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Molecular Virology of SARS-CoV-2 and Related Coronaviruses. 严重急性呼吸系统综合征冠状病毒2型和相关冠状病毒的分子病毒学。
IF 12.9 1区 生物学 Q1 Medicine Pub Date : 2022-06-15 Epub Date: 2022-03-28 DOI: 10.1128/mmbr.00026-21
Yu-An Kung, Kuo-Ming Lee, Huan-Jung Chiang, Sheng-Yu Huang, Chung-Jung Wu, Shin-Ru Shih

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The global COVID-19 pandemic continues to threaten the lives of hundreds of millions of people, with a severe negative impact on the global economy. Although several COVID-19 vaccines are currently being administered, none of them is 100% effective. Moreover, SARS-CoV-2 variants remain an important worldwide public health issue. Hence, the accelerated development of efficacious antiviral agents is urgently needed. Coronavirus depends on various host cell factors for replication. An ongoing research objective is the identification of host factors that could be exploited as targets for drugs and compounds effective against SARS-CoV-2. In the present review, we discuss the molecular mechanisms of SARS-CoV-2 and related coronaviruses, focusing on the host factors or pathways involved in SARS-CoV-2 replication that have been identified by genome-wide CRISPR screening.

2019冠状病毒病(新冠肺炎)是由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的。全球新冠肺炎疫情继续威胁着数亿人的生命,对全球经济造成严重负面影响。尽管目前正在接种几种新冠肺炎疫苗,但没有一种是100%有效的。此外,严重急性呼吸系统综合征冠状病毒2型变异株仍然是一个重要的全球公共卫生问题。因此,迫切需要加快开发有效的抗病毒药物。冠状病毒依赖于各种宿主细胞因子进行复制。一个正在进行的研究目标是识别宿主因子,这些宿主因子可以作为有效对抗严重急性呼吸系统综合征冠状病毒2型的药物和化合物的靶点。在这篇综述中,我们讨论了严重急性呼吸系统综合征冠状病毒2型和相关冠状病毒的分子机制,重点是通过全基因组CRISPR筛查确定的参与严重急性呼吸系综合征病毒2型复制的宿主因子或途径。
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引用次数: 13
Mechanical Forces Govern Interactions of Host Cells with Intracellular Bacterial Pathogens. 机械力控制宿主细胞与细胞内细菌病原体的相互作用。
IF 12.9 1区 生物学 Q1 Medicine Pub Date : 2022-06-15 DOI: 10.1128/mmbr.00094-20
Effie E Bastounis, Prathima Radhakrishnan, Christopher K Prinz, Julie A Theriot

To combat infectious diseases, it is important to understand how host cells interact with bacterial pathogens. Signals conveyed from pathogen to host, and vice versa, may be either chemical or mechanical. While the molecular and biochemical basis of host-pathogen interactions has been extensively explored, relatively less is known about mechanical signals and responses in the context of those interactions. Nevertheless, a wide variety of bacterial pathogens appear to have developed mechanisms to alter the cellular biomechanics of their hosts in order to promote their survival and dissemination, and in turn many host responses to infection rely on mechanical alterations in host cells and tissues to limit the spread of infection. In this review, we present recent findings on how mechanical forces generated by host cells can promote or obstruct the dissemination of intracellular bacterial pathogens. In addition, we discuss how in vivo extracellular mechanical signals influence interactions between host cells and intracellular bacterial pathogens. Examples of such signals include shear stresses caused by fluid flow over the surface of cells and variable stiffness of the extracellular matrix on which cells are anchored. We highlight bioengineering-inspired tools and techniques that can be used to measure host cell mechanics during infection. These allow for the interrogation of how mechanical signals can modulate infection alongside biochemical signals. We hope that this review will inspire the microbiology community to embrace those tools in future studies so that host cell biomechanics can be more readily explored in the context of infection studies.

