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Small RNAs, Large Networks: Posttranscriptional Regulons in Gram-Negative Bacteria. 小RNA,大网络:革兰氏阴性菌中的转录后调控子。
IF 10.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2023-09-15 Epub Date: 2023-03-21 DOI: 10.1146/annurev-micro-041320-025836
Kai Papenfort, Sahar Melamed

Small regulatory RNA (sRNAs) are key mediators of posttranscriptional gene control in bacteria. Assisted by RNA-binding proteins, a single sRNA often modulates the expression of dozens of genes, and thus sRNAs frequently adopt central roles in regulatory networks. Posttranscriptional regulation by sRNAs comes with several unique features that cannot be achieved by transcriptional regulators. However, for optimal network performance, transcriptional and posttranscriptional control mechanisms typically go hand-in-hand. This view is reflected by the ever-growing class of mixed network motifs involving sRNAs and transcription factors, which are ubiquitous in biology and whose regulatory properties we are beginning to understand. In addition, sRNA activity can be antagonized by base-pairing with sponge RNAs, adding yet another layer of complexity to these networks. In this article, we summarize the regulatory concepts underlying sRNA-mediated gene control in bacteria and discuss how sRNAs shape the output of a network, focusing on several key examples.

小调节RNA(sRNA)是细菌转录后基因控制的关键介质。在RNA结合蛋白的协助下,单个sRNA通常调节数十个基因的表达,因此sRNA经常在调节网络中发挥核心作用。sRNA的转录后调节具有转录调节因子无法实现的几个独特特征。然而,为了获得最佳的网络性能,转录和转录后控制机制通常是齐头并进的。这一观点反映在越来越多的涉及sRNA和转录因子的混合网络基序中,它们在生物学中无处不在,我们开始了解它们的调控特性。此外,sRNA活性可以通过与海绵RNA的碱基配对来拮抗,这为这些网络增加了另一层复杂性。在这篇文章中,我们总结了sRNA介导的细菌基因控制的调控概念,并讨论了sRNA如何塑造网络的输出,重点讨论了几个关键的例子。
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引用次数: 13
Past, Present, and Future of Extracytoplasmic Function σ Factors: Distribution and Regulatory Diversity of the Third Pillar of Bacterial Signal Transduction. 胞外功能σ因子的过去、现在和未来:细菌信号转导第三支柱的分布和调节多样性。
IF 10.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2023-09-15 Epub Date: 2023-07-12 DOI: 10.1146/annurev-micro-032221-024032
Thorsten Mascher

Responding to environmental cues is a prerequisite for survival in the microbial world. Extracytoplasmic function σ factors (ECFs) represent the third most abundant and by far the most diverse type of bacterial signal transduction. While archetypal ECFs are controlled by cognate anti-σ factors, comprehensive comparative genomics efforts have revealed a much higher abundance and regulatory diversity of ECF regulation than previously appreciated. They have also uncovered a diverse range of anti-σ factor-independent modes of controlling ECF activity, including fused regulatory domains and phosphorylation-dependent mechanisms. While our understanding of ECF diversity is comprehensive for well-represented and heavily studied bacterial phyla-such as Proteobacteria, Firmicutes, and Actinobacteria (phylum Actinomycetota)-our current knowledge about ECF-dependent signaling in the vast majority of underrepresented phyla is still far from complete. In particular, the dramatic extension of bacterial diversity in the course of metagenomic studies represents both a new challenge and an opportunity in expanding the world of ECF-dependent signal transduction.

