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Determinants of bacterial survival and proliferation in blood. 细菌在血液中存活和增殖的决定因素。
IF 11.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-05-08 DOI: 10.1093/femsre/fuae013
Pierre Lê-Bury, Hebert Echenique-Rivera, Javier Pizarro-Cerdá, Olivier Dussurget

Bloodstream infection is a major public health concern associated with high mortality and high healthcare costs worldwide. Bacteremia can trigger fatal sepsis whose prevention, diagnosis, and management have been recognized as a global health priority by the World Health Organization. Additionally, infection control is increasingly threatened by antimicrobial resistance, which is the focus of global action plans in the framework of a One Health response. In-depth knowledge of the infection process is needed to develop efficient preventive and therapeutic measures. The pathogenesis of bloodstream infection is a dynamic process resulting from the invasion of the vascular system by bacteria, which finely regulate their metabolic pathways and virulence factors to overcome the blood immune defenses and proliferate. In this review, we highlight our current understanding of determinants of bacterial survival and proliferation in the bloodstream and discuss their interactions with the molecular and cellular components of blood.

血流感染是一个重大的公共卫生问题,在全球造成高死亡率和高医疗成本。菌血症可引发致命的败血症,其预防、诊断和管理已被世界卫生组织视为全球健康的优先事项。此外,感染控制正日益受到抗菌素耐药性的威胁,这也是 "一个健康 "应对框架下全球行动计划的重点。要制定有效的预防和治疗措施,就必须深入了解感染过程。血流感染的发病机制是一个动态过程,由细菌入侵血管系统引起,细菌精细调节其代谢途径和毒力因子,以克服血液免疫防御系统并进行增殖。在这篇综述中,我们将重点介绍我们目前对细菌在血液中存活和增殖的决定因素的理解,并讨论它们与血液分子和细胞成分的相互作用。
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引用次数: 0
Epitopes in the HA and NA of H5 and H7 avian influenza viruses that are important for antigenic drift. 对抗原漂移至关重要的 H5 和 H7 禽流感病毒 HA 和 NA 表位。
IF 10.1 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-05-08 DOI: 10.1093/femsre/fuae014
Jasmina M Luczo, Erica Spackman

Avian influenza viruses evolve antigenically to evade host immunity. Two influenza A virus surface glycoproteins, the haemagglutinin and neuraminidase, are the major targets of host immunity and undergo antigenic drift in response to host pre-existing humoral and cellular immune responses. Specific sites have been identified as important epitopes in prominent subtypes such as H5 and H7, which are of animal and public health significance due to their panzootic and pandemic potential. The haemagglutinin is the immunodominant immunogen, it has been extensively studied, and the antigenic reactivity is closely monitored to ensure candidate vaccine viruses are protective. More recently, the neuraminidase has received increasing attention for its role as a protective immunogen. The neuraminidase is expressed at a lower abundance than the haemagglutinin on the virus surface but does elicit a robust antibody response. This review aims to compile the current information on haemagglutinin and neuraminidase epitopes and immune escape mutants of H5 and H7 highly pathogenic avian influenza viruses. Understanding the evolution of immune escape mutants and the location of epitopes is critical for identification of vaccine strains and development of broadly reactive vaccines that can be utilized in humans and animals.

