Cell Surface最新文献

英文中文

Endocytic tethers modulate unconventional GAPDH secretion 内吞系索调节非常规GAPDH分泌。

Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2024-12-24 DOI: 10.1016/j.tcsw.2024.100138

Michael J. Cohen , Brianne Philippe , Peter N. Lipke

Yeast cell walls contain both classically-secreted and unconventionally-secreted proteins. The latter class lacks the signal sequence for translocation into the ER, therefore these proteins are transported to the wall by uncharacterized mechanisms. One such protein is the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which is abundant in the cytosol, but also found in the yeast cell wall where it is enzymatically active. We screened diploid Saccharomyces cerevisiae homozygous gene deletions for changes in cell wall GAPDH activity. Deletions targeting endocytic tethers in the endolysosomal system had the largest effects on GAPDH secretion, including vps21, bro1, vps41, and pep12. The predominant GAPDH isoform Tdh3 was partially localized to endolysosomal compartments, including multivesicular bodies, which are common entry points to unconventional protein secretion pathways. Yeast lacking the endosomal Rab5-GTPase Vps21 had defects in GAPDH secretion as well as delayed entry into to the endolysosomal compartments. Therefore, we conclude that entry into the endolysosomal compartment facilitates non-conventional secretion of GAPDH.

酵母细胞壁包含经典分泌和非常规分泌的蛋白质。后一类缺乏转运到内质网的信号序列，因此这些蛋白质通过未知的机制转运到壁。其中一种蛋白质是糖酵解酶甘油醛-3-磷酸脱氢酶（GAPDH），它丰富于细胞质中，但也存在于酵母菌细胞壁中，在那里它具有酶活性。我们筛选二倍体酿酒酵母纯合基因缺失的细胞壁GAPDH活性的变化。内溶酶体系统中针对内噬系链的缺失对GAPDH分泌的影响最大，包括vps21、bro1、vps41和pep12。主要的GAPDH亚型Tdh3部分定位于内溶酶体室室，包括多泡体，这是非常规蛋白质分泌途径的常见入口点。缺乏内体Rab5-GTPase Vps21的酵母在GAPDH分泌方面存在缺陷，并且延迟进入内溶酶体腔室。因此，我们得出结论，进入内溶酶体室有助于GAPDH的非常规分泌。

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引用次数: 0

Mucilicious methods: Navigating the tools developed to Arabidopsis Seed Coat Mucilage analysis 黏液分析方法：导航拟南芥种皮黏液分析工具。

Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2024-12-11 DOI: 10.1016/j.tcsw.2024.100134

Susana Saez-Aguayo , Dayan Sanhueza , Vicente Jara , Benjamin Galleguillos , Alfonso Gonzalo de la Rubia , Asier Largo-Gosens , Adrian Moreno

During the last decades, Arabidopsis seed mucilage has been extensively studied to gain insight into the metabolism of pectin, hemicellulose and cellulose. This review aims to provide a comprehensive examination of the techniques used to understand the composition and structure of Arabidopsis mucilage. Moreover, we present novel findings from mucilage analysis, including the separation of pectic domains within the mucilage, offering a fresh perspective on utilizing traditional techniques to analyze mucilage mutant lines.

在过去的几十年里，人们对拟南芥种子粘液进行了广泛的研究，以深入了解果胶、半纤维素和纤维素的代谢。本文综述了拟南芥粘液组成和结构的研究进展。此外，我们还介绍了粘液分析的新发现，包括粘液中果胶结构域的分离，为利用传统技术分析粘液突变系提供了新的视角。

引用次数: 0

Staphylococcus aureus: Current perspectives on molecular pathogenesis and virulence 金黄色葡萄球菌：分子发病机制和毒力的最新研究进展。

Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2024-12-09 DOI: 10.1016/j.tcsw.2024.100137

Abayeneh Girma

Staphylococcus aureus has evolved a sophisticated regulatory system to control its virulence. One of the main roles of this interconnected network is to sense and respond to diverse environmental signals by altering the synthesis of virulence components required for survival in the host, including cell surface adhesins, extracellular enzymes and toxins. The accessory gene regulator (agr), a quorum sensing system that detects the local concentration of a cyclic peptide signaling molecule, is one of the well-studied of these S. aureus regulatory mechanisms. By using this system, S. aureus is able to sense its own population density and translate this information into a specific pattern of gene expression. In addition to Agr, this pathogen senses specific stimuli through various two-component systems and synchronizes responses with alternative sigma factors and cytoplasmic regulators of the SarA protein family. These different regulatory mechanisms combine host and environmental information into a network that guarantees the best possible response of pathogens to changing circumstances. In this article, an overview of the most significant and thoroughly studied regulatory systems of S. aureus is provided, along with a summary of their roles in host interactions.