为了对抗传染病,了解宿主细胞如何与细菌病原体相互作用是很重要的。从病原体到宿主的信号传递,反之亦然,可能是化学的或机械的。虽然宿主-病原体相互作用的分子和生化基础已被广泛探索,但对这些相互作用背景下的机械信号和反应的了解相对较少。然而,各种各样的细菌病原体似乎已经发展出改变宿主细胞生物力学的机制,以促进它们的生存和传播,反过来,许多宿主对感染的反应依赖于宿主细胞和组织的机械改变来限制感染的传播。在这篇综述中,我们介绍了宿主细胞产生的机械力如何促进或阻碍细胞内细菌病原体的传播的最新发现。此外,我们还讨论了体内细胞外机械信号如何影响宿主细胞和细胞内细菌病原体之间的相互作用。这种信号的例子包括由细胞表面的流体流动引起的剪切应力和细胞锚定的细胞外基质的可变刚度。我们强调生物工程启发的工具和技术,可用于测量宿主细胞力学在感染期间。这使得人们可以探究机械信号如何与生化信号一起调节感染。我们希望这篇综述将激励微生物学界在未来的研究中采用这些工具,以便在感染研究的背景下更容易地探索宿主细胞生物力学。
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引用次数: 6
Advances in the Structural Biology, Mechanism, and Physiology of Cyclopropane Fatty Acid Modifications of Bacterial Membranes. 环丙烷脂肪酸修饰细菌膜的结构生物学、机理和生理学研究进展。
IF 12.9 1区 生物学 Q1 Medicine Pub Date : 2022-06-15 DOI: 10.1128/mmbr.00013-22
John E Cronan, Tiit Luk

Cyclopropane fatty acid (CFA) synthase catalyzes a remarkable reaction. The cis double bonds of unsaturated fatty acyl chains of phospholipid bilayers are converted to cyclopropane rings by transfer of a methylene moiety from S-adenosyl-L-methionine (SAM). The substrates of this modification are functioning membrane bilayer phospholipids. Indeed, in Escherichia coli the great bulk of phospholipid synthesis occurs during exponential growth phase, but most cyclopropyl synthesis occurs in early stationary phase. In vitro the only active methylene group acceptor substrate is phospholipid bilayers containing unsaturated fatty acyl chains.

环丙烷脂肪酸(CFA)合成酶催化了一个显著的反应。磷脂双分子层的不饱和脂肪酸酰基链的顺式双键通过s -腺苷- l-蛋氨酸(SAM)的亚甲基部分转移转化为环丙烷环。这种修饰的底物是功能性膜双层磷脂。事实上,在大肠杆菌中,大部分磷脂合成发生在指数生长期,而大部分环丙基合成发生在固定期的早期。体外唯一活性的亚甲基受体底物是含有不饱和脂肪酸酰基链的磷脂双层。
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引用次数: 5
The ArcAB Two-Component System: Function in Metabolism, Redox Control, and Infection. ArcAB 双组分系统:新陈代谢、氧化还原控制和感染中的功能
IF 8 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2022-06-15 Epub Date: 2022-04-20 DOI: 10.1128/mmbr.00110-21
Aric N Brown, Mark T Anderson, Michael A Bachman, Harry L T Mobley

ArcAB, also known as the Arc system, is a member of the two-component system family of bacterial transcriptional regulators and is composed of sensor kinase ArcB and response regulator ArcA. In this review, we describe the structure and function of these proteins and assess the state of the literature regarding ArcAB as a sensor of oxygen consumption. The bacterial quinone pool is the primary modulator of ArcAB activity, but questions remain for how this regulation occurs. This review highlights the role of quinones and their oxidation state in activating and deactivating ArcB and compares competing models of the regulatory mechanism. The cellular processes linked to ArcAB regulation of central metabolic pathways and potential interactions of the Arc system with other regulatory systems are also reviewed. Recent evidence for the function of ArcAB under aerobic conditions is challenging the long-standing characterization of this system as strictly an anaerobic global regulator, and the support for additional ArcAB functionality in this context is explored. Lastly, ArcAB-controlled cellular processes with relevance to infection are assessed.