对环境线索的反应是在微生物世界中生存的先决条件。胞外功能σ因子(ECFs)代表了第三丰富和迄今为止最多样化的细菌信号转导类型。虽然原型ECF由同源抗σ因子控制,但全面的比较基因组学研究表明,ECF调节的丰度和调节多样性比以前所认识的要高得多。他们还发现了多种与抗σ因子无关的控制ECF活性的模式,包括融合的调节结构域和磷酸化依赖性机制。虽然我们对ECF多样性的理解是全面的,适用于有代表性和大量研究的细菌门,如变形菌门、厚壁菌门和放线菌门(放线菌纲),但我们目前对绝大多数代表性不足的门的ECF依赖性信号传导的了解仍远未完成。特别是,在宏基因组研究过程中,细菌多样性的显著扩展代表了扩大ECF依赖性信号转导世界的新挑战和机遇。
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引用次数: 2
Mobile Genetic Element Flexibility as an Underlying Principle to Bacterial Evolution. 可移动遗传元件的灵活性是细菌进化的基本原理。
IF 10.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2023-09-15 Epub Date: 2023-07-12 DOI: 10.1146/annurev-micro-032521-022006
Alexandra J Weisberg, Jeff H Chang

Mobile genetic elements are key to the evolution of bacteria and traits that affect host and ecosystem health. Here, we use a framework of a hierarchical and modular system that scales from genes to populations to synthesize recent findings on mobile genetic elements (MGEs) of bacteria. Doing so highlights the role that emergent properties of flexibility, robustness, and genetic capacitance of MGEs have on the evolution of bacteria. Some of their traits can be stored, shared, and diversified across different MGEs, taxa of bacteria, and time. Collectively, these properties contribute to maintaining functionality against perturbations while allowing changes to accumulate in order to diversify and give rise to new traits. These properties of MGEs have long challenged our abilities to study them. Implementation of new technologies and strategies allows for MGEs to be analyzed in new and powerful ways.

可移动的遗传元素是影响宿主和生态系统健康的细菌和性状进化的关键。在这里,我们使用了一个从基因到种群的分层和模块化系统的框架来综合细菌的移动遗传元件(MGE)的最新发现。这样做突出了MGE的灵活性、稳健性和遗传容量等新兴特性对细菌进化的作用。它们的一些特征可以在不同的MGE、细菌分类群和时间内存储、共享和多样化。总的来说,这些特性有助于保持抵抗扰动的功能,同时允许变化积累,以实现多样化并产生新的特征。MGE的这些特性长期以来一直对我们研究它们的能力提出挑战。新技术和战略的实施使MGE能够以新的、强大的方式进行分析。
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引用次数: 3
Essential Amino Acid Metabolites as Chemical Mediators of Host-Microbe Interaction in the Gut. 必需氨基酸代谢产物作为肠道中宿主-微生物相互作用的化学介质。
IF 8.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2023-09-15 Epub Date: 2023-06-20 DOI: 10.1146/annurev-micro-032421-111819
Jessica R McCann, John F Rawls

Amino acids are indispensable substrates for protein synthesis in all organisms and incorporated into diverse aspects of metabolic physiology and signaling. However, animals lack the ability to synthesize several of them and must acquire these essential amino acids from their diet or perhaps their associated microbial communities. The essential amino acids therefore occupy a unique position in the health of animals and their relationships with microbes. Here we review recent work connecting microbial production and metabolism of essential amino acids to host biology, and the reciprocal impacts of host metabolism of essential amino acids on their associated microbes. We focus on the roles of the branched-chain amino acids (valine, leucine, and isoleucine) and tryptophan on host-microbe communication in the intestine of humans and other vertebrates. We then conclude by highlighting research questions surrounding the less-understood aspects of microbial essential amino acid synthesis in animal hosts.

氨基酸是所有生物体中蛋白质合成不可或缺的底物,并被纳入代谢生理学和信号传导的各个方面。然而,动物缺乏合成其中几种氨基酸的能力,必须从饮食或相关微生物群落中获得这些必需氨基酸。因此,必需氨基酸在动物的健康及其与微生物的关系中占有独特的地位。在这里,我们回顾了最近将微生物生产和必需氨基酸代谢与宿主生物学联系起来的工作,以及宿主必需氨基酸代谢对其相关微生物的相互影响。我们重点研究了支链氨基酸(缬氨酸、亮氨酸和异亮氨酸)和色氨酸在人类和其他脊椎动物肠道中宿主-微生物交流中的作用。最后,我们强调了围绕动物宿主中微生物必需氨基酸合成的鲜为人知的方面的研究问题。
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引用次数: 0
The ChvG-ChvI Regulatory Network: A Conserved Global Regulatory Circuit Among the Alphaproteobacteria with Pervasive Impacts on Host Interactions and Diverse Cellular Processes. ChvG-ChvI调控网络:对宿主相互作用和多种细胞过程具有普遍影响的α-变形菌中的一个保守的全球调控回路。
IF 10.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2023-09-15 Epub Date: 2023-04-11 DOI: 10.1146/annurev-micro-120822-102714
Jennifer L Greenwich, Brynn C Heckel, Melene A Alakavuklar, Clay Fuqua

