Pub Date : 2025-02-01Epub Date: 2025-01-21DOI: 10.1016/j.mib.2025.102579
Zihua Liu , Chu Wang
The molecular essence of the battle between host and pathogens lies in the protein–protein or protein–metabolite interactions. Itaconate is one of the most upregulated immunometabolites, regulating immune responses through either noncovalent binding or covalent modification in the host. We herein briefly review recent progresses in the discoveries of physiological and pathological roles of itaconate and applications of chemical proteomic technologies in exploring itaconate modifications on cysteines (S-itaconation) at the interface of host–pathogen interactions. Key challenges are also proposed as future outlook.
{"title":"Dissecting S-itaconation at host–pathogen interactions with chemical proteomics tools","authors":"Zihua Liu , Chu Wang","doi":"10.1016/j.mib.2025.102579","DOIUrl":"10.1016/j.mib.2025.102579","url":null,"abstract":"<div><div>The molecular essence of the battle between host and pathogens lies in the protein–protein or protein–metabolite interactions. Itaconate is one of the most upregulated immunometabolites, regulating immune responses through either noncovalent binding or covalent modification in the host. We herein briefly review recent progresses in the discoveries of physiological and pathological roles of itaconate and applications of chemical proteomic technologies in exploring itaconate modifications on cysteines (<em>S</em>-itaconation) at the interface of host–pathogen interactions. Key challenges are also proposed as future outlook.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"83 ","pages":"Article 102579"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01Epub Date: 2024-11-26DOI: 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.
{"title":"Important challenges to finding new leads for new antibiotics","authors":"Maya A Farha , Megan M Tu , Eric D Brown","doi":"10.1016/j.mib.2024.102562","DOIUrl":"10.1016/j.mib.2024.102562","url":null,"abstract":"<div><div>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 <em>in vitro</em> 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.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"83 ","pages":"Article 102562"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-09-05DOI: 10.1016/j.mib.2024.102537
Georgia R Squyres , Dianne K Newman
Although our understanding of both bacterial cell physiology and the complex behaviors exhibited by bacterial biofilms is expanding rapidly, we cannot yet sum the behaviors of individual cells to understand or predict biofilm behavior. This is both because cell physiology in biofilms is different from planktonic growth and because cell behavior in biofilms is spatiotemporally patterned. We use developmental biology as a guide to examine this phenotypic patterning, discussing candidate cues that may encode spatiotemporal information and possible roles for phenotypic patterning in biofilms. We consider other questions that arise from the comparison between biofilm and eukaryotic development, including what defines normal biofilm development and the nature of biofilm cell types and fates. We conclude by discussing what biofilm development can tell us about developmental processes, emphasizing the additional challenges faced by bacteria in biofilm development compared with their eukaryotic counterparts.
{"title":"Biofilms as more than the sum of their parts: lessons from developmental biology","authors":"Georgia R Squyres , Dianne K Newman","doi":"10.1016/j.mib.2024.102537","DOIUrl":"10.1016/j.mib.2024.102537","url":null,"abstract":"<div><p>Although our understanding of both bacterial cell physiology and the complex behaviors exhibited by bacterial biofilms is expanding rapidly, we cannot yet sum the behaviors of individual cells to understand or predict biofilm behavior. This is both because cell physiology in biofilms is different from planktonic growth and because cell behavior in biofilms is spatiotemporally patterned. We use developmental biology as a guide to examine this phenotypic patterning, discussing candidate cues that may encode spatiotemporal information and possible roles for phenotypic patterning in biofilms. We consider other questions that arise from the comparison between biofilm and eukaryotic development, including what defines normal biofilm development and the nature of biofilm cell types and fates. We conclude by discussing what biofilm development can tell us about developmental processes, emphasizing the additional challenges faced by bacteria in biofilm development compared with their eukaryotic counterparts.</p></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"82 ","pages":"Article 102537"},"PeriodicalIF":5.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-11-29DOI: 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).
