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Methanobactins: Structures, Biosynthesis, and Microbial Diversity. 甲烷菌素:结构、生物合成和微生物多样性。
IF 8.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-08-09 DOI: 10.1146/annurev-micro-041522-092911
Reyvin M Reyes, Amy C Rosenzweig

Methanobactins (Mbns) are ribosomally synthesized and posttranslationally modified peptide natural products released by methanotrophic bacteria under conditions of copper scarcity. Mbns bind Cu(I) with high affinity via nitrogen-containing heterocycles and thioamide groups installed on a precursor peptide, MbnA, by a core biosynthetic enzyme complex, MbnBC. Additional stabilizing modifications are enacted by other, less universal biosynthetic enzymes. Copper-loaded Mbn is imported into the cell by TonB-dependent transporters called MbnTs, and copper is mobilized by an unknown mechanism. The machinery to biosynthesize and transport Mbn is encoded in operons that are also found in the genomes of nonmethanotrophic bacteria. In this review, we provide an update on the state of the Mbn field, highlighting recent discoveries regarding Mbn structure, biosynthesis, and handling as well as the emerging roles of Mbns in the environment and their potential use as therapeutics.

甲烷菌素(Mbns)是甲烷营养细菌在缺铜条件下通过核糖体合成并经翻译后修饰的多肽天然产物。Mbns 通过核心生物合成酶复合物 MbnBC 在前体肽 MbnA 上安装的含氮杂环和硫酰胺基团与铜(I)结合,具有很高的亲和力。其他通用性较低的生物合成酶会对其进行额外的稳定修饰。含铜的 Mbn 由称为 MbnTs 的依赖 TonB 的转运体输入细胞,铜则通过一种未知的机制被调动起来。生物合成和运输 Mbn 的机制由操作子编码,这些操作子也存在于非甲烷营养细菌的基因组中。在这篇综述中,我们将介绍 Mbn 领域的最新进展,重点介绍有关 Mbn 结构、生物合成和处理的最新发现,以及 Mbns 在环境中的新作用及其作为治疗药物的潜在用途。
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引用次数: 0
Innovative Strategies to Study the Pathogenesis of Elusive Spirochetes and Difficulties Managing the Chronic Infections They Cause. 研究难以捉摸的螺旋体致病机理的创新战略及其导致的慢性感染的管理难题。
IF 8.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-08-06 DOI: 10.1146/annurev-micro-100423-030847
Mohamed Abdallah Mohamed Moustafa, Samantha Schlachter, Nikhat Parveen

The major human spirochetal pathogens (Leptospira, Borrelia, and Treponema) are difficult to diagnose and lack vaccines to prevent infections. Infection by these spirochetes does not generate general protective immunity, allowing reinfection by different strains to occur. These stealth pathogens have uncommon physiology, pathogenesis, and clinical presentations and possess unique immune evasion mechanisms to facilitate their host adaptation and persistence. Collectively, host-spirochete interactions orchestrate systemic infections in a manner distinct from organ- and tissue-specific diseases caused by many bacterial pathogens. Difficulties in growing and genetic manipulation of infectious spirochetes have hindered the full understanding of their virulence factors despite decades to centuries of research. This article highlights the current understanding of the intricacies of spirochetal pathogenesis and diseases. Our comprehensive review of the progress versus gaps in knowledge lays a foundation for researchers to direct their studies toward the development of effective diagnostics and vaccines to protect patients from serious, chronic spirochetal diseases.