金黄色葡萄球菌已经进化出一个复杂的调控系统来控制它的毒力。这个相互连接的网络的主要作用之一是通过改变宿主生存所需的毒力成分的合成，包括细胞表面粘附素、细胞外酶和毒素，来感知和响应各种环境信号。辅助基因调控（agr）是一种群体感应系统，可检测环肽信号分子的局部浓度，是这些金黄色葡萄球菌调控机制中研究得很好的一个。通过使用这个系统，金黄色葡萄球菌能够感知自身的种群密度，并将这些信息转化为特定的基因表达模式。除了Agr，这种病原体通过各种双组分系统感知特定刺激，并与其他sigma因子和SarA蛋白家族的细胞质调节因子同步反应。这些不同的调节机制将宿主和环境信息结合成一个网络，保证病原体对不断变化的环境做出最佳反应。本文概述了金黄色葡萄球菌最重要和最深入研究的调控系统，并总结了它们在宿主相互作用中的作用。

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引用次数: 0

Spatiotemporal regulation of alginate sub-structures at multiple scales revealed by monoclonal antibodies 单克隆抗体揭示海藻酸盐亚结构在多尺度上的时空调控。

Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2024-12-08 DOI: 10.1016/j.tcsw.2024.100136

Catherine T. Jones , Cassie Bakshani , Ieva Lelenaite , Jozef Mravec , Stjepan Krešimir Kračun , Jeff Pearson , Mathew D. Wilcox , Kevin Hardouin , Sonia Kridi , Cécile Hervé , William G.T. Willats

Alginates are abundant linear polysaccharides produced by brown algae and some bacteria. They have multiple biological roles and important medical and commercial uses. Alginates are comprised of D-mannuronic acid (M) and L-guluronic acid (G) and the ratios and distribution patterns of M and G profoundly impact their physiological and rheological properties. The structure/function relationships of alginates have been extensively studied in vitro but our understanding of the in vivo spatiotemporal regulation of alginate fine structures and their biological implications is limited. Monoclonal antibodies (mAbs) are powerful tools for localising and quantifying glycan structures and several alginate-directed mAbs have been developed. We used a library of well-defined alginates, with M and G block ratios determined by NMR, to refine our understanding of the binding properties of alginate-directed mAbs. Using these probes, we obtained new insight into how structural features of alginates are regulated at different scales, from cellular to seasonal.

褐藻酸盐是由褐藻和一些细菌产生的丰富的线状多糖。它们具有多种生物学作用和重要的医学和商业用途。海藻酸盐由d -甘露醛酸(M)和l -古鲁醛酸(G)组成，M和G的比例和分布规律对其生理和流变特性有重要影响。藻酸盐的结构/功能关系已经在体外得到了广泛的研究，但我们对藻酸盐精细结构的体内时空调节及其生物学意义的了解有限。单克隆抗体（mab）是定位和定量多糖结构的有力工具，目前已开发出几种海藻酸盐定向单克隆抗体。我们使用了一个定义明确的海藻酸盐库，通过核磁共振确定M和G块比，来完善我们对海藻酸盐定向单克隆抗体结合特性的理解。利用这些探针，我们对海藻酸盐的结构特征如何在不同的尺度上受到调节有了新的认识，从细胞到季节。

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引用次数: 0

Advances on cell wall biology: Highlights from the XVI Plant Cell Wall Meeting 细胞壁生物学研究进展：第十六届植物细胞壁会议要点

Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2024-12-01 DOI: 10.1016/j.tcsw.2024.100130

Hugo Mélida , Antonio Molina

引用次数: 0

Antimicrobial peptides and proteins against drug-resistant pathogens 抗耐药性病原体的抗菌肽和蛋白质

Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2024-12-01 DOI: 10.1016/j.tcsw.2024.100135

Yeji Wang, Minghui Song, Wenqiang Chang

The rise of drug-resistant pathogens, driven by the misuse and overuse of antibiotics, has created a formidable challenge for global public health. Antimicrobial peptides and proteins have garnered considerable attention as promising candidates for novel antimicrobial agents. These bioactive molecules, whether derived from natural sources, designed synthetically, or predicted using artificial intelligence, can induce lethal effects on pathogens by targeting key microbial structures or functional components, such as cell membranes, cell walls, biofilms, and intracellular components. Additionally, they may enhance overall immune defenses by modulating innate or adaptive immune responses in the host. Of course, development of antimicrobial peptides and proteins also face some limitations, including high toxicity, lack of selectivity, insufficient stability, and potential immunogenicity. Despite these challenges, they remain a valuable resource in the fight against drug-resistant pathogens. Future research should focus on overcoming these limitations to fully realize the therapeutic potential of antimicrobial peptides in the infection control.

抗生素的滥用和过度使用导致耐药病原体的增加，给全球公共卫生带来了巨大挑战。抗菌肽和蛋白质作为新型抗菌药物的有前途的候选者已经引起了相当大的关注。这些生物活性分子，无论是来自天然来源、合成设计还是使用人工智能预测，都可以通过靶向关键微生物结构或功能成分（如细胞膜、细胞壁、生物膜和细胞内成分）对病原体产生致命影响。此外，它们可能通过调节宿主的先天或适应性免疫反应来增强整体免疫防御。当然，抗菌肽和抗菌蛋白的发展也面临着一些限制，包括高毒性、缺乏选择性、稳定性不足和潜在的免疫原性。尽管存在这些挑战，它们仍然是抗击耐药病原体的宝贵资源。今后的研究应着眼于克服这些局限性，以充分发挥抗菌肽在感染控制中的治疗潜力。

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引用次数: 0

Combatting biofilm-mediated infections in clinical settings by targeting quorum sensing 以法定人数感应为目标，抗击临床环境中生物膜介导的感染

Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2024-11-08 DOI: 10.1016/j.tcsw.2024.100133

Arindam Mitra

Biofilm-associated infections constitute a significant challenge in managing infectious diseases due to their high resistance to antibiotics and host immune responses. Biofilms are responsible for various infections, including urinary tract infections, cystic fibrosis, dental plaque, bone infections, and chronic wounds. Quorum sensing (QS) is a process of cell-to-cell communication that bacteria use to coordinate gene expression in response to cell density, which is crucial for biofilm formation and maintenance.. Its disruption has been proposed as a potential strategy to prevent or treat biofilm-associated infections leading to improved treatment outcomes for infectious diseases. This review article aims to provide a comprehensive overview of the literature on QS-mediated disruption of biofilms for treating infectious diseases. It will discuss the mechanisms of QS disruption and the various approaches that have been developed to disrupt QS in reference to multiple clinical pathogens. In particular, numerous studies have demonstrated the efficacy of QS disruption in reducing biofilm formation in various pathogens, including Pseudomonas aeruginosa and Staphylococcus aureus. Finally, the review will discuss the challenges and future directions for developing QS disruption as a clinical therapy for biofilm-associated infections. This includes the development of effective delivery systems and the identification of suitable targets for QS disruption. Overall, the literature suggests that QS disruption is a promising alternative to traditional antibiotic treatment for biofilm-associated infections and warrants further investigation.

由于生物膜对抗生素和宿主免疫反应具有很强的抗药性，因此与生物膜相关的感染是控制传染病的一大挑战。生物膜是各种感染的罪魁祸首，包括尿路感染、囊性纤维化、牙菌斑、骨感染和慢性伤口。法定量感应（QS）是细菌根据细胞密度协调基因表达的细胞间通信过程，对生物膜的形成和维持至关重要。人们已提出将破坏这一过程作为预防或治疗生物膜相关感染的潜在策略，从而改善传染性疾病的治疗效果。这篇综述文章旨在全面概述有关 QS 介导的破坏生物膜以治疗传染性疾病的文献。文章将讨论 QS 破坏的机制以及针对多种临床病原体开发的各种破坏 QS 的方法。特别是，许多研究已经证明了 QS 破坏在减少包括铜绿假单胞菌和金黄色葡萄球菌在内的各种病原体的生物膜形成方面的功效。最后，本综述将讨论开发 QS 破坏作为生物膜相关感染临床疗法所面临的挑战和未来发展方向。这包括开发有效的给药系统和确定合适的 QS 破坏靶点。总之，文献表明 QS 干扰是治疗生物膜相关感染的传统抗生素疗法的一种有前途的替代疗法，值得进一步研究。