ArcAB 又称 Arc 系统,是细菌转录调节器双组分系统家族的成员,由传感器激酶 ArcB 和响应调节器 ArcA 组成。在这篇综述中,我们描述了这些蛋白质的结构和功能,并评估了有关 ArcAB 作为耗氧传感器的文献现状。细菌醌池是 ArcAB 活性的主要调节器,但这种调节是如何发生的仍存在疑问。这篇综述强调了醌及其氧化状态在激活和失活 ArcB 中的作用,并比较了相互竞争的调控机制模型。此外,还综述了与 ArcAB 对中央代谢途径的调控有关的细胞过程,以及 Arc 系统与其他调控系统的潜在相互作用。最近有证据表明 ArcAB 在有氧条件下的功能,这对长期以来将该系统严格定性为厌氧全局调控因子的观点提出了挑战,并探讨了 ArcAB 在这种情况下的其他功能的支持情况。最后,评估了 ArcAB 控制的与感染有关的细胞过程。
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引用次数: 0
An Interplay of Multiple Positive and Negative Factors Governs Methicillin Resistance in Staphylococcus aureus. 多种阳性和阴性因素的相互作用决定了金黄色葡萄球菌对甲氧西林的耐药性。
IF 12.9 1区 生物学 Q1 Medicine Pub Date : 2022-06-15 DOI: 10.1128/mmbr.00159-21
Bohdan L Bilyk, Viralkumar V Panchal, Mariana Tinajero-Trejo, Jamie K Hobbs, Simon J Foster

The development of resistance to β-lactam antibiotics has made Staphylococcus aureus a clinical burden on a global scale. MRSA (methicillin-resistant S. aureus) is commonly known as a superbug. The ability of MRSA to proliferate in the presence of β-lactams is attributed to the acquisition of mecA, which encodes the alternative penicillin binding protein, PBP2A, which is insensitive to the antibiotics. Most MRSA isolates exhibit low-level β-lactam resistance, whereby additional genetic adjustments are required to develop high-level resistance. Although several genetic factors that potentiate or are required for high-level resistance have been identified, how these interact at the mechanistic level has remained elusive. Here, we discuss the development of resistance and assess the role of the associated components in tailoring physiology to accommodate incoming mecA.

对β-内酰胺类抗生素耐药的发展已使金黄色葡萄球菌成为全球范围内的临床负担。MRSA(耐甲氧西林金黄色葡萄球菌)通常被称为超级细菌。MRSA在β-内酰胺存在下的增殖能力归因于mecA的获得,mecA编码替代青霉素结合蛋白PBP2A,该蛋白对抗生素不敏感。大多数MRSA分离株表现出低水平的β-内酰胺耐药性,因此需要额外的基因调整才能产生高水平的耐药性。虽然已经确定了几个增强或需要高水平抗性的遗传因素,但这些因素如何在机制水平上相互作用仍然难以捉摸。在这里,我们讨论了抗性的发展,并评估了相关成分在调整生理以适应传入的mecA中的作用。
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引用次数: 11
Computational Tools for the Analysis of Uncultivated Phage Genomes. 分析未培养噬菌体基因组的计算工具。
IF 8 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2022-06-15 Epub Date: 2022-03-21 DOI: 10.1128/mmbr.00004-21
Juan Sebastián Andrade-Martínez, Laura Carolina Camelo Valera, Luis Alberto Chica Cárdenas, Laura Forero-Junco, Gamaliel López-Leal, J Leonardo Moreno-Gallego, Guillermo Rangel-Pineros, Alejandro Reyes

Over a century of bacteriophage research has uncovered a plethora of fundamental aspects of their biology, ecology, and evolution. Furthermore, the introduction of community-level studies through metagenomics has revealed unprecedented insights on the impact that phages have on a range of ecological and physiological processes. It was not until the introduction of viral metagenomics that we began to grasp the astonishing breadth of genetic diversity encompassed by phage genomes. Novel phage genomes have been reported from a diverse range of biomes at an increasing rate, which has prompted the development of computational tools that support the multilevel characterization of these novel phages based solely on their genome sequences. The impact of these technologies has been so large that, together with MAGs (Metagenomic Assembled Genomes), we now have UViGs (Uncultivated Viral Genomes), which are now officially recognized by the International Committee for the Taxonomy of Viruses (ICTV), and new taxonomic groups can now be created based exclusively on genomic sequence information. Even though the available tools have immensely contributed to our knowledge of phage diversity and ecology, the ongoing surge in software programs makes it challenging to keep up with them and the purpose each one is designed for. Therefore, in this review, we describe a comprehensive set of currently available computational tools designed for the characterization of phage genome sequences, focusing on five specific analyses: (i) assembly and identification of phage and prophage sequences, (ii) phage genome annotation, (iii) phage taxonomic classification, (iv) phage-host interaction analysis, and (v) phage microdiversity.