The ChvG-ChvI two-component system is conserved among multiple Alphaproteobacteria. ChvG is a canonical two-component system sensor kinase with a single large periplasmic loop. Active ChvG directs phosphotransfer to its cognate response regulator ChvI, which controls transcription of target genes. In many alphaproteobacteria, ChvG is regulated by a third component, a periplasmic protein called ExoR, that maintains ChvG in an inactive state through direct interaction. Acidic pH stimulates proteolysis of ExoR, unfettering ChvG-ChvI to control its regulatory targets. Activated ChvI among different alphaproteobacteria controls a broad range of cellular processes, including symbiosis and virulence, exopolysaccharide production, biofilm formation, motility, type VI secretion, cellular metabolism, envelope composition, and growth. Low pH is a virulence signal in Agrobacterium tumefaciens, but in other systems, conditions that cause envelope stress may also generally activate ChvG-ChvI. There is mounting evidence that these regulators influence diverse aspects of bacterial physiology, including but not limited to host interactions.

ChvG-ChvI双组分系统在多种α蛋白细菌中是保守的。ChvG是一种典型的双组分系统传感器激酶,具有单个大周质环。活性ChvG将磷酸转移导向其同源反应调节因子ChvI,后者控制靶基因的转录。在许多α蛋白细菌中,ChvG由第三种成分调节,即一种称为ExoR的周质蛋白,通过直接相互作用使ChvG保持在非活性状态。酸性pH刺激ExoR的蛋白水解,使ChvG-ChvI无法控制其调节靶标。不同α变形菌之间激活的ChvI控制着广泛的细胞过程,包括共生和毒力、胞外多糖产生、生物膜形成、运动性、VI型分泌、细胞代谢、包膜组成和生长。低pH是根癌农杆菌的毒力信号,但在其他系统中,引起包膜应激的条件通常也可能激活ChvG-ChvI。越来越多的证据表明,这些调节因子影响细菌生理学的各个方面,包括但不限于宿主的相互作用。
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引用次数: 2
Are Bacteria Leaky? Mechanisms of Metabolite Externalization in Bacterial Cross-Feeding. 细菌泄漏吗?细菌交叉喂养中代谢产物外部化的机制。
IF 10.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2023-09-15 Epub Date: 2023-06-07 DOI: 10.1146/annurev-micro-032521-023815
James B McKinlay

The metabolism of a bacterial cell stretches beyond its boundaries, often connecting with the metabolism of other cells to form extended metabolic networks that stretch across communities, and even the globe. Among the least intuitive metabolic connections are those involving cross-feeding of canonically intracellular metabolites. How and why are these intracellular metabolites externalized? Are bacteria simply leaky? Here I consider what it means for a bacterium to be leaky, and I review mechanisms of metabolite externalization from the context of cross-feeding. Despite common claims, diffusion of most intracellular metabolites across a membrane is unlikely. Instead, passive and active transporters are likely involved, possibly purging excess metabolites as part of homeostasis. Re-acquisition of metabolites by a producer limits the opportunities for cross-feeding. However, a competitive recipient can stimulate metabolite externalization and initiate a positive-feedback loop of reciprocal cross-feeding.