主要的人类螺旋体病原体(钩端螺旋体、鲍氏螺旋体和特雷波尼马螺旋体)很难诊断,也缺乏预防感染的疫苗。感染这些螺旋体不会产生普遍的保护性免疫,从而导致不同菌株的再感染。这些隐形病原体具有不常见的生理、发病机制和临床表现,并拥有独特的免疫逃避机制,以促进宿主的适应性和持久性。总之,宿主与螺旋体之间的相互作用协调了全身感染,其方式有别于许多细菌病原体引起的器官和组织特异性疾病。尽管已经进行了几十年甚至上百年的研究,但传染性螺旋体的生长和遗传操作困难阻碍了人们对其毒力因子的全面了解。本文重点介绍了目前对螺旋体致病机理和疾病复杂性的理解。我们对研究进展和知识差距的全面回顾为研究人员奠定了基础,有助于他们将研究方向转向开发有效的诊断方法和疫苗,保护患者免受严重慢性螺旋体疾病的侵害。
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引用次数: 0
Cytoskeleton Organization in Formation and Motility of Apicomplexan Parasites. 寄生虫形成和运动过程中的细胞骨架组织
IF 8.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-08-02 DOI: 10.1146/annurev-micro-041222-011539
Ross G Douglas, Robert W Moon, Friedrich Frischknecht

Apicomplexan parasites are a group of eukaryotic protozoans with diverse biology that have affected human health like no other group of parasites. These obligate intracellular parasites rely on their cytoskeletal structures for giving them form, enabling them to replicate in unique ways and to migrate across tissue barriers. Recent progress in transgenesis and imaging tools allowed detailed insights into the components making up and regulating the actin and microtubule cytoskeleton as well as the alveolate-specific intermediate filament-like cytoskeletal network. These studies revealed interesting details that deviate from the cell biology of canonical model organisms. Here we review the latest developments in the field and point to a number of open questions covering the most experimentally tractable parasites: Plasmodium, the causative agent of malaria; Toxoplasma gondii, the causative agent of toxoplasmosis; and Cryptosporidium, a major cause of diarrhea.

表皮复合寄生虫是一类具有多种生物学特性的真核原生动物,对人类健康的影响是其他寄生虫无法比拟的。这些必须在细胞内寄生的寄生虫依靠细胞骨架结构赋予它们形态,使它们能够以独特的方式复制并跨越组织屏障迁移。最近在转基因和成像工具方面取得的进展使人们能够详细了解组成和调节肌动蛋白和微管细胞骨架的成分,以及肺泡特异性中间丝状细胞骨架网络。这些研究揭示了与典型模式生物的细胞生物学不同的有趣细节。在此,我们回顾了该领域的最新进展,并指出了一些涉及最易实验的寄生虫的开放性问题:疟原虫,疟疾的病原体;弓形虫,弓形虫病的病原体;以及隐孢子虫,腹泻的主要病原体。
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引用次数: 0
Apicomplexan Pore-Forming Toxins. 吸虫毛孔形成毒素
IF 8.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-08-01 DOI: 10.1146/annurev-micro-041222-025939
Vern B Carruthers

Pore-forming toxins (PFTs) are released by one cell to directly inflict damage on another cell. Hosts use PFTs, including members of the membrane attack complex/perforin protein family, to fight bacterial infections and cancer, while bacteria and parasites deploy PFTs to promote infection. Apicomplexan parasites secrete perforin-like proteins as PFTs to egress from infected cells and traverse tissue barriers. Other protozoa, along with helminth parasites, utilize saposin-like PFTs prospectively for nutrient acquisition during infection. This review discusses seminal and more recent advances in understanding how parasite PFTs promote infection and describes how they are regulated and fulfill their roles without causing parasite self-harm. Although exciting progress has been made in defining mechanisms of pore formation by PFTs, many open questions remain to be addressed to gain additional key insights into these remarkable determinants of parasitic infections.