一个多世纪以来的噬菌体研究揭示了噬菌体生物学、生态学和进化的大量基本方面。此外,通过元基因组学引入的群落级研究也揭示了噬菌体对一系列生态和生理过程所产生的影响,这些都是前所未有的。直到引入病毒元基因组学,我们才开始了解噬菌体基因组所包含的惊人的遗传多样性。新的噬菌体基因组从不同的生物群落中被报道出来的速度越来越快,这促使我们开发了计算工具,仅根据基因组序列就能对这些新的噬菌体进行多层次的特征描述。这些技术的影响如此之大,以至于与 MAGs(元基因组组装基因组)一起,我们现在有了 UViGs(未培养病毒基因组),它现在已被国际病毒分类委员会(ICTV)正式认可,现在可以完全根据基因组序列信息创建新的分类组。尽管现有的工具极大地促进了我们对噬菌体多样性和生态学的了解,但软件程序的不断激增使我们很难跟上它们的步伐,也很难了解每个软件程序的设计目的。因此,在这篇综述中,我们介绍了目前可用的用于描述噬菌体基因组序列特征的一整套计算工具,重点介绍五种具体分析方法:(i) 组装和鉴定噬菌体与噬菌体序列;(ii) 噬菌体基因组注释;(iii) 噬菌体分类;(iv) 噬菌体-宿主相互作用分析;(v) 噬菌体微多样性。
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引用次数: 0
Transcending Dimensions in Apicomplexan Research: from Two-Dimensional to Three-Dimensional In Vitro Cultures. 超越表皮复合菌研究的维度:从二维到三维体外培养。
IF 8 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2022-06-15 Epub Date: 2022-04-12 DOI: 10.1128/mmbr.00025-22
Carlos J Ramírez-Flores, Andrés M Tibabuzo Perdomo, Gina M Gallego-López, Laura J Knoll

Parasites belonging to the Apicomplexa phylum are among the most successful pathogens known in nature. They can infect a wide range of hosts, often remain undetected by the immune system, and cause acute and chronic illness. In this phylum, we can find parasites of human and veterinary health relevance, such as Toxoplasma, Plasmodium, Cryptosporidium, and Eimeria. There are still many unknowns about the biology of these pathogens due to the ethical and practical issues of performing research in their natural hosts. Animal models are often difficult or nonexistent, and as a result, there are apicomplexan life cycle stages that have not been studied. One recent alternative has been the use of three-dimensional (3D) systems such as organoids, 3D scaffolds with different matrices, microfluidic devices, organs-on-a-chip, and other tissue culture models. These 3D systems have facilitated and expanded the research of apicomplexans, allowing us to explore life stages that were previously out of reach and experimental procedures that were practically impossible to perform in animal models. Human- and animal-derived 3D systems can be obtained from different organs, allowing us to model host-pathogen interactions for diagnostic methods and vaccine development, drug testing, exploratory biology, and other applications. In this review, we summarize the most recent advances in the use of 3D systems applied to apicomplexans. We show the wide array of strategies that have been successfully used so far and apply them to explore other organisms that have been less studied.

属于寄生虫门的寄生虫是自然界中已知的最成功的病原体之一。它们可以感染多种宿主,常常不被免疫系统发现,并导致急性和慢性疾病。在这个门中,我们可以找到与人类和兽医健康有关的寄生虫,如弓形虫、疟原虫、隐孢子虫和艾美耳菌。由于在这些病原体的自然宿主体内进行研究存在伦理和实际问题,因此关于这些病原体的生物学特性仍有许多未知数。动物模型往往难以建立或根本不存在,因此,有些类囊体的生命周期阶段尚未得到研究。最近的一种替代方法是使用三维(3D)系统,如有机体、带有不同基质的三维支架、微流体设备、芯片上的器官和其他组织培养模型。这些三维系统促进并扩展了对类囊体的研究,使我们能够探索以前无法触及的生命阶段,以及在动物模型中几乎不可能完成的实验过程。人源和动物源三维系统可从不同器官获得,使我们能够为诊断方法和疫苗开发、药物测试、探索性生物学和其他应用建立宿主-病原体相互作用模型。在这篇综述中,我们总结了将三维系统应用于 apicomplexans 的最新进展。我们展示了迄今为止已成功使用的各种策略,并将其用于探索研究较少的其他生物。
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引用次数: 0
The Facts and Family Secrets of Plasmids That Replicate via the Rolling-Circle Mechanism. 通过滚动循环机制复制的质粒的事实和家族秘密。
IF 12.9 1区 生物学 Q1 Medicine Pub Date : 2022-03-16 DOI: 10.1128/MMBR.00222-20
M Pilar Garcillán-Barcia, Radoslaw Pluta, Fabián Lorenzo-Díaz, Alicia Bravo, Manuel Espinosa

