Current opinion in microbiology最新文献

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Animating insights into the biosynthesis of glycopeptide antibiotics 对糖肽抗生素生物合成的生动见解

IF 5.9 2区生物学 Q1 MICROBIOLOGY

Current opinion in microbiology

Pub Date : 2024-12-01 DOI: 10.1016/j.mib.2024.102561

Athina Gavriilidou , Martina Adamek , Jens-Peter Rodler , Noel Kubach , Anna Voigtländer , Leon Kokkoliadis , Chambers C Hughes , Max J Cryle , Evi Stegmann , Nadine Ziemert

The realm of natural product (NP) research is constantly expanding, with diverse applications in both medicine and industry. In this interdisciplinary field, scientists collaborate to investigate various aspects of NPs, including understanding the mode of action of these compounds, unraveling their biosynthetic pathways, studying evolutionary aspects, and biochemically characterizing the enzymes involved. However, this collaboration can be challenging as all parties involved come from very different backgrounds (such as microbiology, synthetic chemistry, biochemistry, or bioinformatics) and may not use the same terminology. Fortunately, contemporary technologies, such as videos, provide novel avenues for effective engagement. Recognizing the potency of visual stimuli in explaining complex processes, we envision a future where animations become more and more common in interdisciplinary communication, accompanying perspectives, and reviews. To demonstrate how such approaches can enhance the understanding of complex processes, we have animated the biosynthesis of the glycopeptide antibiotic vancomycin (https://youtu.be/TGAgC4c8hvo).

天然产物（NP）研究领域不断扩大，在医学和工业上都有不同的应用。在这个跨学科领域，科学家们合作研究NPs的各个方面，包括了解这些化合物的作用模式，揭示它们的生物合成途径，研究进化方面，以及所涉及的酶的生化特征。然而，这种合作可能具有挑战性，因为所有参与者来自非常不同的背景（如微生物学，合成化学，生物化学或生物信息学），并且可能使用不同的术语。幸运的是，现代技术，如视频，为有效参与提供了新的途径。认识到视觉刺激在解释复杂过程中的潜力，我们设想未来动画在跨学科交流、伴随的观点和评论中变得越来越普遍。为了证明这些方法如何能够增强对复杂过程的理解，我们已经激活了糖肽抗生素万古霉素的生物合成（https://youtu.be/TGAgC4c8hvo）。

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引用次数: 0

Important challenges to finding new leads for new antibiotics 寻找新型抗生素新线索的重要挑战

IF 5.9 2区生物学 Q1 MICROBIOLOGY

Current opinion in microbiology

Pub Date : 2024-11-26 DOI: 10.1016/j.mib.2024.102562

Maya A Farha , Megan M Tu , Eric D Brown

Identification of new antibiotics remains a huge challenge. The last antibiotic of new chemical class and mechanism was discovered more than 30 years ago. Advances since have been largely incremental modifications to a limited number of chemical scaffolds. Discovering and developing truly new antibiotics is challenging: the science is complex, and the development process is time consuming and expensive. Herein, we focus on the discovery phase of modern antibacterial research and development. We argue that antibacterial discovery has been challenged by a poor understanding of bacterial permeability, by generic in vitro conventions that ignore the host, and by the inherent complexity of bacterial systems. Together, these factors have colluded to challenge modern, industrial, and reductionist approaches to antibiotic discovery. Nevertheless, advances in our understanding of many of these obstacles, including a new appreciation for the complexity of both host and pathogen biology, bode well for future efforts.

鉴定新的抗生素仍然是一项巨大的挑战。上一种新化学类别和机制的抗生素是在 30 多年前发现的。此后的进展主要是对数量有限的化学支架进行渐进式修改。发现和开发真正的新型抗生素极具挑战性：科学非常复杂，开发过程耗时且昂贵。在此，我们重点讨论现代抗菌药研发的发现阶段。我们认为，由于对细菌渗透性的不甚了解、忽视宿主的通用体外常规以及细菌系统固有的复杂性，抗菌药的发现一直面临挑战。这些因素共同挑战着现代、工业和还原论的抗生素发现方法。尽管如此，我们对其中许多障碍的理解取得了进展，包括对宿主和病原体生物学复杂性的新认识，这对未来的工作是个好兆头。

引用次数: 0

Temporospatial control of topoisomerases by essential cellular processes 细胞基本过程对拓扑异构酶的时空控制

