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Coenzyme A metabolism: a key driver of gut microbiota dynamics and metabolic profiles. 辅酶A代谢:肠道微生物群动力学和代谢概况的关键驱动因素。
IF 12.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2025-01-14 DOI: 10.1093/femsre/fuaf051
Johanna Böttcher, Ody C M Sibon, Sahar El Aidy

Coenzyme A (CoA) biosynthesis is a crucial process in living organisms, characterized by the production of conserved intermediates through enzyme-catalysed steps that vary across species. The synthesis of CoA entails several conversions, starting from pantothenate. Pantothenate is an essential vitamin in humans and is synthesized by certain bacterial species. Intermediates of the biosynthetic pathway have been shown to impact bacteria, especially in community settings such as the intestinal microbiota. Additionally, various diseases have been associated with specific CoA precursors and metabolic pathways downstream of CoA in the gut microbiota, underscoring the significance of evaluating the current knowledge on how the CoA pathway influences the metabolic state of bacteria. This also highlights the importance of having standardized methodologies that can be employed to better understand the metabolism of the microbiome. In this review, we explore the current literature on bacterial CoA metabolism, with a particular focus on gut bacteria and the impact of CoA-related metabolites on bacterial composition, function and metabolism. Furthermore, we discuss previous and current methodologies employed to investigate CoA biosynthesis. Our goal is to provide valuable insights into the intricate relationship between CoA metabolism, gut microbiota and their implications for health and disease, offering a foundation for future research and therapeutic approaches.

辅酶A (CoA)的生物合成是生物体中一个至关重要的过程,其特点是通过酶催化的步骤产生保守的中间体,不同物种之间存在差异。辅酶a的合成需要从泛酸开始进行多次转化。泛酸盐是人体必需的维生素,由某些细菌合成。生物合成途径的中间产物已被证明会影响细菌,特别是在肠道微生物群等社区环境中。此外,各种疾病都与肠道微生物群中CoA及其下游代谢途径受损有关,这强调了评估CoA途径如何影响细菌代谢状态的现有知识的重要性。这也突出了标准化方法的重要性,可以用来更好地了解它们的新陈代谢。在这篇综述中,我们探讨了目前关于细菌CoA代谢的文献,特别关注肠道细菌以及CoA相关代谢物对细菌组成、功能和代谢的影响。此外,我们讨论了以前和目前用于研究辅酶a生物合成的方法。我们的目标是为CoA代谢,肠道微生物群及其对健康和疾病的影响之间的复杂关系提供有价值的见解,为未来的研究和治疗方法提供基础。
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引用次数: 0
Standardizing experimental approaches to investigate interactions between bacteria and ectomycorrhizal fungi. 规范研究细菌与外生菌根真菌相互作用的实验方法。
IF 12.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2025-01-14 DOI: 10.1093/femsre/fuae035
Louis Berrios, T Bertie Ansell, Peter D Dahlberg, Kabir G Peay

Bacteria and ectomycorrhizal fungi (EcMF) represent two of the most dominant plant root-associated microbial groups on Earth, and their interactions continue to gain recognition as significant factors that shape forest health and resilience. Yet, we currently lack a focused review that explains the state of bacteria-EcMF interaction research in the context of experimental approaches and technological advancements. To these ends, we illustrate the utility of studying bacteria-EcMF interactions, detail outstanding questions, outline research priorities in the field, and provide a suite of approaches that can be used to promote experimental reproducibility, field advancement, and collaboration. Though this review centers on the ecology of bacteria, EcMF, and trees, it by default offers experimental and conceptual insights that can be adapted to various subfields of microbiology and microbial ecology.