Plasmids are self-replicative DNA elements that are transferred between bacteria. Plasmids encode not only antibiotic resistance genes but also adaptive genes that allow their hosts to colonize new niches. Plasmid transfer is achieved by conjugation (or mobilization), phage-mediated transduction, and natural transformation. Thousands of plasmids use the rolling-circle mechanism for their propagation (RCR plasmids). They are ubiquitous, have a high copy number, exhibit a broad host range, and often can be mobilized among bacterial species. Based upon the replicon, RCR plasmids have been grouped into several families, the best known of them being pC194 and pUB110 (Rep_1 family), pMV158 and pE194 (Rep_2 family), and pT181 and pC221 (Rep_trans family). Genetic traits of RCR plasmids are analyzed concerning (i) replication mediated by a DNA-relaxing initiator protein and its interactions with the cognate DNA origin, (ii) lagging-strand origins of replication, (iii) antibiotic resistance genes, (iv) mobilization functions, (v) replication control, performed by proteins and/or antisense RNAs, and (vi) the participating host-encoded functions. The mobilization functions include a relaxase initiator of transfer (Mob), an origin of transfer, and one or two small auxiliary proteins. There is a family of relaxases, the MOBV family represented by plasmid pMV158, which has been revisited and updated. Family secrets, like a putative open reading frame of unknown function, are reported. We conclude that basic research on RCR plasmids is of importance, and our perspectives contemplate the concept of One Earth because we should incorporate bacteria into our daily life by diminishing their virulence and, at the same time, respecting their genetic diversity.

质粒是在细菌之间转移的自我复制的DNA元素。质粒不仅编码抗生素抗性基因,还编码适应性基因,使宿主能够在新的生态位定居。质粒转移是通过偶联(或动员)、噬菌体介导的转导和自然转化来实现的。成千上万的质粒使用滚动循环机制进行繁殖(RCR质粒)。它们无处不在,具有高拷贝数,表现出广泛的宿主范围,并且经常可以在细菌物种之间调动。根据复制子的不同,RCR质粒被分为几个家族,其中最著名的是pC194和pUB110 (Rep_1家族),pMV158和pE194 (Rep_2家族),pT181和pC221 (Rep_trans家族)。分析了RCR质粒的遗传性状,包括:(i) DNA放松启动蛋白介导的复制及其与同源DNA起源的相互作用,(ii)复制的滞后链起源,(iii)抗生素抗性基因,(iv)动员功能,(v)由蛋白质和/或反义rna执行的复制控制,以及(vi)参与宿主编码的功能。动员功能包括转移的松弛引发剂(Mob),转移的起源,和一个或两个小的辅助蛋白。有一个松弛家族,以质粒pMV158为代表的MOBV家族,已经被重新审视和更新。家庭秘密,如未知功能的假定开放阅读框架,被报道。我们的结论是,对RCR质粒的基础研究是重要的,我们的观点是考虑一个地球的概念,因为我们应该通过减少细菌的毒性,同时尊重它们的遗传多样性,将细菌纳入我们的日常生活。
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引用次数: 6
Evolutionary Morphogenesis of Sexual Fruiting Bodies in Basidiomycota: Toward a New Evo-Devo Synthesis. 担子菌性子实体的进化形态发生:一种新的进化- devo合成。
IF 12.9 1区 生物学 Q1 Medicine Pub Date : 2022-03-16 Epub Date: 2021-11-24 DOI: 10.1128/MMBR.00019-21
Máté Virágh, Zsolt Merényi, Árpád Csernetics, Csenge Földi, Neha Sahu, Xiao-Bin Liu, David S Hibbett, László G Nagy