孔形成毒素(PFT)由一个细胞释放,直接对另一个细胞造成损害。宿主利用孔形成毒素(包括膜攻击复合体/穿孔素蛋白家族成员)来对抗细菌感染和癌症,而细菌和寄生虫则利用孔形成毒素来促进感染。吸虫类寄生虫分泌穿孔素样蛋白作为 PFT,以从受感染细胞中排出并穿越组织屏障。其他原生动物和蠕虫寄生虫则在感染过程中利用类沙波素 PFT 获取营养。本综述讨论了在了解寄生虫 PFT 如何促进感染方面的开创性进展和最新进展,并介绍了如何在不造成寄生虫自我伤害的情况下调节和发挥它们的作用。尽管在确定 PFTs 孔隙形成机制方面取得了令人振奋的进展,但要深入了解这些决定寄生虫感染的重要因素,仍有许多悬而未决的问题有待解决。
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引用次数: 0
Nucleotide Immune Signaling in CBASS, Pycsar, Thoeris, and CRISPR Antiphage Defense. CBASS、Pycsar、Thoeris 和 CRISPR 反虹吸防御中的核苷酸免疫信号转导。
IF 8.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-31 DOI: 10.1146/annurev-micro-041222-024843
Samuel J Hobbs, Philip J Kranzusch

Bacteria encode an arsenal of diverse systems that defend against phage infection. A common theme uniting many prevalent antiphage defense systems is the use of specialized nucleotide signals that function as second messengers to activate downstream effector proteins and inhibit viral propagation. In this article, we review the molecular mechanisms controlling nucleotide immune signaling in four major families of antiphage defense systems: CBASS, Pycsar, Thoeris, and type III CRISPR immunity. Analyses of the individual steps connecting phage detection, nucleotide signal synthesis, and downstream effector function reveal shared core principles of signaling and uncover system-specific strategies used to augment immune defense. We compare recently discovered mechanisms used by phages to evade nucleotide immune signaling and highlight convergent strategies that shape host-virus interactions. Finally, we explain how the evolutionary connection between bacterial antiphage defense and eukaryotic antiviral immunity defines fundamental rules that govern nucleotide-based immunity across all kingdoms of life.

细菌编码了一系列不同的系统来抵御噬菌体感染。许多流行的抗噬菌体防御系统的一个共同主题是利用专门的核苷酸信号作为第二信使激活下游效应蛋白并抑制病毒传播。在这篇文章中,我们回顾了四大抗虹吸虫防御系统家族中控制核苷酸免疫信号转导的分子机制:CBASS、Pycsar、Thoeris 和 III 型 CRISPR 免疫。通过分析连接噬菌体检测、核苷酸信号合成和下游效应器功能的各个步骤,我们发现了信号传递的共同核心原理,并揭示了用于增强免疫防御的系统特异性策略。我们比较了最近发现的噬菌体用于规避核苷酸免疫信号的机制,并强调了形成宿主-病毒相互作用的趋同策略。最后,我们解释了细菌抗噬菌体防御与真核生物抗病毒免疫之间的进化联系如何定义了所有生命王国基于核苷酸的免疫的基本规则。
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引用次数: 0
Molecular Mechanisms for Iron Uptake and Homeostasis in Marine Eukaryotic Phytoplankton. 海洋真核浮游植物铁吸收和平衡的分子机制。
IF 8.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-17 DOI: 10.1146/annurev-micro-041222-023252
Robert H Lampe, Tyler H Coale, Jeffrey B McQuaid, Andrew E Allen

The micronutrient iron is essential for phytoplankton growth due to its central role in a wide variety of key metabolic processes including photosynthesis and nitrate assimilation. As a result of scarce bioavailable iron in seawater, marine primary productivity is often iron-limited with future iron supplies remaining uncertain. Although evolutionary constraints resulted in high cellular iron requirements, phytoplankton evolved diverse mechanisms that enable uptake of multiple forms of iron, storage of iron over short and long timescales, and modulation of their iron requirement under stress. Genomics continues to increase our understanding of iron-related proteins that are homologous to those characterized in other model organisms, while recently, molecular and cell biology is revealing unique genes and processes with connections to iron acquisition or use. Moreover, there are an increasing number of examples showing the interplay between iron uptake and extracellular processes such as boundary layer chemistry and microbial interactions.