细菌细胞的新陈代谢超出了它的边界,通常与其他细胞的新陈代谢联系在一起,形成延伸到整个社区甚至全球的代谢网络。最不直观的代谢联系是那些涉及经典细胞内代谢产物的交叉喂养。这些细胞内代谢物是如何以及为什么外化的?细菌只是渗漏吗?在这里,我考虑了细菌渗漏的含义,并从交叉喂养的角度回顾了代谢物外化的机制。尽管有常见的说法,但大多数细胞内代谢物不太可能通过膜扩散。相反,被动和主动转运蛋白可能参与其中,可能作为体内平衡的一部分清除多余的代谢产物。生产者重新获取代谢产物限制了交叉喂养的机会。然而,竞争性受体可以刺激代谢物外化,并启动相互交叉喂养的正反馈回路。
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引用次数: 3
License to Clump: Secretory IgA Structure-Function Relationships Across Scales. Clump许可证:跨量表的分泌IgA结构-功能关系。
IF 10.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2023-09-15 DOI: 10.1146/annurev-micro-032521-041803
Alyson Hockenberry, Emma Slack, Beth M Stadtmueller

Secretory antibodies are the only component of our adaptive immune system capable of attacking mucosal pathogens topologically outside of our bodies. All secretory antibody classes are (a) relatively resistant to harsh proteolytic environments and (b) polymeric. Recent elucidation of the structure of secretory IgA (SIgA) has begun to shed light on SIgA functions at the nanoscale. We can now begin to unravel the structure-function relationships of these molecules, for example, by understanding how the bent conformation of SIgA enables robust cross-linking between adjacent growing bacteria. Many mysteries remain, such as the structural basis of protease resistance and the role of noncanonical bacteria-IgA interactions. In this review, we explore the structure-function relationships of IgA from the nano- to the metascale, with a strong focus on how the seemingly banal "license to clump" can have potent effects on bacterial physiology and colonization.

分泌性抗体是我们适应性免疫系统中唯一能够在体外从拓扑结构上攻击粘膜病原体的成分。所有分泌型抗体类别(a)对恶劣的蛋白水解环境具有相对抗性,(b)是聚合物。最近对分泌型IgA(SIgA)结构的阐明已经开始揭示SIgA在纳米尺度上的功能。我们现在可以开始解开这些分子的结构-功能关系,例如,通过了解SIgA的弯曲构象如何在相邻生长的细菌之间实现强大的交联。许多谜团仍然存在,例如蛋白酶抗性的结构基础和非经典细菌IgA相互作用的作用。在这篇综述中,我们探索了IgA从纳米到超尺度的结构-功能关系,重点是看似平庸的“结块许可”如何对细菌生理和定植产生强大影响。
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引用次数: 0
Factors Affecting Variation of the Human Gut Phageome. 影响人类肠道形态变异的因素。
IF 10.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2023-09-15 Epub Date: 2023-07-12 DOI: 10.1146/annurev-micro-032421-105754
Ciara A Tobin, Colin Hill, Andrey N Shkoporov

The gut microbiome is a dense and metabolically active consortium of microorganisms and viruses located in the lower gastrointestinal tract of the human body. Bacteria and their viruses (phages) are the most abundant members of the gut microbiome. Investigating their biology and the interplay between the two is important if we are to understand their roles in human health and disease. In this review, we summarize recent advances in resolving the taxonomic structure and ecological functions of the complex community of phages in the human gut-the gut phageome. We discuss how age, diet, and geography can all have a significant impact on phageome composition. We note that alterations to the gut phageome have been observed in several diseases such as inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer, and we evaluate whether these phageome changes can directly or indirectly contribute to disease etiology and pathogenesis. We also highlight how lack of standardization in studying the gut phageome has contributed to variation in reported results.

肠道微生物组是位于人体下消化道的微生物和病毒的密集且代谢活跃的群落。细菌及其病毒(噬菌体)是肠道微生物组中最丰富的成员。如果我们想了解它们在人类健康和疾病中的作用,研究它们的生物学及其相互作用是很重要的。在这篇综述中,我们总结了在解决人类肠道中复杂噬菌体群落(肠道吞噬组)的分类结构和生态功能方面的最新进展。我们讨论了年龄、饮食和地理因素如何对吞噬组的组成产生重大影响。我们注意到,在炎症性肠病、肠易激综合征和结直肠癌癌症等多种疾病中观察到肠道吞噬组的改变,我们评估这些吞噬组的变化是否会直接或间接导致疾病的病因和发病机制。我们还强调了肠道吞噬组研究缺乏标准化是如何导致报告结果变化的。
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引用次数: 2
TonB-Dependent Transport Across the Bacterial Outer Membrane. TonB依赖性细菌外膜转运。
IF 10.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2023-09-15 Epub Date: 2023-03-21 DOI: 10.1146/annurev-micro-032421-111116
Augustinas Silale, Bert van den Berg

