在 PASC-CVS 中的作用,尤其是在感染后症状持续一年以上的人群中。从三组人(康复者、PASC-CVS 患者和 SARS-CoV-2 阴性患者)的血液样本中发现,PASC-CVS 患者的血液特征与炎症有关。利用纳米技术在感染后 18 个月的 PASC-CVS 献血者血浆中检测到了痕量水平的促炎细胞因子。重要的是,这些痕量级细胞因子会影响原代人类心肌细胞的功能。血浆蛋白质组学还显示,PASC-CVS 患者血浆中的补体和凝血蛋白水平较高。这项研究强调了慢性炎症在 PASC-CVS 症状中的作用。
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引用次数: 0
A cross-systems primer for synthetic microbial communities 合成微生物群落的跨系统入门指南
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-30 DOI: 10.1038/s41564-024-01827-2
Elijah C. Mehlferber, Gontran Arnault, Bishnu Joshi, Laila P. Partida-Martinez, Kathryn A. Patras, Marie Simonin, Britt Koskella
The design and use of synthetic communities, or SynComs, is one of the most promising strategies for disentangling the complex interactions within microbial communities, and between these communities and their hosts. Compared to natural communities, these simplified consortia provide the opportunity to study ecological interactions at tractable scales, as well as facilitating reproducibility and fostering interdisciplinary science. However, the effective implementation of the SynCom approach requires several important considerations regarding the development and application of these model systems. There are also emerging ethical considerations when both designing and deploying SynComs in clinical, agricultural or environmental settings. Here we outline current best practices in developing, implementing and evaluating SynComs across different systems, including a focus on important ethical considerations for SynCom research. Here the authors outline best practices for the development, implementation and evaluation of synthetic microbial communities (or SynComs) across different systems.
合成群落(SynComs)的设计和使用是最有前途的策略之一,可用于揭示微生物群落内部以及这些群落与其宿主之间复杂的相互作用。与自然群落相比,这些简化的联合体为在可控尺度上研究生态相互作用提供了机会,同时也有利于可重复性和促进跨学科科学的发展。然而,要有效实施 SynCom 方法,需要在开发和应用这些模型系统时考虑几个重要因素。在临床、农业或环境环境中设计和部署综合观测系统时,还需要考虑新出现的伦理问题。在此,我们将概述目前在不同系统中开发、实施和评估 SynComs 的最佳实践,包括重点关注 SynCom 研究的重要伦理考虑因素。
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引用次数: 0
Community standards and future opportunities for synthetic communities in plant–microbiota research 植物微生物群落研究中的群落标准和合成群落的未来机遇
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-30 DOI: 10.1038/s41564-024-01833-4
Trent R. Northen, Manuel Kleiner, Marta Torres, Ákos T. Kovács, Mette Haubjerg Nicolaisen, Dorota M. Krzyżanowska, Shilpi Sharma, George Lund, Lars Jelsbak, Oliver Baars, Nikolaj Lunding Kindtler, Kathrin Wippel, Caja Dinesen, Jessica A. Ferrarezi, Malek Marian, Adele Pioppi, Xinming Xu, Tonni Andersen, Niko Geldner, Paul Schulze-Lefert, Julia A. Vorholt, Ruben Garrido-Oter
Harnessing beneficial microorganisms is seen as a promising approach to enhance sustainable agriculture production. Synthetic communities (SynComs) are increasingly being used to study relevant microbial activities and interactions with the plant host. Yet, the lack of community standards limits the efficiency and progress in this important area of research. To address this gap, we recommend three actions: (1) defining reference SynComs; (2) establishing community standards, protocols and benchmark data for constructing and using SynComs; and (3) creating an infrastructure for sharing strains and data. We also outline opportunities to develop SynCom research through technical advances, linking to field studies, and filling taxonomic blind spots to move towards fully representative SynComs. Here the authors discuss the use of synthetic communities, or SynComs, in plant–microbiome research and propose steps to develop community standards that will support future research.