微量营养元素铁是浮游植物生长所必需的,因为它在光合作用和硝酸盐同化作用等多种关键代谢过程中发挥着核心作用。由于海水中生物可利用的铁稀缺,海洋初级生产力往往受到铁的限制,而且未来的铁供应仍不确定。虽然进化限制导致细胞对铁的需求量很高,但浮游植物进化出了多种机制,能够吸收多种形式的铁、在短时间和长时间内储存铁以及在压力下调节对铁的需求。基因组学不断加深我们对与铁有关的蛋白质的了解,这些蛋白质与其他模式生物中的蛋白质具有同源性,而最近,分子和细胞生物学正在揭示与铁的获取或使用有关的独特基因和过程。此外,越来越多的实例显示了铁吸收与细胞外过程(如边界层化学和微生物相互作用)之间的相互作用。
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引用次数: 0
When the Host Encounters the Cell Wall and Vice Versa. 当宿主遇到细胞壁,反之亦然。
IF 8.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-17 DOI: 10.1146/annurev-micro-041522-094053
Kelvin Kho, Thimoro Cheng, Nienke Buddelmeijer, Ivo G Boneca

Peptidoglycan (PGN) and associated surface structures such as secondary polymers and capsules have a central role in the physiology of bacteria. The exoskeletal PGN heteropolymer is the major determinant of cell shape and allows bacteria to withstand cytoplasmic turgor pressure. Thus, its assembly, expansion, and remodeling during cell growth and division need to be highly regulated to avoid compromising cell survival. Similarly, regulation of the assembly impacts bacterial cell shape; distinct shapes enhance fitness in different ecological niches, such as the host. Because bacterial cell wall components, in particular PGN, are exposed to the environment and unique to bacteria, these have been coopted during evolution by eukaryotes to detect bacteria. Furthermore, the essential role of the cell wall in bacterial survival has made PGN an important signaling molecule in the dialog between host and microbes and a target of many host responses. Millions of years of coevolution have resulted in a pivotal role for PGN fragments in shaping host physiology and in establishing a long-lasting symbiosis between microbes and the host. Thus, perturbations of this dialog can lead to pathologies such as chronic inflammatory diseases. Similarly, pathogens have devised sophisticated strategies to manipulate the system to enhance their survival and growth.

肽聚糖(PGN)和相关的表面结构(如次生聚合物和胶囊)在细菌的生理学中起着核心作用。外骨骼 PGN 杂聚合物是细胞形状的主要决定因素,可使细菌承受细胞质的张力压力。因此,在细胞生长和分裂过程中,需要对其组装、扩展和重塑进行高度调控,以避免影响细胞存活。同样,对组装的调控也会影响细菌细胞的形状;不同的形状会提高在不同生态位(如宿主)中的适应性。由于细菌细胞壁成分(尤其是 PGN)暴露在环境中,而且是细菌独有的,因此真核生物在进化过程中利用这些成分来检测细菌。此外,细胞壁在细菌生存中的重要作用使 PGN 成为宿主与微生物之间对话的重要信号分子,并成为许多宿主反应的目标。经过数百万年的共同进化,PGN 片段在塑造宿主生理机能以及在微生物与宿主之间建立长期共生关系方面发挥了关键作用。因此,如果这种对话受到干扰,就会导致慢性炎症等病症。同样,病原体也设计了复杂的策略来操纵这一系统,以提高它们的生存和生长。
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引用次数: 0
Periplasmic Chaperones: Outer Membrane Biogenesis and Envelope Stress. 外膜伴侣蛋白:外膜生物生成与包膜压力
IF 8.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-15 DOI: 10.1146/annurev-micro-041522-102901
Ashton N Combs, Thomas J Silhavy

Envelope biogenesis and homeostasis in gram-negative bacteria are exceptionally intricate processes that require a multitude of periplasmic chaperones to ensure cellular survival. Remarkably, these chaperones perform diverse yet specialized functions entirely in the absence of external energy such as ATP, and as such have evolved sophisticated mechanisms by which their activities are regulated. In this article, we provide an overview of the predominant periplasmic chaperones that enable efficient outer membrane biogenesis and envelope homeostasis in Escherichia coli. We also discuss stress responses that act to combat unfolded protein stress within the cell envelope, highlighting the periplasmic chaperones involved and the mechanisms by which envelope homeostasis is restored.