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引用次数: 0

The role of ABC transporter DrrABC in the export of PDIM in Mycobacterium tuberculosis ABC 转运体 DrrABC 在结核分枝杆菌 PDIM 的输出过程中的作用

Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2024-10-15 DOI: 10.1016/j.tcsw.2024.100132

Nabiela Moolla , Helen Weaver , Rebeca Bailo , Albel Singh , Vassiliy N. Bavro , Apoorva Bhatt

The Mycobacterium tuberculosis virulence lipid phthiocerol dimycocerosate (PDIM) is exported by a complex mechanism that involves multiple proteins including the Resistance-Nodulation-Division (RND) transporter MmpL7 and the lipoprotein LppX. Here, we probe the role of the putative heterooligomeric ATP-Binding Cassette (ABC) transporter complex composed of DrrA, DrrB and DrrC in PDIM transport by constructing a set of individual null mutants of drrA, drrB and drrC in the vaccine strain Mycobacterium bovis BCG. Loss of all three, or individual drr genes, all resulted in a complete loss of PDIM export to the outer envelope of the mycobacterial cell. Furthermore, guided by a bioinformatic analysis we interrogated specific signature residues within the DrrABC to demonstrate that it is indeed an ABC transporter, and our modelling, together with the mutagenesis identify it as a member of the Type V family of ABC exporters. We identify several unique structural elements of the transporter, including a non-canonical C-terminally inserted domain (CTD) structure within DrrA, which may account for its functional properties.

结核分枝杆菌毒力脂质酞酰芹醇二甲芹糖酯（PDIM）的输出机制复杂，涉及多种蛋白质，包括抗性-结节-分裂（RND）转运体 MmpL7 和脂蛋白 LppX。在这里，我们通过在疫苗菌株卡介苗中构建一组 drrA、drrB 和 drrC 的单个无效突变体，探究了由 DrrA、DrrB 和 DrrC 组成的假定异源同源 ATP 结合盒（ABC）转运体复合物在 PDIM 转运中的作用。所有三个或单个 drr 基因的缺失都会导致 PDIM 完全丧失向分枝杆菌细胞外包膜的输出。此外，在生物信息学分析的指导下，我们询问了 DrrrABC 中的特定特征残基，证明它确实是 ABC 转运体，我们的建模和诱变确定它是 ABC 转运体 V 型家族的成员。我们确定了该转运体的几个独特结构元素，包括 DrrA 中的非经典 C 端插入结构域 (CTD)，这可能是其功能特性的原因。

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引用次数: 0

Sorting of GPI-anchored proteins at the trypanosome surface is independent of GPI insertion signals 锥虫表面 GPI-anchored 蛋白质的分拣与 GPI 插入信号无关

Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2024-07-06 DOI: 10.1016/j.tcsw.2024.100131

Thomas Henry Miller, Sabine Schiessler, Ella Maria Rogerson, Catarina Gadelha

The segregation of glycosylphosphatidylinositol-anchored proteins (GPI-APs) to distinct domains on the plasma membrane of eukaryotic cells is important for their correct cellular function, but the mechanisms by which GPI-APs are sorted are yet to be fully resolved. An extreme example of this is in African trypanosomes, where the major surface glycoprotein floods the whole cell surface while most GPI-APs are retained in a specialised domain at the base of the flagellum. One possibility is that anchor attachment signals direct differential sorting of proteins. To investigate this, we fused a monomeric reporter to the GPI-anchor insertion signals of trypanosome proteins that are differentially sorted on the plasma membrane. Fusions were correctly anchored by GPI, post-translationally modified, and routed to the plasma membrane, but this delivery was independent of retained signals upstream of the ω site. Instead, ω−minus signal strength appears key to efficacy of GPI addition and to GPI-AP cellular level. Thus, at least in this system, sorting is not encoded at the time of GPI anchor addition or in the insertion sequence retained in processed proteins. We discuss these findings in the context of previously proposed models for sorting mechanisms in trypanosomes.