禽流感病毒通过抗原进化来逃避宿主免疫。两种甲型流感病毒表面糖蛋白--血凝素和神经氨酸酶--是宿主免疫的主要目标,并在宿主原有体液和细胞免疫反应的作用下发生抗原漂移。特定位点已被确定为 H5 和 H7 等主要亚型的重要表位,这些亚型具有泛滥和大流行的潜能,对动物和公共卫生具有重要意义。血凝素是免疫优势免疫原,已对其进行了广泛研究,并对抗原反应性进行了密切监测,以确保候选疫苗病毒具有保护性。最近,神经氨酸酶作为一种保护性免疫原受到越来越多的关注。与病毒表面的血凝素相比,神经氨酸酶的表达量较低,但却能引起强大的抗体反应。本综述旨在汇编有关 H5 和 H7 高致病性禽流感病毒血凝素和神经氨酸酶表位及免疫逃逸突变体的现有信息。了解免疫逃逸突变体的进化和表位的位置对于确定疫苗株和开发可用于人类和动物的广谱反应疫苗至关重要。
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引用次数: 0
Diving into drug-screening: Zebrafish Embryos as an in vivo Platform for Antimicrobial Drug Discovery and Assessment 潜入药物筛选:斑马鱼胚胎作为抗菌药物发现和评估的体内平台
IF 11.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-04-30 DOI: 10.1093/femsre/fuae011
Eva Habjan, Gina K Schouten, Alexander Speer, Peter van Ulsen, Wilbert Bitter
The rise of multidrug-resistant bacteria underlines the need for innovative treatments, yet the introduction of new drugs has stagnated despite numerous antimicrobial discoveries. A major hurdle is a poor correlation between promising in vitro data and in vivo efficacy in animal models, which is essential for clinical development. Early in vivo testing is hindered by the expense and complexity of existing animal models. Therefore, there is a pressing need for cost-effective, rapid pre-clinical models with high translational value. To overcome these challenges, zebrafish embryos have emerged as an attractive model for infectious disease studies, offering advantages such as ethical alignment, rapid development, ease of maintenance, and genetic manipulability. The zebrafish embryo infection model, involving microinjection or immersion of pathogens and potential antibiotic hit compounds, provides a promising solution for early-stage drug screening. It offers a cost-effective and rapid means of assessing the efficacy, toxicity and mechanism of action of compounds in a whole-organism context. This review discusses the experimental design of this model, but also its benefits and challenges. Additionally, it highlights recently identified compounds in the zebrafish embryo infection model and discusses the relevance of the model in predicting the compound's clinical potential.
耐多药细菌的增多凸显了对创新疗法的需求,然而,尽管抗菌药物的发现层出不穷,新药的推出却停滞不前。一个主要障碍是,有前景的体外数据与动物模型体内疗效之间的相关性很差,而动物模型体内疗效对临床开发至关重要。现有动物模型的费用和复杂性阻碍了早期体内试验。因此,迫切需要具有高转化价值的经济、快速的临床前模型。为了克服这些挑战,斑马鱼胚胎已成为一种极具吸引力的传染病研究模型,它具有符合道德规范、开发迅速、易于维护和遗传可操作性强等优点。斑马鱼胚胎感染模型涉及病原体和潜在抗生素化合物的显微注射或浸泡,为早期药物筛选提供了一种前景广阔的解决方案。它为在整个生物体内评估化合物的药效、毒性和作用机制提供了一种经济、快速的方法。本综述讨论了这一模型的实验设计,以及它的优势和挑战。此外,它还重点介绍了最近在斑马鱼胚胎感染模型中发现的化合物,并讨论了该模型在预测化合物临床潜力方面的相关性。
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引用次数: 0
An opportunistic pathogen under stress: how group B streptococcus responds to cytotoxic reactive species and conditions of metal ion imbalance to survive 压力下的机会性病原体:B 组链球菌如何应对细胞毒性反应物和金属离子失衡条件以求生存
IF 11.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-04-27 DOI: 10.1093/femsre/fuae009
Kelvin G K Goh, Devika Desai, Ruby Thapa, Darren Prince, Dhruba Acharya, Matthew J Sullivan, Glen C Ulett
Group B Streptococcus (GBS; also known as Streptococcus agalactiae) is an opportunistic bacterial pathogen that causes sepsis, meningitis, pneumonia and skin and soft tissue infections in neonates and healthy or immunocompromised adults. GBS is well-adapted to survive in humans due to a plethora of virulence mechanisms that afford responses to support bacterial survival in dynamic host environments. These mechanisms and responses include counteraction of cell death from exposure to excess metal ions that can cause mismetallation and cytotoxicity, and strategies to combat molecules such as reactive oxygen