TonB-dependent transporters (TBDTs) are present in all gram-negative bacteria and mediate energy-dependent uptake of molecules that are too scarce or large to be taken up efficiently by outer membrane (OM) diffusion channels. This process requires energy that is derived from the proton motive force and delivered to TBDTs by the TonB-ExbBD motor complex in the inner membrane. Together with the need to preserve the OM permeability barrier, this has led to an extremely complex and fascinating transport mechanism for which the fundamentals, despite decades of research, are still unclear. In this review, we describe our current understanding of the transport mechanism of TBDTs, their potential role in the delivery of novel antibiotics, and the important contributions made by TBDT-associated (lipo)proteins.

TonB依赖性转运蛋白(TBDT)存在于所有革兰氏阴性菌中,并介导对分子的能量依赖性摄取,这些分子太少或太大,无法被外膜(OM)扩散通道有效吸收。这一过程需要来自质子原动力的能量,并通过内膜中的TonB-ExbBD马达复合体输送到TBDT。再加上需要保护OM渗透屏障,这导致了一种极其复杂和迷人的传输机制,尽管进行了几十年的研究,但其基本原理仍不清楚。在这篇综述中,我们描述了我们目前对TBDT转运机制的理解,它们在新型抗生素递送中的潜在作用,以及TBDT相关(脂)蛋白的重要贡献。
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引用次数: 5
The Origin of Metazoan Multicellularity: A Potential Microbial Black Swan Event. 后生动物多细胞性的起源:一个潜在的微生物黑天鹅事件。
IF 10.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2023-09-15 Epub Date: 2023-07-05 DOI: 10.1146/annurev-micro-032421-120023
Iñaki Ruiz-Trillo, Koryu Kin, Elena Casacuberta

The emergence of animals from their unicellular ancestors is a major evolutionary event. Thanks to the study of diverse close unicellular relatives of animals, we now have a better grasp of what the unicellular ancestor of animals was like. However, it is unclear how that unicellular ancestor of animals became the first animals. To explain this transition, two popular theories, the choanoblastaea and the synzoospore, have been proposed. We will revise and expose the flaws in these two theories while showing that, due to the limits of our current knowledge, the origin of animals is a biological black swan event. As such, the origin of animals defies retrospective explanations. Therefore, we should be extra careful not to fall for confirmation biases based on few data and, instead, embrace this uncertainty and be open to alternative scenarios. With the aim to broaden the potential explanations on how animals emerged, we here propose two novel and alternative scenarios. In any case, to find the answer to how animals evolved, additional data will be required, as will the hunt for microscopic creatures that are closely related to animals but have not yet been sampled and studied.

动物从单细胞祖先那里出现是一个重大的进化事件。由于对动物的各种单细胞近亲的研究,我们现在对动物的单细胞祖先有了更好的了解。然而,尚不清楚动物的单细胞祖先是如何成为第一批动物的。为了解释这种转变,人们提出了两种流行的理论,choanoblastaea和synzospore。我们将修正并揭露这两种理论中的缺陷,同时表明,由于我们目前知识的限制,动物的起源是一个生物黑天鹅事件。因此,动物的起源难以追溯。因此,我们应该格外小心,不要陷入基于少数数据的确认偏差,相反,要接受这种不确定性,并对其他情况持开放态度。为了拓宽对动物如何出现的潜在解释,我们在这里提出了两种新颖的替代场景。无论如何,要想找到动物进化的答案,还需要额外的数据,寻找与动物关系密切但尚未采样和研究的微观生物也是如此。
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引用次数: 2
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Annual review of microbiology
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