{"title":"Animating insights into the biosynthesis of glycopeptide antibiotics","authors":"Athina Gavriilidou , Martina Adamek , Jens-Peter Rodler , Noel Kubach , Anna Voigtländer , Leon Kokkoliadis , Chambers C Hughes , Max J Cryle , Evi Stegmann , Nadine Ziemert","doi":"10.1016/j.mib.2024.102561","DOIUrl":"10.1016/j.mib.2024.102561","url":null,"abstract":"<div><div>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).</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"82 ","pages":"Article 102561"},"PeriodicalIF":5.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-09-18DOI: 10.1016/j.mib.2024.102542
Fernanda Pinheiro
Predicting the evolution of antibiotic resistance is critical for realizing precision antibiotic therapies. How exactly to achieve such predictions is a theoretical challenge. Insights from mathematical models that reflect future behavior of microbes under antibiotic stress can inform intervention protocols. However, this requires going beyond heuristic approaches by modeling ecological and evolutionary responses linked to metabolic pathways and cellular functions. Developing such models is now becoming possible due to increasing data availability from systematic experiments with microbial systems. Here, I review recent theoretical advances promising building blocks to piece together a predictive theory of antibiotic resistance evolution. I focus on the conceptual framework of eco-evolutionary response models grounded on quantitative laws of bacterial physiology. These forward-looking models can predict previously unknown behavior of bacteria upon antibiotic exposure. With current developments covering mostly the case of ribosome-targeting antibiotics, I write this Opinion piece as an invitation to generalize the principles discussed here to a broader range of drugs and context dependencies.
{"title":"Predicting the evolution of antibiotic resistance","authors":"Fernanda Pinheiro","doi":"10.1016/j.mib.2024.102542","DOIUrl":"10.1016/j.mib.2024.102542","url":null,"abstract":"<div><p>Predicting the evolution of antibiotic resistance is critical for realizing precision antibiotic therapies. How exactly to achieve such predictions is a theoretical challenge. Insights from mathematical models that reflect future behavior of microbes under antibiotic stress can inform intervention protocols. However, this requires going beyond heuristic approaches by modeling ecological and evolutionary responses linked to metabolic pathways and cellular functions. Developing such models is now becoming possible due to increasing data availability from systematic experiments with microbial systems. Here, I review recent theoretical advances promising building blocks to piece together a predictive theory of antibiotic resistance evolution. I focus on the conceptual framework of eco-evolutionary response models grounded on quantitative laws of bacterial physiology. These forward-looking models can predict previously unknown behavior of bacteria upon antibiotic exposure. With current developments covering mostly the case of ribosome-targeting antibiotics, I write this Opinion piece as an invitation to generalize the principles discussed here to a broader range of drugs and context dependencies.</p></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"82 ","pages":"Article 102542"},"PeriodicalIF":5.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1369527424001188/pdfft?md5=c5a40650bac522618648ffd0caa862ca&pid=1-s2.0-S1369527424001188-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-10-10DOI: 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。
{"title":"Tapping the treasure trove of atypical phages","authors":"Simon Roux , Vivek K Mutalik","doi":"10.1016/j.mib.2024.102555","DOIUrl":"10.1016/j.mib.2024.102555","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"82 ","pages":"Article 102555"},"PeriodicalIF":5.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-11-08DOI: 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。
{"title":"Temporospatial control of topoisomerases by essential cellular processes","authors":"Sora Kim, Monica S Guo","doi":"10.1016/j.mib.2024.102559","DOIUrl":"10.1016/j.mib.2024.102559","url":null,"abstract":"<div><div>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 <em>Escherichia coli</em> 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 <em>E. coli</em> and most other bacteria, gyrase is not apparently regulated in this manner. We review how each <em>E. coli</em> topoisomerase is regulated, propose possible solutions to ‘the gyrase problem’, and conclude by highlighting how this regulation may present opportunities for antimicrobial development.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"82 ","pages":"Article 102559"},"PeriodicalIF":5.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-09-10DOI: 10.1016/j.mib.2024.102539
Jessica CS Brown , Elizabeth R Ballou
Improved understanding of the human fungal pathogen Cryptococcus neoformans, classically described as a basidiomycete budding yeast, has revealed new infection-relevant single cell morphologies in vivo and in vitro. Here, we ask whether these morphologies constitute true morphotypes, requiring updated classification of C. neoformans as a pleomorphic fungus. We profile recent discoveries of C. neoformans seed cells and titan cells and provide a framework for determining whether these and other recently described single-cell morphologies constitute true morphotypes. We demonstrate that multiple C. neoformans single-cell morphologies are transcriptionally distinct, stable, heritable, and associated with active growth and therefore should be considered true morphotypes in line with the classification in other well-studied fungi. We conclude that C. neoformans is a pleomorphic fungus with an important capacity for morphotype switching that underpins pathogenesis.