and nitrogen species that are generated as part of innate host defence. Cytotoxicity from reactive molecules can stem from damage to proteins, DNA, and membrane lipids, potentially leading to bacterial cell death inside phagocytic cells or within extracellular spaces within the host. Deciphering the ways in which GBS responds to the stress of cytotoxic reactive molecules within the host will benefit the development of novel therapeutic and preventative strategies to manage the burden of GBS disease. This review summarises knowledge of GBS carriage in humans and the mechanisms used by the bacteria to circumvent killing by these important elements of host immune defence: oxidative stress, nitrosative stress, and stress from metal ion intoxication/mismetallation.
B 群链球菌(GBS,又称无乳链球菌)是一种机会性细菌病原体,可导致新生儿、健康或免疫力低下的成年人发生败血症、脑膜炎、肺炎以及皮肤和软组织感染。由于具有大量的毒力机制,GBS 非常适合在人体内生存,这些机制提供了支持细菌在动态宿主环境中生存的反应。这些机制和反应包括抵御因暴露于过量金属离子而导致的细胞死亡(金属离子可导致误杀和细胞毒性),以及抵御活性氧和氮物种等分子的策略,这些分子是宿主先天防御的一部分。活性分子产生的细胞毒性可能源于对蛋白质、DNA 和膜脂的破坏,有可能导致细菌细胞在吞噬细胞内或宿主体内的细胞外空间死亡。破译 GBS 如何应对宿主体内细胞毒性反应分子的压力,将有助于开发新型治疗和预防策略,控制 GBS 疾病的负担。本综述总结了人类携带 GBS 的知识,以及细菌用于规避宿主免疫防御重要因素(氧化应激、亚硝酸应激和金属离子中毒/失活应激)杀灭的机制。
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引用次数: 0
Louis Pasteur, a child of the Jura, a man for the world 路易-巴斯德,一个汝拉的孩子,一个为世界而生的人
IF 11.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-04-25 DOI: 10.1093/femsre/fuae010
Daniel Raichvarg, Tomasz Jagielski
How did Louis Pasteur, born in a small town in the Jura—Dole, still little known to the world today, become a man of global recognition and fame? The answer to this question is guided by two pivotal considerations. First is Pasteur's relationship to the representation of reality. This relationship was seeded and steadily developed since his juvenile years through practicing different forms of artistic expression, the most famous of which were subtle pastels portraying Pasteur's parents and neighbors. This genuine attraction towards art gradually became «scientificized» at the same time, when new means of reproducing the reality were invented, such as photography. The second consideration, critical to understand the phenomenon of Pasteur's celebrity, is a strong linkage of his research with nature-based agricultural production. Here again, deeply rooted in his youth and home environment, permeated with the taste of wine and the smell of tanned leather, Pasteur's interests necessitated the processes of communication, not only at the scientific level, but also on a daily life basis, with numerous «social actors» at play (ferments, silkworms etc.). Throughout his work, Pasteur had to provide himself with the means to set up these interdisciplinarity and communication. The final result was the Pasteur Institute, or rather the Pasteur Institutes and the global Pasteur network.
路易-巴斯德出生于汝拉-多勒的一个小镇,至今仍鲜为人知,他是如何成为一个享誉全球的人物的呢?这个问题的答案取决于两个关键因素。首先是巴斯德与现实表象的关系。这种关系从他少年时代就开始了,并通过不同形式的艺术表现实践稳步发展,其中最著名的是描绘巴斯德父母和邻居的细腻粉彩画。与此同时,随着摄影等再现现实的新手段的发明,这种对艺术的真正吸引力逐渐 "科学化"。第二点对于理解巴斯德的名人现象至关重要,那就是他的研究与以自然为基础的农业生产密切相关。同样,巴斯德的兴趣深深植根于他的青年时代和家庭环境,渗透着葡萄酒的味道和鞣革的气味,他的兴趣需要交流的过程,不仅在科学层面,而且在日常生活中,也有许多 "社会角色 "在发挥作用(发酵、养蚕等)。在巴斯德的整个工作过程中,他必须为自己提供建立这些跨学科和交流的手段。最终的成果就是巴斯德研究所,或者说是巴斯德研究所和全球巴斯德网络。
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引用次数: 0
In vitro modelling of bacterial pneumonia: a comparative analysis of widely applied complex cell culture models. 细菌性肺炎的体外模型:对广泛应用的复杂细胞培养模型的比较分析。
IF 11.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-03-01 DOI: 10.1093/femsre/fuae007
Laure Mahieu, Laurence Van Moll, Linda De Vooght, Peter Delputte, Paul Cos