利用有益微生物被视为提高可持续农业生产的一种有前途的方法。合成群落(SynComs)正被越来越多地用于研究相关的微生物活动以及与植物宿主的相互作用。然而,群落标准的缺乏限制了这一重要研究领域的效率和进展。为弥补这一不足,我们建议采取三项行动:(1) 界定参考 SynComs;(2) 建立构建和使用 SynComs 的社区标准、协议和基准数据;(3) 创建共享菌株和数据的基础设施。我们还概述了通过技术进步、与实地研究的联系以及填补分类学盲点来发展 SynCom 研究的机会,以迈向具有充分代表性的 SynCom。
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引用次数: 0
Design and reporting of prebiotic and probiotic clinical trials in the context of diet and the gut microbiome 从饮食和肠道微生物组的角度设计和报告益生菌和益生菌临床试验
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-30 DOI: 10.1038/s41564-024-01831-6
Kevin Whelan, Margaret Alexander, Claire Gaiani, Genelle Lunken, Andrew Holmes, Heidi M. Staudacher, Stephan Theis, Maria L. Marco
Diet is a major determinant of the gastrointestinal microbiome composition and function, yet our understanding of how it impacts the efficacy of prebiotics and probiotics is limited. Here we examine current evidence of dietary influence on prebiotic and probiotic efficacy in human studies, including potential mechanisms. We propose that habitual diet be included as a variable in prebiotic and probiotic intervention studies. This recommendation is based on the potential mechanisms via which diet can affect study outcomes, either directly or through the gut microbiome. We consider the challenges and opportunities of dietary assessment in this context. Lastly, we provide recommendations for the design, conduct and reporting of human clinical trials of prebiotics and probiotics (and other biotic interventions) to account for any effect of diet and nutrition. Here the authors make recommendations for the design of clinical trials for prebiotics and probiotics that includes consideration of diet and the gut microbiome.
饮食是胃肠道微生物组组成和功能的主要决定因素,但我们对饮食如何影响益生菌和益生菌功效的了解却很有限。在此,我们研究了目前人类研究中饮食对益生元和益生菌功效影响的证据,包括潜在的机制。我们建议将习惯性饮食作为变量纳入益生菌和益生元干预研究中。这一建议是基于饮食可直接或通过肠道微生物组影响研究结果的潜在机制。在此背景下,我们考虑了膳食评估的挑战和机遇。最后,我们为益生元和益生菌(以及其他生物干预)人体临床试验的设计、实施和报告提供了建议,以考虑膳食和营养的任何影响。
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引用次数: 0
Collateral sensitivity counteracts the evolution of antifungal drug resistance in Candida auris 附带敏感性抵消了白色念珠菌抗真菌药物耐药性的演变
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-29 DOI: 10.1038/s41564-024-01811-w
Hans Carolus, Dimitrios Sofras, Giorgio Boccarella, Stef Jacobs, Vladislav Biriukov, Louise Goossens, Alicia Chen, Ina Vantyghem, Tibo Verbeeck, Siebe Pierson, Celia Lobo Romero, Hans Steenackers, Katrien Lagrou, Pieter van den Berg, Judith Berman, Toni Gabaldón, Patrick Van Dijck
Antifungal drug resistance represents a serious global health threat, necessitating new treatment strategies. Here we investigated collateral sensitivity (CS), in which resistance to one drug increases sensitivity to another, and cross-resistance (XR), in which one drug resistance mechanism reduces susceptibility to multiple drugs, since CS and XR dynamics can guide treatment design to impede resistance development, but have not been systematically explored in pathogenic fungi. We used experimental evolution and mathematical modelling of Candida auris population dynamics during cyclic and combined drug exposures and found that especially CS-based drug cycling can effectively prevent the emergence of drug resistance. In addition, we found that a CS-based treatment switch can actively select against or eradicate resistant sub-populations, highlighting the potential to consider CS in therapeutic decision-making upon resistance detection. Furthermore, we show that some CS trends are robust among different strains and resistance mechanisms. Overall, these findings provide a promising direction for improved antifungal treatment approaches. Collateral-sensitivity-based drug cycling effectively prevents and impedes the evolution of antifungal drug resistance in Candida auris.
抗真菌药物耐药性是对全球健康的严重威胁,因此必须采取新的治疗策略。在这里,我们研究了附带敏感性(CS)和交叉耐药性(XR),前者是指对一种药物的耐药性会增加对另一种药物的敏感性,后者是指一种耐药机制会降低对多种药物的敏感性。我们利用实验演化和数学建模研究了循环和联合用药期间的白色念珠菌种群动态,发现尤其是基于 CS 的药物循环可以有效防止耐药性的产生。此外,我们还发现,基于 CS 的治疗转换可以主动选择抗药性亚群或根除抗药性亚群,这突出了在检测到抗药性时在治疗决策中考虑 CS 的潜力。此外,我们还发现,某些 CS 趋势在不同菌株和耐药机制之间具有稳健性。总之,这些发现为改进抗真菌治疗方法提供了一个很有前景的方向。
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引用次数: 0
Persistent viral RNA and protein contribute to post-acute pathology 持续存在的病毒 RNA 和蛋白质导致了急性期后的病理变化
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-28 DOI: 10.1038/s41564-024-01837-0
Keng Yih Chew, Kirsty R. Short
Viral RNA and protein are found to persist in infected lungs and contribute to post-acute pathology in Sendai virus infection.