细菌和外生菌根真菌(EcMF)是地球上两种最主要的植物根系相关微生物群,它们之间的相互作用继续被认为是影响森林健康和恢复力的重要因素。然而,在实验方法和技术进步的背景下,我们目前缺乏一篇重点综述来解释细菌- ecmf相互作用研究的状态。为了达到这些目的,我们阐述了研究细菌- ecmf相互作用的效用,详细说明了悬而未决的问题,概述了该领域的研究重点,并提供了一套可用于促进实验可重复性,领域进步和合作的方法。虽然这篇综述集中在细菌、EcMF和树木的生态学上,但它默认提供了实验和概念上的见解,可以适应微生物学和微生物生态学的各个子领域。
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引用次数: 0
Hierarchical metabolic engineering for rewiring cellular metabolism. 重组细胞代谢的分层代谢工程。
IF 12.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2025-01-14 DOI: 10.1093/femsre/fuaf047
Tiantian Chai, Yuxuan Tao, Chunlei Zhao, Xiulai Chen

Metabolic engineering is a key enabling technology for rewiring cellular metabolism to enhance production of chemicals, biofuels, and materials from renewable resources. However, how to make cells into efficient factories is still challenging due to its robust metabolic networks. To open this door, metabolic engineering has realized great breakthroughs through three waves of technological research and innovations, especially the third wave. To understand the third wave of metabolic engineering better, we discuss its mainstream strategies and examples of its application at five hierarchies, including part, pathway, network, genome, and cell level, and provide insights as to how to rewire cellular metabolism in the context of maximizing product titer, yield, and productivity. Finally, we highlight future perspectives on metabolic engineering for the successful development of cell factories.

代谢工程是一项关键的使能技术,用于重新连接细胞代谢,以提高化学物质、生物燃料和可再生资源材料的生产。然而,由于其强大的代谢网络,如何使细胞成为高效的工厂仍然具有挑战性。为了打开这扇门,代谢工程通过三波技术研究和创新,特别是第三波,实现了巨大的突破。为了更好地理解第三波代谢工程,我们讨论了其主流策略及其在五个层次上的应用实例,包括部分,途径,网络,基因组和细胞水平,并提供了如何在最大化产品滴度,产量和生产力的背景下重新连接细胞代谢的见解。最后,我们强调了代谢工程对细胞工厂成功发展的未来展望。
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引用次数: 0
Exploring antiviral strategies to combat African swine fever. 探索对抗非洲猪瘟的抗病毒策略。
IF 12.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2025-01-14 DOI: 10.1093/femsre/fuaf044
Ana Catarina Urbano, Beatriz Melo, Fernando Ferreira

African swine fever (ASF), caused by the highly contagious African swine fever virus (ASFV), poses a significant threat to domestic and wild pigs worldwide. Despite its limited host range and lack of zoonotic potential, ASF has severe socio-economic and environmental consequences. Current control strategies primarily rely on early detection and culling of infected animals, but these measures are insufficient given the rapid spread of the disease. Developing effective therapeutics against ASFV is crucial to prevent further spread and mitigate economic losses. Although vaccination remains critical, recent vaccine approvals in Vietnam have raised safety and efficacy concerns. Moreover, as challenges persist in vaccine development and deployment, particularly in complex field conditions, antiviral agents have emerged as a critical complementary approach. These agents have the potential to mitigate side effects and control viral spread when vaccines alone are insufficient or when animals face simultaneous exposure to vaccine strains and wild-type viruses. However, advancing them from proof-of-concept to widespread practical application entails a significant interdisciplinary effort, given the logistical and economic constraints of in vivo testing. In this review, we examine emerging antiviral approaches and highlight key ASFV replication mechanisms and therapeutic targets to guide rational drug design amidst an evolving viral landscape.

非洲猪瘟(ASF)由高度传染性的非洲猪瘟病毒(ASFV)引起,对全世界的家猪和野猪构成重大威胁。尽管非洲猪瘟的宿主范围有限且缺乏人畜共患的潜力,但它具有严重的社会经济和环境后果。目前的控制战略主要依赖于早期发现和扑杀受感染的动物,但鉴于疾病的迅速传播,这些措施是不够的。开发针对非洲猪瘟的有效疗法对于防止进一步传播和减轻经济损失至关重要。尽管疫苗接种仍然至关重要,但越南最近批准的疫苗引起了人们对安全性和有效性的担忧。此外,由于疫苗开发和部署方面的挑战持续存在,特别是在复杂的实地条件下,抗病毒药物已成为一种关键的补充办法。当单独接种疫苗不足或动物同时暴露于疫苗毒株和野生型病毒时,这些制剂具有减轻副作用和控制病毒传播的潜力。然而,考虑到体内测试的后勤和经济限制,将它们从概念验证推进到广泛的实际应用需要大量的跨学科努力。在这篇综述中,我们研究了新兴的抗病毒方法,并强调了关键的ASFV复制机制和治疗靶点,以指导在不断变化的病毒环境中合理的药物设计。
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引用次数: 0
Charting the microbial frontier: a comprehensive guidebook for advancing microbiome research. 绘制微生物前沿:推进微生物组研究的综合指南。
IF 12.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2025-01-14 DOI: 10.1093/femsre/fuae033
Hui Wu
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引用次数: 0
Microbial engineering for monocyclic aromatic compounds production. 单环芳香族化合物生产的微生物工程。
IF 10.1 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2025-01-14 DOI: 10.1093/femsre/fuaf003
Guipeng Hu, Cong Gao, Xiaomin Li, Wei Song, Jing Wu