Bacterial pneumonia greatly contributes to the disease burden and mortality of lower respiratory tract infections among all age groups and risk profiles. Therefore, laboratory modelling of bacterial pneumonia remains important for elucidating the complex host-pathogen interactions and to determine drug efficacy and toxicity. In vitro cell culture enables for the creation of high-throughput, specific disease models in a tightly controlled environment. Advanced human cell culture models specifically, can bridge the research gap between the classical two-dimensional cell models and animal models. This review provides an overview of the current status of the development of complex cellular in vitro models to study bacterial pneumonia infections, with a focus on air-liquid interface models, spheroid, organoid, and lung-on-a-chip models. For the wide scale, comparative literature search, we selected six clinically highly relevant bacteria (Pseudomonas aeruginosa, Mycoplasma pneumoniae, Haemophilus influenzae, Mycobacterium tuberculosis, Streptococcus pneumoniae, and Staphylococcus aureus). We reviewed the cell lines that are commonly used, as well as trends and discrepancies in the methodology, ranging from cell infection parameters to assay read-outs. We also highlighted the importance of model validation and data transparency in guiding the research field towards more complex infection models.

细菌性肺炎在各年龄段和各种风险特征的下呼吸道感染疾病负担和死亡率中占很大比例。因此,细菌性肺炎的实验室建模对于阐明复杂的宿主-病原体相互作用以及确定药物疗效和毒性仍然非常重要。体外细胞培养可以在严格控制的环境中建立高通量的特定疾病模型。特别是先进的人类细胞培养模型,可以弥补经典二维细胞模型和动物模型之间的研究差距。本综述概述了研究细菌性肺炎感染的复杂细胞体外模型的发展现状,重点介绍了气液界面模型、球形模型、类器官模型和芯片肺模型。在广泛的比较性文献检索中,我们选择了六种临床高度相关的细菌(铜绿假单胞菌、肺炎双球菌、流感嗜血杆菌、结核杆菌、肺炎双球菌和金黄色葡萄球菌)。我们回顾了常用的细胞系,以及从细胞感染参数到检测读数等方法的趋势和差异。我们还强调了模型验证和数据透明度对指导研究领域建立更复杂感染模型的重要性。
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引用次数: 0
Life at the borderlands: microbiomes of interfaces critical to One Health. 边境地区的生命:对 "一体健康 "至关重要的界面微生物组。
IF 11.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-03-01 DOI: 10.1093/femsre/fuae008
Simon R Law, Falko Mathes, Amy M Paten, Pamela A Alexandre, Roshan Regmi, Cameron Reid, Azadeh Safarchi, Shaktivesh Shaktivesh, Yanan Wang, Annaleise Wilson, Scott A Rice, Vadakattu V S R Gupta

Microbiomes are foundational components of the environment that provide essential services relating to food security, carbon sequestration, human health, and the overall well-being of ecosystems. Microbiota exert their effects primarily through complex interactions at interfaces with their plant, animal, and human hosts, as well as within the soil environment. This review aims to explore the ecological, evolutionary, and molecular processes governing the establishment and function of microbiome-host relationships, specifically at interfaces critical to One Health-a transdisciplinary framework that recognizes that the health outcomes of people, animals, plants, and the environment are tightly interconnected. Within the context of One Health, the core principles underpinning microbiome assembly will be discussed in detail, including biofilm formation, microbial recruitment strategies, mechanisms of microbial attachment, community succession, and the effect these processes have on host function and health. Finally, this review will catalogue recent advances in microbiology and microbial ecology methods that can be used to profile microbial interfaces, with particular attention to multi-omic, advanced imaging, and modelling approaches. These technologies are essential for delineating the general and specific principles governing microbiome assembly and functions, mapping microbial interconnectivity across varying spatial and temporal scales, and for the establishment of predictive frameworks that will guide the development of targeted microbiome-interventions to deliver One Health outcomes.