人们对人类真菌病原体新隐球菌（Cryptococcus neoformans）的了解有所加深，这种真菌通常被描述为一种基生真菌发芽酵母，而我们对其体内和体外新的感染相关单细胞形态的了解也有所加深。在这里，我们要问的是，这些形态是否构成了真正的形态型，是否需要将新球菌更新分类为多形真菌。我们介绍了最近发现的 C. neoformans 种子细胞和泰坦细胞，并提供了一个框架来确定这些和其他最近描述的单细胞形态是否构成真正的形态型。我们证明，C. neoformans 的多种单细胞形态在转录上是不同的、稳定的、可遗传的，并且与活跃的生长有关，因此应被视为真正的形态型，这与其他研究充分的真菌的分类方法一致。我们的结论是，新变形菌是一种多形真菌，具有重要的形态切换能力，是致病机理的基础。
{"title":"Is Cryptococcus neoformans a pleomorphic fungus?","authors":"Jessica CS Brown , Elizabeth R Ballou","doi":"10.1016/j.mib.2024.102539","DOIUrl":"10.1016/j.mib.2024.102539","url":null,"abstract":"<div><p>Improved understanding of the human fungal pathogen <em>Cryptococcus neoformans,</em> classically described as a basidiomycete budding yeast, has revealed new infection-relevant single cell morphologies <em>in vivo</em> and <em>in vitro</em>. Here, we ask whether these morphologies constitute true morphotypes, requiring updated classification of <em>C. neoformans</em> as a pleomorphic fungus. We profile recent discoveries of <em>C. neoformans</em> seed cells and titan cells and provide a framework for determining whether these and other recently described single-cell morphologies constitute true morphotypes. We demonstrate that multiple <em>C. neoformans</em> single-cell morphologies are transcriptionally distinct, stable, heritable, and associated with active growth and therefore should be considered true morphotypes in line with the classification in other well-studied fungi. We conclude that <em>C. neoformans</em> is a pleomorphic fungus with an important capacity for morphotype switching that underpins pathogenesis.</p></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"82 ","pages":"Article 102539"},"PeriodicalIF":5.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1369527424001152/pdfft?md5=81c0fd0affe38894e43d774b7273774c&pid=1-s2.0-S1369527424001152-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142163311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-10-17DOI: 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。
{"title":"How do bacteria tune transcription termination efficiency?","authors":"Kathryn Julia Dierksheide , Robert A. Battaglia , Gene-Wei Li","doi":"10.1016/j.mib.2024.102557","DOIUrl":"10.1016/j.mib.2024.102557","url":null,"abstract":"<div><div>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 <em>trans</em>-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.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"82 ","pages":"Article 102557"},"PeriodicalIF":5.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Iron–sulfur Rrf2 transcription factors: an emerging versatile platform for sensing stress","authors":"Rajdeep Banerjee , Isabel Askenasy , Erin L Mettert , Patricia J Kiley","doi":"10.1016/j.mib.2024.102543","DOIUrl":"10.1016/j.mib.2024.102543","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"82 ","pages":"Article 102543"},"PeriodicalIF":5.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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