Aromatic compounds serve pivotal roles in plant physiology and exhibit antioxidative and antimicrobial properties, leading to their widespread application, such as in food preservation and pharmaceuticals. However, direct plant extraction and petrochemical synthesis often struggle to meet current needs due to low yield or facing economic and environmental hurdles. In the past decades, systems metabolic engineering enabled eco-friendly production of various aromatic compounds, with some reaching industrial levels. In this review, we highlight monocyclic aromatic chemicals, which have relatively simple structures and are currently the primary focus of microbial synthesis research. We then discuss systems metabolic engineering at the enzyme, pathway, cellular, and bioprocess levels to improve the production of these chemicals. Finally, we overview the current limitations and potential resolution strategies, aiming to provide reference for future studies on the biosynthesis of aromatic products.

芳香族化合物在植物生理中起着举足轻重的作用,并具有抗氧化和抗菌的特性,因此在食品保鲜和制药等领域得到了广泛的应用。然而,由于产量低或面临经济和环境障碍,直接植物提取和石化合成往往难以满足当前的需求。在过去的几十年里,系统代谢工程使各种芳香族化合物的环保生产成为可能,其中一些达到了工业水平。在本文中,我们重点介绍了结构相对简单的单环芳香族化学物质,这是目前微生物合成研究的主要焦点。然后,我们在酶、途径、细胞和生物过程水平上讨论系统代谢工程,以改善这些化学物质的生产。最后,综述了目前存在的局限性和潜在的解决策略,旨在为未来芳香族生物合成的研究提供参考。
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引用次数: 0
In silico encounters: harnessing metabolic modelling to understand plant-microbe interactions. 在计算机相遇:利用代谢模型来理解植物与微生物的相互作用。
IF 12.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2025-01-14 DOI: 10.1093/femsre/fuaf030
Martina Feierabend, Nadine Töpfer

Understanding plant-microbe interactions is vital for developing sustainable agricultural practices and mitigating the consequences of climate change on food security. Plant-microbe interactions can improve nutrient acquisition, reduce dependency on chemical fertilizers, affect plant health, growth, and yield, and impact plants' resistance to biotic and abiotic stresses. These interactions are largely driven by metabolic exchanges and can thus be understood through metabolic network modelling. Recent developments in genomics, metagenomics, phenotyping, and synthetic biology now enable researchers to harness the potential of metabolic modelling at the genome scale. Here, we review studies that utilize genome-scale metabolic modelling to study plant-microbe interactions in symbiotic, pathogenic, and microbial community systems. This review catalogues how metabolic modelling has advanced our understanding of the plant host and its associated microorganisms as a holobiont. We showcase how these models can contextualize heterogeneous datasets and serve as valuable tools to dissect and quantify underlying mechanisms. Finally, we consider studies that employ metabolic models as a testbed for in silico design of synthetic microbial communities with predefined traits. We conclude by discussing broader implications of the presented studies, future perspectives, and outstanding challenges.

