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Insights into Alphaproteobacterial regulators of cell envelope remodeling 细胞膜重塑的阿尔法蛋白细菌调控因子透视
IF 5.9 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-03 DOI: 10.1016/j.mib.2024.102538
Bryan Lakey , François Alberge , Timothy J Donohue

The cell envelope is at the center of many processes essential for bacterial lifestyles. In addition to giving bacteria shape and delineating it from the environment, it contains macromolecules important for energy transduction, cell division, protection against toxins, biofilm formation, or virulence. Hence, many systems coordinate different processes within the cell envelope to ensure function and integrity. Two-component systems have been identified as crucial regulators of cell envelope functions over the last few years. In this review, we summarize the new information obtained on the regulation of cell envelope biosynthesis and homeostasis in α-proteobacteria, as well as newly identified targets that coordinate the processes in the cell envelope.

细胞包膜是细菌生活方式所必需的许多过程的中心。除了赋予细菌形状并将其与环境区分开来之外,细胞包膜还含有对能量转换、细胞分裂、抵御毒素、生物膜形成或毒力很重要的大分子。因此,许多系统协调细胞包膜内的不同过程,以确保其功能和完整性。过去几年中,双组分系统已被确定为细胞包膜功能的关键调节因子。在这篇综述中,我们总结了有关α-蛋白细菌细胞包膜生物合成和平衡调控的新信息,以及新发现的协调细胞包膜过程的靶标。
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引用次数: 0
The yin and yang of the universal transcription factor NusG 通用转录因子 NusG 的阴与阳
IF 5.9 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-02 DOI: 10.1016/j.mib.2024.102540
Madeleine Delbeau , Ruby Froom , Robert Landick , Seth A Darst , Elizabeth A Campbell

RNA polymerase (RNAP), the central enzyme of transcription, intermittently pauses during the elongation stage of RNA synthesis. Pausing provides an opportunity for regulatory events such as nascent RNA folding or the recruitment of transregulators. NusG (Spt5 in eukaryotes and archaea) regulates RNAP pausing and is the only transcription factor conserved across all cellular life. NusG is a multifunctional protein: its N-terminal domain (NGN) binds to RNAP, and its C-terminal KOW domain in bacteria interacts with transcription regulators such as ribosomes and termination factors. In Escherichia coli, NusG acts as an antipausing factor. However, recent studies have revealed that NusG has distinct transcriptional regulatory roles specific to bacterial clades with clinical implications. Here, we focus on NusG’s dual roles in the regulation of pausing.

RNA 聚合酶(RNAP)是转录的核心酶,在 RNA 合成的延伸阶段会间歇性地暂停。暂停为新生 RNA 折叠或转录调节因子的招募等调节事件提供了机会。NusG(真核生物和古生菌中的 Spt5)调节 RNAP 的暂停,是所有细胞生命中唯一保留下来的转录因子。NusG 是一种多功能蛋白质:其 N 端结构域(NGN)与 RNAP 结合,在细菌中其 C 端 KOW 结构域与核糖体和终止因子等转录调节因子相互作用。在大肠杆菌中,NusG 起着抗停滞因子的作用。然而,最近的研究发现,NusG 在细菌支系中具有独特的转录调控作用,并具有临床意义。在此,我们将重点研究 NusG 在调控暂停过程中的双重作用。
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引用次数: 0
From dusty shelves toward the spotlight: growing evidence for Ap4A as an alarmone in maintaining RNA stability and proteostasis 从尘封的书架走向聚光灯下:越来越多的证据表明 Ap4A 是维持 RNA 稳定性和蛋白稳态的警报蛋白
IF 5.9 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-08-30 DOI: 10.1016/j.mib.2024.102536
Megan KM Young, Jue D Wang

Bacteria thrive in diverse environments and must withstand various stresses. A key stress response mechanism is the reprogramming of macromolecular biosynthesis and metabolic processes through alarmones — signaling nucleotides that accumulate intracellularly in response to metabolic stress. Diadenosine tetraphosphate (Ap4A), a putative alarmone, is produced in a noncanonical reaction by universally conserved aminoacyl-tRNA synthetases. Ap4A is ubiquitous across all domains of life and accumulates during heat and oxidative stress. Despite its early discovery in 1966, Ap4A’s alarmone status remained inconclusive. Recent discoveries identified Ap4A as a precursor to RNA 5′ caps in Escherichia coli. Additionally, Ap4A was found to directly bind to and allosterically inhibit the purine biosynthesis enzyme inosine 5′-monophosphate dehydrogenase, regulating guanosine triphosphate levels and enabling heat resistance in Bacillus subtilis. These findings, along with previous research, strongly suggest that Ap4A plays a crucial role as an alarmone, warranting further investigation to fully elucidate its functions.