IF 5.9 2区生物学 Q1 MICROBIOLOGY

Current opinion in microbiology

Pub Date : 2024-11-08 DOI: 10.1016/j.mib.2024.102559

Sora Kim, Monica S Guo

Topoisomerases are essential, ubiquitous enzymes that break and rejoin the DNA strand to control supercoiling. Because topoisomerases are DNA scissors, these enzymes are highly regulated to avoid excessive DNA cleavage, a vulnerability exploited by many antibiotics. Topoisomerase activity must be co-ordinated in time and space with transcription, replication, and cell division or else these processes stall, leading to genome loss. Recent work in Escherichia coli has revealed that topoisomerases do not act alone. Most topoisomerases interact with the essential process that they promote, a coupling that may stimulate topoisomerase activity precisely when and where cleavage is required. Surprisingly, in E. coli and most other bacteria, gyrase is not apparently regulated in this manner. We review how each E. coli topoisomerase is regulated, propose possible solutions to ‘the gyrase problem’, and conclude by highlighting how this regulation may present opportunities for antimicrobial development.

拓扑异构酶是一种重要的、无处不在的酶，可断开和重新连接 DNA 链，从而控制超卷曲。由于拓扑异构酶是 DNA 剪刀，这些酶受到高度调控，以避免过度切割 DNA，而这正是许多抗生素所利用的弱点。拓扑异构酶的活性必须在时间和空间上与转录、复制和细胞分裂相协调，否则这些过程就会停滞，导致基因组丢失。最近在大肠杆菌中进行的研究发现，拓扑异构酶并非单独发挥作用。大多数拓扑异构酶与它们所促进的基本过程相互作用，这种耦合作用可能会在需要裂解的时间和地点精确地刺激拓扑异构酶的活性。令人惊讶的是，在大肠杆菌和大多数其他细菌中，回旋酶显然不是以这种方式调节的。我们回顾了每种大肠杆菌拓扑异构酶是如何被调控的，提出了 "回旋酶问题 "的可能解决方案，最后强调了这种调控如何为抗菌药开发带来机遇。

引用次数: 0

Editorial overview: Human fungal pathogens: An increasing threat 编辑综述：人类真菌病原体：威胁与日俱增。

IF 5.9 2区生物学 Q1 MICROBIOLOGY

Current opinion in microbiology

Pub Date : 2024-10-23 DOI: 10.1016/j.mib.2024.102560

J. Christian Pérez

引用次数: 0

It's complicated: relationships between integrative and conjugative elements and their bacterial hosts 这很复杂：整合元件和共轭元件与其细菌宿主之间的关系

IF 5.9 2区生物学 Q1 MICROBIOLOGY

Current opinion in microbiology

Pub Date : 2024-10-18 DOI: 10.1016/j.mib.2024.102556

Alexa FS Gomberg, Alan D Grossman

Integrative and conjugative elements (ICEs) are typically found integrated in a bacterial host chromosome. They can excise, replicate, and transfer from cell to cell. Many contain genes that confer phenotypes to host cells, including antibiotic resistances, specialized metabolisms, phage defense, and symbiosis or pathogenesis determinants. Recent studies revealed that at least three ICEs (ICEclc, Tn916, and TnSmu1) cause growth arrest or death of host cells upon element activation. This review highlights the complex interactions between ICEs and their hosts, including the recent examples of the significant costs to host cells. We contrast two examples of killing, ICEclc and Tn916, in which killing, respectively, benefits or impairs conjugation and emphasize the importance of understanding the impacts of ICE–host relationships on conjugation. ICEs are typically only active in a small fraction of cells in a population, and we discuss how phenotypes normally occurring in a small subset of host cells can be uncovered.

整合与共轭元件（ICEs）通常整合在细菌宿主染色体中。它们可以切除、复制，并在细胞间转移。其中许多含有赋予宿主细胞表型的基因，包括抗生素抗性、特殊代谢、噬菌体防御以及共生或致病决定因子。最近的研究发现，至少有三种 ICE（ICEclc、Tn916 和 TnSmu1）会在元素激活时导致宿主细胞生长停滞或死亡。这篇综述强调了 ICE 与宿主之间复杂的相互作用，包括宿主细胞付出重大代价的最新实例。我们对比了 ICEclc 和 Tn916 这两个杀灭实例，在这两个实例中，杀灭分别有利于或损害了共轭作用，并强调了了解 ICE-宿主关系对共轭作用影响的重要性。ICE 通常只在群体中的一小部分细胞中活跃，我们将讨论如何揭示通常发生在一小部分宿主细胞中的表型。