了解植物与微生物的相互作用对于发展可持续农业做法和减轻气候变化对粮食安全的影响至关重要。植物与微生物的相互作用可以改善养分获取,减少对化肥的依赖,影响植物的健康、生长和产量,并影响植物对生物和非生物胁迫的抗性。这些相互作用主要是由代谢交换驱动的,因此可以通过代谢网络建模来理解。基因组学、宏基因组学、表型学和合成生物学的最新发展使研究人员能够在基因组尺度上利用代谢建模的潜力。在这里,我们回顾了利用基因组尺度代谢模型来研究植物-微生物在共生、致病和微生物群落系统中的相互作用的研究。本文综述了代谢模型如何促进了我们对植物寄主及其相关微生物作为全息生物的理解。我们展示了这些模型如何将异构数据集置于上下文中,并作为有价值的工具来剖析和量化底层机制。最后,我们考虑利用代谢模型作为具有预定义特征的合成微生物群落的硅设计测试平台的研究。最后,我们讨论了所提出的研究的更广泛的含义、未来的前景和突出的挑战。
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引用次数: 0
Naturally competent bacteria and their genetic parasites-a battle for control over horizontal gene transfer? 具有自然能力的细菌和它们的遗传寄生虫——一场控制水平基因转移的战斗?
IF 12.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2025-01-14 DOI: 10.1093/femsre/fuaf035
Nina Vesel, Eva Stare, Polonca Štefanič, Valentina A Floccari, Ines Mandic-Mulec, Anna Dragoš

Host-mediated natural competence for transformation of DNA and mobile genetic element (MGE)-driven conjugation and transduction are key modes of horizontal gene transfer. While these mechanisms are traditionally believed to shape bacterial evolution by enabling the acquisition of new genetic traits, numerous studies have elucidated an antagonistic relationship between natural transformation and MGEs. A new role of natural transformation as a chromosome-curing mechanism has now been proposed. Experimental data, along with mathematical models, suggest that transformation can eliminate deleterious MGEs. Supporting this hypothesis, MGEs have been shown to use various mechanisms to decrease or block transformability, such as disrupting competence genes, regulating the development of competence, hindering DNA uptake machinery, producing DNases that target the exogenous (transforming) DNA, and causing lysis of competent cells. A few examples of synergistic relationships between natural transformation and MGEs have also been reported, with natural transformation facilitating MGE transfer and phages enhancing transformation by supplying extracellular DNA through lysis and promoting competence via kin discrimination. Given the complexity of the relationships between natural transformation and MGEs, the balance between antagonism and synergy likely depends on specific selection pressures in a given context. The evidence collected here indicates a continuous conflict over horizontal gene transfer in bacteria, with semiautonomous MGEs attempting to disrupt host-controlled DNA acquisition, while host competence mechanisms work to resist MGE interference.

宿主介导的DNA转化的自然能力和移动遗传元件(MGE)驱动的偶联和转导是水平基因转移的关键模式。虽然传统上认为这些机制通过获得新的遗传性状来塑造细菌进化,但许多研究已经阐明了自然转化与MGEs之间的拮抗关系。自然转化作为染色体固化机制的新作用现已被提出。实验数据和数学模型表明,转换可以消除有害的mge。支持这一假设的是,MGEs已被证明使用各种机制来降低或阻断可转化性,例如破坏能力基因,调节能力的发展,阻碍DNA摄取机制,产生靶向外源(转化)DNA的DNA酶,以及导致可转化细胞的裂解。自然转化和MGE之间的协同关系也有一些例子被报道,自然转化促进MGE转移,噬菌体通过裂解提供细胞外DNA和通过亲缘辨别促进能力来增强转化。考虑到自然转化和MGEs之间关系的复杂性,对抗和协同之间的平衡可能取决于特定环境下的特定选择压力。本文收集的证据表明,细菌中的水平基因转移存在持续冲突,半自主的MGE试图破坏宿主控制的DNA获取,而宿主的能力机制则可以抵抗MGE的干扰。
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引用次数: 0
PROteolysis TArgeting Chimeras (PROTACs) and beyond: targeted degradation as a new path to fight microbial pathogens. 靶向嵌合体(PROTACs)及其以外的蛋白水解:靶向降解作为对抗微生物病原体的新途径。
IF 12.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2025-01-14 DOI: 10.1093/femsre/fuaf046
Alessandro Bazzacco, Beatrice Mercorelli, Arianna Loregian

Targeted degradation is emerging as a new therapeutic approach in the treatment of different diseases. It allows hijacking the cellular pathways deputed to protein or nucleic acid homeostasis to degrade a target macromolecule of interest involved in a pathogenic process. In the last decades, targeted protein degradation has been widely applied for the treatment of cancer or neurodegenerative disorders and some of such therapies are already in clinical use. More recently, therapeutic degraders such as PROTACs, LYTACs, HyTs, BacPROTACs, and others have also been explored in the field of antimicrobial and antiviral drug discovery. The peculiar mechanism of action, along with the opportunity to degrade both microbial and host targets, holds great promise for overcoming some limitations of classic antimicrobials, e.g. drug resistance, as well as for increasing the potency of current therapies. With a focus on the antimicrobial field, this Review aims at providing a comprehensive, state-of-the-art description of targeted degradation mechanisms and strategies developed so far, as well as to discuss advantages, disadvantages, and caveats of this innovative approach for combating infectious diseases.