细菌在各种环境中茁壮成长,必须承受各种压力。一种关键的应激反应机制是通过报警酮(一种信号核苷酸,在细胞内积累以应对代谢应激)对大分子生物合成和代谢过程进行重新编程。四磷酸二腺苷(Ap4A)是一种假定的警报素,由普遍保守的氨基酰-tRNA 合成酶在非规范反应中产生。Ap4A 在生命的各个领域都无处不在,并会在热和氧化应激时积累。尽管 Ap4A 早在 1966 年就已被发现,但其报警酮地位仍未确定。最近的研究发现,Ap4A 是大肠杆菌中 RNA 5′帽的前体。此外,研究还发现 Ap4A 可直接与嘌呤生物合成酶肌苷 5′-单磷酸脱氢酶结合,并对其产生异生抑制作用,从而调节三磷酸鸟苷的水平,使枯草芽孢杆菌具有耐热性。这些发现以及之前的研究都有力地表明,Ap4A 作为一种报警酮发挥着至关重要的作用,值得进一步研究以全面阐明其功能。
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引用次数: 0
Horizontal gene transfer and beyond: the delivery of biological matter by bacterial membrane vesicles to host and bacterial cells 横向基因转移及其他:细菌膜囊向宿主细胞和细菌细胞输送生物物质
IF 5.9 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-08-26 DOI: 10.1016/j.mib.2024.102525
Alice X Wen , Christophe Herman

Membrane vesicles (MVs) are produced in all domains of life. In eukaryotes, extracellular vesicles have been shown to mediate the horizontal transfer of biological material between cells [1]. Therefore, bacterial MVs are also thought to mediate horizontal material transfer to host cells and other bacteria, especially in the context of cell stress. In this review, we discuss the mechanisms of bacterial MV production, evidence that their contents can be trafficked to host cells and other bacteria, and the biological relevance of horizontal material transfer by bacterial MVs.

生命的各个领域都会产生膜囊泡。在真核生物中,细胞外囊泡已被证明可介导细胞间生物物质的水平转移[1]。因此,细菌的细胞外囊泡也被认为能介导向宿主细胞和其他细菌的水平物质转移,尤其是在细胞受压的情况下。在这篇综述中,我们将讨论细菌 MV 的产生机制、其内容物可被转运到宿主细胞和其他细菌的证据,以及细菌 MV 水平物质转运的生物学意义。
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引用次数: 0
Fungal effectors: past, present, and future 真菌效应器:过去、现在和未来
IF 5.9 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-08-23 DOI: 10.1016/j.mib.2024.102526
Gengtan Li , Madison Newman , Houlin Yu , Maryam Rashidzade , Domingo Martínez-Soto , Ana Caicedo , Kelly S Allen , Li-Jun Ma

Fungal effector proteins function at the interfaces of diverse interactions between fungi and their plant and animal hosts, facilitating interactions that are pathogenic or mutualistic. Recent advancements in protein structure prediction have significantly accelerated the identification and functional predictions of these rapidly evolving effector proteins. This development enables scientists to generate testable hypotheses for functional validation using experimental approaches. Research frontiers in effector biology include understanding pathways through which effector proteins are secreted or translocated into host cells, their roles in manipulating host microbiomes, and their contribution to interacting with host immunity. Comparative effector repertoires among different fungal–host interactions can highlight unique adaptations, providing insights for the development of novel antifungal therapies and biocontrol strategies.

真菌效应蛋白在真菌与其动植物宿主之间各种相互作用的界面上发挥作用,促进致病或互利的相互作用。蛋白质结构预测方面的最新进展大大加快了对这些快速进化的效应蛋白的鉴定和功能预测。这一进展使科学家们能够提出可检验的假设,并通过实验方法进行功能验证。效应蛋白生物学的研究前沿包括了解效应蛋白分泌或转运到宿主细胞的途径、它们在操纵宿主微生物组方面的作用以及它们在与宿主免疫相互作用方面的贡献。比较不同真菌-宿主相互作用的效应蛋白,可以突出独特的适应性,为开发新型抗真菌疗法和生物防治策略提供启示。
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引用次数: 0
D-galactonate metabolism in enteric bacteria: a molecular and physiological perspective 肠道细菌的 D-半乳糖醛酸代谢:分子和生理学视角。
IF 5.9 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-08-12 DOI: 10.1016/j.mib.2024.102524
Swati Singh , Chetna Gola , Bhupinder Singh , Vishal Agrawal , Rachna Chaba

D-galactonate, a widely prevalent sugar acid, was first reported as a nutrient source for enteric bacteria in the 1970s. Since then, decades of research enabled a description of the modified Entner-Doudoroff pathway involved in its degradation and reported the structural and biochemical features of its metabolic enzymes, primarily in Escherichia coli K-12. However, only in the last few years, the D-galactonate transporter has been characterized, and the regulation of the dgo operon, encoding the structural genes for the transporter and enzymes of D-galactonate metabolism, has been detailed. Notably, in recent years, multiple evolutionary studies have identified the dgo operon as a dominant target for adaptation of E. coli in the mammalian gut. Despite considerable research on dgo operon, numerous fundamental questions remain to be addressed. The emerging relevance of the dgo operon in host–bacterial interactions further necessitates the study of D-galactonate metabolism in other enterobacterial strains.