引用次数: 0

How do bacteria tune transcription termination efficiency? 细菌如何调节转录终止效率？

IF 5.9 2区生物学 Q1 MICROBIOLOGY

Current opinion in microbiology

Pub Date : 2024-10-17 DOI: 10.1016/j.mib.2024.102557

Kathryn Julia Dierksheide , Robert A. Battaglia , Gene-Wei Li

Bacterial operons often contain intergenic transcription terminators that terminate some, but not all, RNA polymerase molecules. In these operons, the level of terminator readthrough determines downstream gene expression and helps establish protein ratios among co-regulated genes. Despite its critical role in maintaining stoichiometric gene expression, terminator strength remains difficult to predict from DNA sequence. The necessary features of a major class of bacterial terminators — intrinsic terminators — have been known for half a century, but a strong sequence–function model has yet to be developed. Here, we summarize high-throughput approaches for probing the sequence determinants of intrinsic termination efficiency and discuss the impact of trans-acting factors on this sequence–function relationship. Building on the main lessons from these studies, we map out the experimental challenges that must be circumvented to establish a quantitative model for termination efficiency.

细菌操作子通常包含基因间转录终止子，可终止部分而非全部 RNA 聚合酶分子。在这些操作子中，终止子的通读水平决定了下游基因的表达，并有助于确定共调基因之间的蛋白质比例。尽管终止子在维持基因表达的均衡性方面起着关键作用，但终止子的强度仍然难以从 DNA 序列中预测。半个世纪以来，人们已经知道一类主要细菌终止子--固有终止子--的必要特征，但尚未建立一个强大的序列功能模型。在此，我们总结了探测内在终止效率序列决定因素的高通量方法，并讨论了反式作用因子对这种序列-功能关系的影响。基于这些研究的主要经验，我们列出了建立终止效率定量模型所必须克服的实验挑战。

引用次数: 0

Temperature structuring of microbial communities on a global scale 全球微生物群落的温度结构

IF 5.9 2区生物学 Q1 MICROBIOLOGY

Current opinion in microbiology

Pub Date : 2024-10-17 DOI: 10.1016/j.mib.2024.102558

Martina Dal Bello , Clare I Abreu

Temperature is a fundamental physical constraint regulating key aspects of microbial life. Protein binding, membrane fluidity, central dogma processes, and metabolism are all tightly controlled by temperature, such that growth rate profiles across taxa and environments follow the same general curve. An open question in microbial ecology is how the effects of temperature on individual traits scale up to determine community structure and function at planetary scales. Here, we review recent theoretical and experimental efforts to connect physiological responses to the outcome of species interactions, the assembly of microbial communities, and their function as temperature changes. We identify open questions in the field and define a roadmap for future studies.

温度是调节微生物生命关键方面的基本物理约束条件。蛋白质结合、膜流动性、中心教条过程和新陈代谢都受到温度的严格控制，因此不同类群和环境的生长率曲线遵循相同的一般曲线。微生物生态学的一个悬而未决的问题是，温度对个体性状的影响如何扩大到决定行星尺度上的群落结构和功能。在此，我们回顾了最近在理论和实验方面所做的努力，这些努力旨在将生理反应与物种相互作用的结果、微生物群落的组成以及它们在温度变化时的功能联系起来。我们确定了该领域的未决问题，并为未来的研究绘制了路线图。

引用次数: 0

Tapping the treasure trove of atypical phages 挖掘非典型噬菌体的宝库。

IF 5.9 2区生物学 Q1 MICROBIOLOGY

Current opinion in microbiology

Pub Date : 2024-10-10 DOI: 10.1016/j.mib.2024.102555

Simon Roux , Vivek K Mutalik

With advancements in genomics technologies, a vast diversity of ‘atypical’ phages, that is, with single-stranded DNA or RNA genomes, are being uncovered from different ecosystems. Though these efforts have revealed the existence and prevalence of these nonmodel phages, computational approaches often fail to associate these phages with their specific bacterial host(s), while the lack of methods to isolate these phages has limited our ability to characterize infectivity pathways and new gene function. In this review, we call for the development of generalizable experimental methods to better capture this understudied viral diversity via isolation and study them through gene-level characterization and engineering. Establishing a diverse set of new ‘atypical’ phage model systems has the potential to provide many new biotechnologies, including potential uses of these atypical phages in halting the spread of antibiotic resistance and engineering of microbial communities for beneficial outcomes.