The development of sexual fruiting bodies is one of the most complex morphogenetic processes in fungi. Mycologists have long been fascinated by the morphological and developmental diversity of fruiting bodies; however, evolutionary developmental biology of fungi still lags significantly behind that of animals or plants. Here, we summarize the current state of knowledge on fruiting bodies of mushroom-forming Basidiomycota, focusing on phylogenetic and developmental biology. Phylogenetic approaches have revealed a complex history of morphological transformations and convergence in fruiting body morphologies. Frequent transformations and convergence is characteristic of fruiting bodies in contrast to animals or plants, where main body plans are highly conserved. At the same time, insights into the genetic bases of fruiting body development have been achieved using forward and reverse genetic approaches in selected model systems. Phylogenetic and developmental studies of fruiting bodies have each yielded major advances, but they have produced largely disjunct bodies of knowledge. An integrative approach, combining phylogenetic, developmental, and functional biology, is needed to achieve a true fungal evolutionary developmental biology (evo-devo) synthesis for fungal fruiting bodies.

性子实体的发育是真菌最复杂的形态发生过程之一。真菌学家长期以来一直对子实体的形态和发育多样性着迷;然而,真菌的进化发育生物学仍然明显落后于动物或植物。本文从系统发育生物学和发育生物学两方面综述了目前有关成菇担子菌属子实体的研究现状。系统发育方法揭示了子实体形态变化和收敛的复杂历史。频繁的转换和收敛是子实体的特点,而动物或植物的主体计划是高度保守的。同时,对子实体发育的遗传基础的见解已经在选定的模型系统中使用正向和反向遗传方法实现。子实体的系统发育和发育研究都取得了重大进展,但它们产生的知识体系在很大程度上是脱节的。需要一种综合的方法,结合系统发育,发育和功能生物学,来实现真菌子实体的真正进化发育生物学(evo-devo)合成。
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引用次数: 7
Chemotropism and Cell-Cell Fusion in Fungi. 真菌的趋化性和细胞-细胞融合。
IF 12.9 1区 生物学 Q1 Medicine Pub Date : 2022-03-16 DOI: 10.1128/mmbr.00165-21
Manuella R Clark-Cotton, Katherine C Jacobs, Daniel J Lew

Fungi exhibit an enormous variety of morphologies, including yeast colonies, hyphal mycelia, and elaborate fruiting bodies. This diversity arises through a combination of polar growth, cell division, and cell fusion. Because fungal cells are nonmotile and surrounded by a protective cell wall that is essential for cell integrity, potential fusion partners must grow toward each other until they touch and then degrade the intervening cell walls without impacting cell integrity. Here, we review recent progress on understanding how fungi overcome these challenges. Extracellular chemoattractants, including small peptide pheromones, mediate communication between potential fusion partners, promoting the local activation of core cell polarity regulators to orient polar growth and cell wall degradation. However, in crowded environments, pheromone gradients can be complex and potentially confusing, raising the question of how cells can effectively find their partners. Recent findings suggest that the cell polarity circuit exhibits searching behavior that can respond to pheromone cues through a remarkably flexible and effective strategy called exploratory polarization.

真菌表现出多种多样的形态,包括酵母菌落、菌丝和精致的子实体。这种多样性是通过极性生长、细胞分裂和细胞融合的结合而产生的。由于真菌细胞是不运动的,并且被保护细胞壁所包围,这对细胞的完整性至关重要,因此潜在的融合伙伴必须彼此生长,直到它们接触并降解中间的细胞壁,而不影响细胞的完整性。在这里,我们回顾了真菌如何克服这些挑战的最新进展。细胞外化学引诱剂,包括小肽信息素,介导潜在融合伙伴之间的通信,促进核心细胞极性调节因子的局部激活,以定向极性生长和细胞壁降解。然而,在拥挤的环境中,信息素的梯度可能是复杂的,并且可能令人困惑,这就提出了细胞如何有效地找到它们的伴侣的问题。最近的研究表明,细胞极性电路表现出搜索行为,可以通过一种非常灵活和有效的策略来响应信息素的提示,这种策略被称为探索性极化。
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引用次数: 6
期刊
Microbiology and Molecular Biology Reviews
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