D -半乳糖酸是一种广泛存在的糖酸,在 20 世纪 70 年代首次被报道为肠道细菌的营养源。此后,经过数十年的研究,人们描述了参与降解 D-半乳糖醛酸的恩特纳-杜多罗夫(Entner-Doudoroff)改良途径,并报道了其代谢酶的结构和生化特征,主要是在大肠杆菌 K-12 中。然而,直到最近几年,D-半乳糖醛酸转运体的特征才得以确定,编码 D-半乳糖醛酸转运体结构基因和 D-半乳糖醛酸代谢酶的 dgo 操作子的调控也得到了详细说明。值得注意的是,近年来,多项进化研究发现,dgo 操作子是哺乳动物肠道中大肠杆菌适应的主要目标。尽管对 dgo 操作子进行了大量研究,但仍有许多基本问题有待解决。由于 dgo 操作子在宿主与细菌相互作用中的重要性不断显现,因此有必要进一步研究其他肠道细菌菌株的 D-半乳糖醛酸代谢。
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引用次数: 0
Host immune response against fungal biofilms 宿主对真菌生物膜的免疫反应。
IF 5.9 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-08-09 DOI: 10.1016/j.mib.2024.102520
Mohammad Mannan , Sunna Nabeela , Reetakshi Mishra , Priya Uppuluri

Fungal biofilms are a multilayered community of cells attached to mucosal or abiotic surfaces enclosed in a coating of self-produced extracellular polymeric matrix. The sheer density of cells protected by a polymeric shield not only makes the biofilm impermeable to antimicrobials or immune cells but also hidden from host recognition. Biofilms also serve as a reservoir of drug-resistant persister cells and dispersal cells armored with virulence factors adept at evading the immune system. Here, we summarize the latest knowledge on the immunomodulatory properties of biofilms formed by Candida species and by other biofilm-forming fungal pathogens such as Aspergillus and Cryptococcus. Finally, we deliberate on promising strategies to help activate the immune system for combating fungal biofilms.

真菌生物膜是附着在粘膜或非生物表面的多层细胞群落,其表面包裹着一层自身产生的胞外聚合物基质。在聚合基质保护下的高密度细胞不仅使生物膜无法被抗菌剂或免疫细胞渗透,而且也无法被宿主识别。生物膜还是抗药性持久细胞和散播细胞的储藏库,这些细胞具有善于躲避免疫系统的毒力因子。在此,我们总结了有关念珠菌和曲霉、隐球菌等其他形成生物膜的真菌病原体所形成的生物膜的免疫调节特性的最新知识。最后,我们探讨了有助于激活免疫系统以对抗真菌生物膜的可行策略。
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引用次数: 0
Editorial overview: emerging avenues in antimicrobial research 编辑综述:抗菌研究的新途径。
IF 5.9 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-08-07 DOI: 10.1016/j.mib.2024.102522
Toni Gabaldón , Luiz Pedro Sório de Carvalho
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引用次数: 0
Editorial overview: Coronaviruses 2024 编辑综述:冠状病毒 2024》。
IF 5.9 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-08-03 DOI: 10.1016/j.mib.2024.102523
Stephanie Pfaender , Eike Steinmann
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引用次数: 0
New developments in Aspergillus fumigatus and host reactive oxygen species responses 烟曲霉与宿主活性氧反应的新进展。
IF 5.9 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-08-01 DOI: 10.1016/j.mib.2024.102521
Matthew R James, Katherine E Doss, Robert A Cramer

Aspergillus fumigatus is a filamentous fungus abundant in the environment and the most common causative agent of a spectrum of human diseases collectively termed aspergillosis. Invasive pulmonary aspergillosis is caused by deficiencies in innate immune function that result in the inability of the host to clear inhaled Aspergillus conidia that then germinate and form invasive hyphae. Myeloid cells, and their ability to generate reactive oxygen species (ROS), are essential for conidia clearance from the host. To combat ROS, A. fumigatus employs an expansive antioxidant system, though how these canonical antioxidant mechanisms contribute to infection initiation and disease progression remain to be fully defined. Recent research has identified noncanonical pathways in the A. fumigatus ROS response and new host populations with ROS deficiencies that are at-risk for invasive aspergillosis. Here, we highlight recent developments in the understanding of ROS at the interface of the dynamic A. fumigatus–host interaction.

烟曲霉(Aspergillus fumigatus)是一种丝状真菌,在环境中大量存在,是一系列人类疾病(统称为曲霉病)最常见的致病菌。侵袭性肺曲霉菌病是由于先天性免疫功能缺陷导致宿主无法清除吸入的曲霉菌分生孢子,分生孢子发芽后形成侵袭性菌丝而引起的。髓细胞及其产生活性氧(ROS)的能力对于从宿主体内清除分生孢子至关重要。为了对抗 ROS,烟曲霉使用了一种广泛的抗氧化系统,但这些典型的抗氧化机制如何促进感染的发生和疾病的发展仍有待全面界定。最近的研究发现了烟曲霉 ROS 反应中的非经典途径,以及存在 ROS 缺陷的新宿主群体,这些宿主面临着侵袭性曲霉病的风险。在此,我们重点介绍在烟曲霉与宿主动态相互作用的界面上了解 ROS 的最新进展。
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引用次数: 0
期刊
Current opinion in microbiology
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