随着基因组学技术的进步，人们从不同的生态系统中发现了种类繁多的 "非典型 "噬菌体，即具有单链 DNA 或 RNA 基因组的噬菌体。尽管这些努力揭示了这些非典型噬菌体的存在和普遍性，但计算方法往往无法将这些噬菌体与其特定的细菌宿主联系起来，而缺乏分离这些噬菌体的方法也限制了我们描述感染途径和新基因功能的能力。在这篇综述中，我们呼吁开发可推广的实验方法，通过分离更好地捕捉这种未被充分研究的病毒多样性，并通过基因水平的表征和工程学方法对其进行研究。建立一套多样化的新型 "非典型 "噬菌体模型系统有可能提供许多新的生物技术，包括这些非典型噬菌体在阻止抗生素耐药性传播和微生物群落工程中的潜在用途。

引用次数: 0

Dissecting host–microbe interactions with modern functional genomics 利用现代功能基因组学剖析宿主与微生物之间的相互作用。

IF 5.9 2区生物学 Q1 MICROBIOLOGY

Current opinion in microbiology

Pub Date : 2024-10-04 DOI: 10.1016/j.mib.2024.102554

Baylee J Russell , Manasvi Verma , Nolan K Maier , Marco Jost

Interrogation of host–microbe interactions has long been a source of both basic discoveries and benefits to human health. Here, we review the role that functional genomics approaches have played in such efforts, with an emphasis on recent examples that have harnessed technological advances to provide mechanistic insight at increased scale and resolution. Finally, we discuss how concurrent innovations in model systems and genetic tools have afforded opportunities to interrogate additional types of host–microbe relationships, such as those in the mammalian gut. Bringing these innovations together promises many exciting discoveries ahead.

长期以来，对宿主与微生物相互作用的研究一直是基础发现和人类健康福祉的源泉。在此，我们回顾了功能基因组学方法在这些研究中发挥的作用，并重点介绍了近期利用技术进步在更大范围和更高分辨率上提供机理见解的实例。最后，我们讨论了模型系统和遗传工具的同步创新如何为研究宿主与微生物之间的其他类型关系（如哺乳动物肠道中的关系）提供了机会。将这些创新结合在一起，未来将有许多令人兴奋的发现。

引用次数: 0

Iron–sulfur Rrf2 transcription factors: an emerging versatile platform for sensing stress 铁硫 Rrf2 转录因子：感知压力的新兴多功能平台

IF 5.9 2区生物学 Q1 MICROBIOLOGY

Current opinion in microbiology

Pub Date : 2024-09-24 DOI: 10.1016/j.mib.2024.102543

Rajdeep Banerjee , Isabel Askenasy , Erin L Mettert , Patricia J Kiley

The widespread family of Rrf2 transcription factors has emerged as having prominent roles in diverse bacterial functions. These proteins share an overall common structure to sense and respond to stress signals. In many known cases, signaling occurs through iron–sulfur cluster cofactors. Recent research has highlighted distinct characteristics of individual family members that have enabled the Rrf2 family as a whole to sense a diverse array of stresses and subsequently alter gene expression to maintain homeostasis. Here, we review unique traits of four Rrf2 family members (IscR, NsrR, RisR, and RirA), which include iron–sulfur ligation schemes, stress-sensing mechanisms, protein conformation changes, and differential gene regulation, that allow these transcription factors to rapidly respond to environmental cues routinely encountered by bacteria.

广泛存在的 Rrf2 转录因子家族在细菌的多种功能中发挥着重要作用。这些蛋白质具有共同的整体结构，能够感知和响应压力信号。在许多已知的情况下，信号是通过铁硫簇辅助因子传递的。最近的研究突显了单个家族成员的独特特征，这些特征使 Rrf2 家族作为一个整体能够感知一系列不同的应激，并随之改变基因表达以维持平衡。在此，我们回顾了四个 Rrf2 家族成员（IscR、NsrR、RisR 和 RirA）的独特特征，其中包括铁硫连接方案、压力感应机制、蛋白质构象变化和不同的基因调控，这些特征使这些转录因子能够对细菌经常遇到的环境线索做出快速反应。

引用次数: 0

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