靶向降解正在成为治疗各种疾病的一种新的治疗方法。它允许劫持代表蛋白质或核酸稳态的细胞途径,以降解涉及致病过程的目标大分子。在过去的几十年里,靶向蛋白质降解已经被广泛应用于癌症或神经退行性疾病的治疗,其中一些治疗方法已经进入临床应用。最近,治疗性降解物如PROTACs、lytac、HyTs、BacPROTACs等也在抗菌和抗病毒药物发现领域得到了探索。这种特殊的作用机制,以及降解微生物和宿主靶点的机会,为克服经典抗菌剂的一些局限性(例如耐药性)以及提高当前治疗方法的效力带来了巨大希望。以抗菌领域为重点,本综述旨在对迄今为止开发的靶向降解机制和策略进行全面、最新的描述,并讨论这种对抗传染病的创新方法的优点、缺点和注意事项。
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引用次数: 0
Resistance to last-resort antibiotics in enterococci. 肠球菌对最后手段抗生素的耐药性。
IF 12.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2025-01-14 DOI: 10.1093/femsre/fuaf057
Zhaoxiang Lu, Ross S Mclnnes, Freya Allen, Kavita Gadar, Willem van Schaik

The genus Enterococcus comprises a diverse group of species, many of which are commensal members of the gut microbiota of humans and animals. The two most prominent species associated with humans, Enterococcus faecalis and Enterococcus faecium, have also emerged as prominent opportunistic pathogens causing a range of infections in hospitalized patients, including urinary tract infections, bloodstream infections, and endocarditis. The rise of antibiotic resistance in enterococci undermines the efficacy of the treatment of infections, thus posing a significant public health risk. Enterococci readily acquire resistance to antibiotics through chromosomal mutations and the horizontal gene transfer of antibiotic resistance genes. This review offers a comprehensive examination of the mechanisms of antibiotic resistance among enterococci, with an emphasis on resistance to last-line antibiotics, including to glycopeptide antibiotics like vancomycin and teicoplanin, oxazolidinones (primarily linezolid), and daptomycin. Furthermore, we evaluate relevant candidates in the current development pipeline for antibiotics and discuss alternative strategies (phage therapy and immunotherapeutics) for the treatment and prevention of infections with multidrug-resistant enterococci. As enterococci rapidly adapt to novel conditions, including by developing resistance to new drugs and therapies, sustained research efforts are required to ensure the continuous development of treatment options for these important opportunistic pathogens.

肠球菌属包括多种多样的物种,其中许多是人类和动物肠道微生物群的共生成员。粪肠球菌和粪肠球菌是与人类相关的两种最重要的细菌,它们也已成为主要的机会致病菌,可在住院患者中引起一系列感染,包括尿路感染、血液感染和心内膜炎。肠球菌抗生素耐药性的增加破坏了治疗感染的效果,从而构成重大的公共卫生风险。肠球菌很容易通过染色体突变和抗生素耐药基因的水平基因转移获得抗生素耐药性。这篇综述提供了肠球菌抗生素耐药机制的全面研究,重点是对最后一线抗生素的耐药,包括对糖肽抗生素如万古霉素和替可普宁,恶唑烷酮(主要是利奈唑胺)和达托霉素的耐药。此外,我们评估了目前正在开发的相关候选抗生素,并讨论了治疗和预防多重耐药肠球菌感染的替代策略(噬菌体疗法和免疫疗法)。随着肠球菌迅速适应新环境,包括对新药物和新疗法产生耐药性,需要持续的研究努力,以确保不断开发针对这些重要机会性病原体的治疗方案。
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引用次数: 0
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