微生物群是环境的基础组成部分,为粮食安全、碳固存、人类健康和生态系统的整体福祉提供重要服务。微生物群主要通过与其植物、动物和人类宿主以及土壤环境之间复杂的相互作用来发挥其作用。本综述旨在探讨微生物群-宿主关系的建立和功能的生态、进化和分子过程,特别是在对 "一体健康 "至关重要的界面上。"一体健康 "是一个跨学科框架,它认为人、动物、植物和环境的健康结果是紧密相连的。在 "一体健康 "的背景下,将详细讨论微生物组组合的核心原则,包括生物膜形成、微生物招募策略、微生物附着机制、群落演替以及这些过程对宿主功能和健康的影响。最后,本综述将介绍微生物学和微生物生态学方法的最新进展,这些方法可用于剖析微生物界面,尤其关注多组学、高级成像和建模方法。这些技术对于确定微生物组组装和功能的一般和特定原则、绘制不同时空尺度的微生物相互联系图以及建立预测框架至关重要,这些框架将指导有针对性的微生物组干预措施的开发,从而实现 "一体健康 "的结果。
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引用次数: 0
Evolution and emergence of Mycobacterium tuberculosis. 结核分枝杆菌的进化和出现。
IF 10.1 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-03-01 DOI: 10.1093/femsre/fuae006
Mickael Orgeur, Camille Sous, Jan Madacki, Roland Brosch

Tuberculosis (TB) remains one of the deadliest infectious diseases in human history, prevailing even in the 21st century. The causative agents of TB are represented by a group of closely related bacteria belonging to the Mycobacterium tuberculosis complex (MTBC), which can be subdivided into several lineages of human- and animal-adapted strains, thought to have shared a last common ancestor emerged by clonal expansion from a pool of recombinogenic Mycobacterium canettii-like tubercle bacilli. A better understanding of how MTBC populations evolved from less virulent mycobacteria may allow for discovering improved TB control strategies and future epidemiologic trends. In this review, we highlight new insights into the evolution of mycobacteria at the genus level, describing different milestones in the evolution of mycobacteria, with a focus on the genomic events that have likely enabled the emergence and the dominance of the MTBC. We also review the recent literature describing the various MTBC lineages and highlight their particularities and differences with a focus on host preferences and geographic distribution. Finally, we discuss on putative mechanisms driving the evolution of tubercle bacilli and mycobacteria in general, by taking the mycobacteria-specific distributive conjugal transfer as an example.

结核病(TB)仍然是人类历史上最致命的传染病之一,甚至在 21 世纪仍在流行。结核病的致病菌是一组密切相关的细菌,属于结核分枝杆菌复合体(MTBC),可细分为几个适应人类和动物的菌株系,据认为它们的最后共同祖先是从卡奈特分枝杆菌类似结核杆菌的重组菌群中通过克隆扩增而出现的。更好地了解 MTBC 群体是如何从毒性较弱的分枝杆菌进化而来的,有助于发现更好的结核病控制策略和未来的流行趋势。在这篇综述中,我们重点介绍了在属一级对分枝杆菌进化的新认识,描述了分枝杆菌进化过程中的不同里程碑,重点关注可能促成 MTBC 出现并占据主导地位的基因组事件。我们还回顾了描述 MTBC 各系的最新文献,并着重介绍了它们的特性和差异,重点是宿主偏好和地理分布。最后,我们以分枝杆菌特异性分布式共轭传递为例,讨论了推动结核杆菌和分枝杆菌进化的可能机制。
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引用次数: 0
Towards a rational approach to promoter engineering: understanding the complexity of transcription initiation in prokaryotes. 启动子工程的合理方法:了解原核生物转录启动的复杂性。
IF 11.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-03-01 DOI: 10.1093/femsre/fuae004
Cara Deal, Lien De Wannemaeker, Marjan De Mey

Promoter sequences are important genetic control elements. Through their interaction with RNA polymerase they determine transcription strength and specificity, thereby regulating the first step in gene expression. Consequently, they can be targeted as elements to control predictability and tuneability of a genetic circuit, which is essential in applications such as the development of robust microbial cell factories. This review considers the promoter elements implicated in the three stages of transcription initiation, detailing the complex interplay of sequence-specific interactions that are involved, and highlighting that DNA sequence features beyond the core promoter elements work in a combinatorial manner to determine transcriptional strength. In particular, we emphasize that, aside from promoter recognition, transcription initiation is also defined by the kinetics of open complex formation and promoter escape, which are also known to be highly sequence specific. Significantly, we focus on how insights into these interactions can be manipulated to lay the foundation for a more rational approach to promoter engineering.