革兰氏阴性细菌的包膜生物生成和平衡是一个异常复杂的过程,需要大量的外质合体来确保细胞存活。值得注意的是,这些合体完全是在缺乏 ATP 等外部能量的情况下执行各种特殊功能的,因此它们的活动受到了复杂机制的调控。在本文中,我们将概述大肠杆菌中实现高效外膜生物生成和包膜稳态的主要外质合体。我们还讨论了在细胞包膜内对抗未折叠蛋白应激的应激反应,重点介绍了所涉及的外质合体以及恢复包膜平衡的机制。
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引用次数: 0
From Chaos Comes Order: Genetics and Genome Biology of Arbuscular Mycorrhizal Fungi. 从混沌到有序:丛枝菌根真菌的遗传学和基因组生物学》。
IF 8.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-10 DOI: 10.1146/annurev-micro-041522-105143
Jordana Oliveira, Gokalp Yildirir, Nicolas Corradi

Arbuscular mycorrhizal fungi (AMF) are obligate mutualists that can enhance nutrition and growth of their plant hosts while providing protection against pathogens. AMF produce spores and hyphal networks that can carry thousands of nuclei in a continuous cytoplasm, with no evidence of sexual reproduction. This review examines the impact of genomic technologies on our view of AMF genetics and evolution. We highlight how the genetics, nuclear dynamics, and epigenetics of these prominent symbionts follow trends preserved in distant multinucleate fungal relatives. We also propose new avenues of research to improve our understanding of their nuclear biology and their intricate genetic interactions with plant hosts.

丛枝菌根真菌(AMF)是一种必须互生的真菌,可以增强植物宿主的营养和生长,同时还能抵御病原体的侵袭。丛枝菌根真菌产生孢子和菌丝网络,可在连续的细胞质中携带数千个细胞核,但没有有性生殖的迹象。本综述探讨了基因组技术对我们了解 AMF 遗传学和进化的影响。我们强调了这些重要共生体的遗传学、核动力学和表观遗传学是如何追随遥远的多核真菌近亲所保留的趋势的。我们还提出了新的研究途径,以增进我们对它们的核生物学及其与植物宿主之间错综复杂的遗传相互作用的了解。
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引用次数: 0
Unpacking Alternative Features of the Bacterial Chemotaxis System. 解读细菌趋化系统的另类特征
IF 8.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-10 DOI: 10.1146/annurev-micro-032421-110850
A R Muok, F A Olsthoorn, A Briegel

The bacterial chemotaxis system is one of the best-understood cellular pathways and serves as the model for signal transduction systems. Most chemotaxis research has been conducted with transmembrane chemotaxis systems from Escherichia coli and has established paradigms of the system that were thought to be universal. However, emerging research has revealed that many bacteria possess alternative features of their chemotaxis system, demonstrating that these systems are likely more complex than previously assumed. Here, we compare the canonical chemotaxis system of E. coli with systems that diverge in supramolecular architecture, sensory mechanisms, and protein composition. The alternative features have likely evolved to accommodate chemical specificities of natural niches and cell morphologies. Collectively, these studies demonstrate that bacterial chemotaxis systems are a rapidly expanding field that offers many new opportunities to explore this exceedingly diverse system.

细菌趋化系统是最容易理解的细胞通路之一,也是信号转导系统的模型。大多数趋化研究都是利用大肠杆菌的跨膜趋化系统进行的,并建立了被认为是通用的系统范例。然而,新的研究发现,许多细菌的趋化系统具有其他特征,这表明这些系统可能比以前假设的更为复杂。在这里,我们将大肠杆菌的典型趋化系统与在超分子结构、感觉机制和蛋白质组成方面存在差异的系统进行了比较。这些不同的特征很可能是为了适应自然壁龛和细胞形态的化学特异性而进化而来的。这些研究共同表明,细菌趋化系统是一个迅速扩展的领域,为探索这一极其多样化的系统提供了许多新的机会。
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引用次数: 0
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Annual review of microbiology
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