发现病毒 RNA 和蛋白质会在受感染的肺部持续存在,并导致仙台病毒感染后的急性病理变化。
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引用次数: 0
Guiding phage therapy with genomic surveillance 用基因组监测指导噬菌体疗法
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-28 DOI: 10.1038/s41564-024-01836-1
Lorenz Leitner, Shawna McCallin
Integrating global and local genomic surveillance into phage therapy cocktail design offers a middle ground between personalized and product-based treatment options.
将全球和地方基因组监测纳入噬菌体疗法鸡尾酒的设计,提供了一种介于个性化治疗方案和基于产品的治疗方案之间的中间方案。
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引用次数: 0
PcdA promotes orthogonal division plane selection in Staphylococcus aureus PcdA 促进金黄色葡萄球菌的正交分裂面选择
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-28 DOI: 10.1038/s41564-024-01821-8
Félix Ramos-León, Brandon R. Anjuwon-Foster, Vivek Anantharaman, Taylor B. Updegrove, Colby N. Ferreira, Amany M. Ibrahim, Chin-Hsien Tai, Michael J. Kruhlak, Dominique M. Missiakas, Jodi L. Camberg, L. Aravind, Kumaran S. Ramamurthi
The bacterial pathogen, Staphylococcus aureus, grows by dividing in two alternating orthogonal planes. How these cell division planes are positioned correctly is not known. Here we used chemical genetic screening to identify PcdA as a division plane placement factor. Molecular biology and imaging approaches revealed non-orthogonal division plane selection for pcdA mutant bacteria. PcdA is a structurally and functionally altered member of the McrB AAA+ NTPase family, which are often found as restriction enzyme subunits. PcdA interacts with the tubulin-like divisome component, FtsZ, and the structural protein, DivIVA; it also localizes to future cell division sites. PcdA multimerization, localization and function are NTPase activity-dependent. We propose that the DivIVA/PcdA complex recruits unpolymerized FtsZ to assemble along the proper cell division plane. Although pcdA deletion did not affect S. aureus growth in several laboratory conditions, its clustered growth pattern was disrupted, sensitivity to cell-wall-targeting antibiotics increased and virulence in mice decreased. We propose that the characteristic clustered growth pattern of S. aureus, which emerges from dividing in alternating orthogonal division planes, might protect the bacterium from host defences. PcdA interacts with DivIVA and FtsZ, promoting Z-ring formation and division plane selection in Staphylococcus aureus, which increases virulence in mice and reduces sensitivity to cell-wall-targeting antibiotics.
细菌病原体金黄色葡萄球菌通过在两个交替的正交平面上分裂生长。这些细胞分裂平面如何正确定位尚不清楚。在这里,我们利用化学遗传筛选方法确定了 PcdA 作为分裂平面定位因子。分子生物学和成像方法揭示了 pcdA 突变细菌的非正交分裂平面选择。PcdA 是 McrB AAA+ NTPase 家族的一个结构和功能改变的成员,通常作为限制酶亚基存在。PcdA 与管蛋白样分裂体成分 FtsZ 和结构蛋白 DivIVA 相互作用;它还定位到未来的细胞分裂位点。PcdA 的多聚化、定位和功能都依赖于 NTPase 的活性。我们认为,DivIVA/PcdA 复合物能吸引未聚合的 FtsZ 沿正确的细胞分裂平面聚集。虽然 pcdA 缺失并不影响金黄色葡萄球菌在多种实验室条件下的生长,但它的集群生长模式被破坏,对细胞壁靶向抗生素的敏感性增加,对小鼠的毒力降低。我们认为,金黄色葡萄球菌在正交分裂平面上交替分裂所产生的特征性集群生长模式可能会保护该细菌免受宿主防御的影响。
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引用次数: 0
Pseudomonas aeruginosa faces a fitness trade-off between mucosal colonization and antibiotic tolerance during airway infection 在气道感染过程中,铜绿假单胞菌面临着粘膜定植和抗生素耐受性之间的适应性权衡
IF 28.3 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-25 DOI: 10.1038/s41564-024-01842-3
Lucas A. Meirelles, Evangelia Vayena, Auriane Debache, Eric Schmidt, Tamara Rossy, Tania Distler, Vassily Hatzimanikatis, Alexandre Persat

Pseudomonas aeruginosa frequently causes antibiotic-recalcitrant pneumonia, but the mechanisms driving its adaptation during human infections remain unclear. To reveal the selective pressures and adaptation strategies at the mucosal surface, here we investigated P. aeruginosa growth and antibiotic tolerance in tissue-engineered airways by transposon insertion sequencing (Tn-seq). Metabolic modelling based on Tn-seq data revealed the nutritional requirements for P. aeruginosa growth, highlighting reliance on glucose and lactate and varying requirements for amino acid biosynthesis. Tn-seq also revealed selection against biofilm formation during mucosal growth in the absence of antibiotics. Live imaging in engineered organoids showed that biofilm-dwelling cells remained sessile while colonizing the mucosal surface, limiting nutrient foraging and reduced growth. Conversely, biofilm formation increased antibiotic tolerance at the mucosal surface. Moreover, mutants with exacerbated biofilm phenotypes protected less tolerant but more cytotoxic strains, contributing to phenotypic heterogeneity. P. aeruginosa must therefore navigate conflicting physical and biological selective pressures to establish chronic infections.