启动子序列是重要的基因控制元件。它们通过与 RNA 聚合酶的相互作用决定转录强度和特异性,从而调节基因表达的第一步。因此,启动子序列可以作为控制遗传回路可预测性和可调控性的目标元件,这在开发强大的微生物细胞工厂等应用中至关重要。本综述探讨了与转录启动三个阶段有关的启动子元件,详细介绍了其中涉及的序列特异性相互作用的复杂相互作用,并强调了核心启动子元件以外的 DNA 序列特征以组合方式决定转录强度。我们特别强调,除了启动子识别之外,转录启动还取决于开放复合物形成和启动子逸出的动力学,众所周知,这也具有高度的序列特异性。重要的是,我们将重点关注如何利用对这些相互作用的了解,为更合理的启动子工程学方法奠定基础。
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引用次数: 0
Radioactive waste microbiology: predicting microbial survival and activity in changing extreme environments. 放射性废物微生物学:预测微生物在不断变化的极端环境中的生存和活动。
IF 11.3 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-01-12 DOI: 10.1093/femsre/fuae001
Simon P Gregory, Jessica R M Mackie, Megan J Barnett

The potential for microbial activity to occur within the engineered barrier system (EBS) of a geological disposal facility (GDF) for radioactive waste is acknowledged by waste management organizations as it could affect many aspects of the safety functions of a GDF. Microorganisms within an EBS will be exposed to changing temperature, pH, radiation, salinity, saturation, and availability of nutrient and energy sources, which can limit microbial survival and activity. Some of the limiting conditions are incorporated into GDF designs for safety reasons, including the high pH of cementitious repositories, the limited pore space of bentonite-based repositories, or the high salinity of GDFs in evaporitic geologies. Other environmental conditions such as elevated radiation, temperature, and desiccation, arise as a result of the presence of high heat generating waste (HHGW). Here, we present a comprehensive review of how environmental conditions in the EBS may limit microbial activity, covering HHGW and lower heat generating waste (LHGW) in a range of geological environments. We present data from the literature on the currently recognized limits to life for each of the environmental conditions described above, and nutrient availability to establish the potential for life in these environments. Using examples where each variable has been modelled for a particular GDF, we outline the times and locations when that variable can be expected to limit microbial activity. Finally, we show how this information for multiple variables can be used to improve our understanding of the potential for microbial activity to occur within the EBS of a GDF and, more broadly, to understand microbial life in changing environments exposed to multiple extreme conditions.

放射性废物地质处置设施(GDF)的工程屏障系统(EBS)内可能会出现微生物活动,这一点已得到废物管理机构的认可,因为它有可能影响 GDF 安全功能的许多方面。EBS 中的微生物将暴露于不断变化的温度、pH 值、辐射、盐度、饱和度以及营养和能量来源的可用性,这些都可能限制微生物的生存和活动。出于安全考虑,一些限制条件被纳入了 GDF 设计,包括:水泥基储存库的高 pH 值、膨润土基储存库的有限孔隙空间或蒸发地质中 GDF 的高盐度。高发热废物(HHGW)的存在还会导致辐射、温度和干燥等其他环境条件的升高。在此,我们对 EBS 中的环境条件如何限制微生物活动进行了全面回顾,涵盖了一系列地质环境中的高发热量废物和低发热量废物 (LHGW)。我们介绍了文献中关于上述每种环境条件下目前公认的生命极限的数据,以及养分可用性,以确定这些环境中的生命潜力。通过对特定 GDF 的每个变量进行建模的例子,我们概述了该变量预计会限制微生物活动的时间和地点。最后,我们展示了如何利用这些有关多个变量的信息来提高我们对全球饵料发展基金 EBS 中微生物活动潜力的理解,以及更广泛地理解暴露于多种极端条件下的变化环境中的微生物生命。
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引用次数: 0
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