将糖基磷脂酰肌醇锚定蛋白（GPI-APs）分离到真核细胞质膜上的不同区域对其正确的细胞功能非常重要，但 GPI-APs 的分离机制尚未完全确定。非洲锥虫就是一个极端的例子，它的主要表面糖蛋白遍布整个细胞表面，而大多数 GPI-AP 则保留在鞭毛基部的一个专门区域。一种可能性是，锚附着信号会引导蛋白质的不同分拣。为了研究这一点，我们将单体报告物与在质膜上进行不同分选的锥虫蛋白质的 GPI-锚插入信号融合。融合蛋白被 GPI 正确锚定、翻译后修饰并被输送到质膜上，但这种输送与 ω 位点上游的保留信号无关。相反，ω-minus 信号强度似乎是 GPI 添加效果和 GPI-AP 细胞水平的关键。因此，至少在这个系统中，分选不是在添加 GPI 锚点时编码的，也不是在加工蛋白中保留的插入序列中编码的。我们结合之前提出的锥虫分选机制模型讨论了这些发现。

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引用次数: 0

Study of fungal cell wall evolution through its monosaccharide composition: An insight into fungal species interacting with plants 通过单糖组成研究真菌细胞壁的进化：洞察与植物相互作用的真菌物种

Q1 Immunology and Microbiology

Cell Surface

Pub Date : 2024-06-01 DOI: 10.1016/j.tcsw.2024.100127

Sara I. Yugueros , Jorge Peláez , Jason E. Stajich , María Fuertes-Rabanal , Andrea Sánchez-Vallet , Asier Largo-Gosens , Hugo Mélida

Every fungal cell is encapsulated in a cell wall, essential for cell viability, morphogenesis, and pathogenesis. Most knowledge of the cell wall composition in fungi has focused on ascomycetes, especially human pathogens, but considerably less is known about early divergent fungal groups, such as species in the Zoopagomycota and Mucoromycota phyla. To shed light on evolutionary changes in the fungal cell wall, we studied the monosaccharide composition of the cell wall of 18 species including early diverging fungi and species in the Basidiomycota and Ascomycota phyla with a focus on those with pathogenic lifestyles and interactions with plants. Our data revealed that chitin is the most characteristic component of the fungal cell wall, and was found to be in a higher proportion in the early divergent groups. The Mucoromycota species possess few glucans, but instead have other monosaccharides such as fucose and glucuronic acid that are almost exclusively found in their cell walls. Additionally, we observed that hexoses (glucose, mannose and galactose) accumulate in much higher proportions in species belonging to Dikarya. Our data demonstrate a clear relationship between phylogenetic position and fungal cell wall carbohydrate composition and lay the foundation for a better understanding of their evolution and their role in plant interactions.

每个真菌细胞都包裹在细胞壁中，细胞壁对细胞存活、形态发生和致病至关重要。关于真菌细胞壁组成的大部分知识都集中在子囊菌，尤其是人类病原体上，但对于早期分化的真菌群，如紫真菌纲和粘菌纲的物种，人们的了解要少得多。为了揭示真菌细胞壁的进化变化，我们研究了 18 个物种细胞壁的单糖组成，其中包括早期分化的真菌以及担子菌门和子囊菌门中的物种，重点是那些具有致病生活方式并与植物有相互作用的真菌。我们的数据显示，几丁质是真菌细胞壁中最具特征性的成分，而且在早期分化的真菌群中所占比例较高。粘菌纲的物种几乎不含葡聚糖，而是在细胞壁中几乎只含有岩藻糖和葡萄糖醛酸等其他单糖。此外，我们还观察到，在属于 Dikarya 的物种中，己糖（葡萄糖、甘露糖和半乳糖）的积累比例要高得多。我们的数据证明了系统发育位置与真菌细胞壁碳水化合物组成之间的明确关系，为更好地了解真菌的进化及其在植物相互作用中的作用奠定了基础。

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