铜绿假单胞菌经常引起抗生素拮抗性肺炎,但其在人类感染过程中的适应机制尚不清楚。为了揭示铜绿假单胞菌在粘膜表面的选择性压力和适应策略,我们通过转座子插入测序(Tn-seq)研究了铜绿假单胞菌在组织工程气道中的生长和抗生素耐受性。基于 Tn-seq 数据的代谢模型揭示了铜绿假单胞菌生长的营养需求,突出了对葡萄糖和乳酸的依赖以及对氨基酸生物合成的不同需求。Tn-seq 还揭示了在没有抗生素的情况下粘膜生长过程中对生物膜形成的选择。工程有机体的实时成像显示,生物膜栖息细胞在粘膜表面定殖时保持无柄状态,从而限制了营养物质的觅食并降低了生长速度。相反,生物膜的形成增加了粘膜表面对抗生素的耐受性。此外,生物膜表型加剧的突变体保护了耐受性较差但细胞毒性更强的菌株,从而促进了表型的异质性。因此,铜绿假单胞菌必须在相互冲突的物理和生物选择压力下建立慢性感染。
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引用次数: 0
Metagenomic characterization of viruses and mobile genetic elements associated with the DPANN archaeal superphylum 与 DPANN 古菌超门相关的病毒和移动遗传元素的元基因组特征
IF 28.3 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-10-24 DOI: 10.1038/s41564-024-01839-y
Zongzhi Wu, Shufeng Liu, Jinren Ni

The archaeal superphylum DPANN (an acronym formed from the initials of the first five phyla discovered: Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanohaloarchaeota and Nanoarchaeota) is a group of ultrasmall symbionts able to survive in extreme ecosystems. The diversity and dynamics between DPANN archaea and their virome remain largely unknown. Here we use a metagenomic clustered regularly interspaced short palindromic repeats (CRISPR) screening approach to identify 97 globally distributed, non-redundant viruses and unclassified mobile genetic elements predicted to infect hosts across 8 DPANN phyla, including 7 viral groups not previously characterized. Genomic analysis suggests a diversity of viral morphologies including head-tailed, tailless icosahedral and spindle-shaped viruses with the potential to establish lytic, chronic or lysogenic infections. We also find evidence of a virally encoded Cas12f1 protein (probably originating from uncultured DPANN archaea) and a mini-CRISPR array, which could play a role in modulating host metabolism. Many metagenomes have virus-to-host ratios >10, indicating that DPANN viruses play an important role in controlling host populations. Overall, our study illuminates the underexplored diversity, functional repertoires and host interactions of the DPANN virome.

古菌超门 DPANN(由最先发现的五个门的首字母缩写组成:DPANN是一个超小型共生菌群,能够在极端生态系统中生存。DPANN 古菌及其病毒体之间的多样性和动态关系在很大程度上仍不为人所知。在这里,我们使用一种元基因组聚类规律性间隔短回文重复序列(CRISPR)筛选方法,鉴定出 97 种全球分布的非冗余病毒和未分类的移动遗传因子,预测它们会感染 8 个 DPANN 门的宿主,其中包括 7 个以前没有表征过的病毒群。基因组分析表明了病毒形态的多样性,包括有头尾病毒、无尾二十面体病毒和纺锤形病毒,它们都有可能造成溶解性、慢性或溶源性感染。我们还发现了病毒编码的 Cas12f1 蛋白(可能源自未培养的 DPANN 古菌)和微型CRISPR 阵列的证据,它们可能在调节宿主新陈代谢方面发挥作用。许多元基因组的病毒与宿主比率为10,这表明DPANN病毒在控制宿主种群方面发挥着重要作用。总之,我们的研究揭示了 DPANN 病毒组未被充分探索的多样性、功能谱系和宿主相互作用。
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引用次数: 0
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Nature Microbiology
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