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Mechanisms of host adaptation by bacterial pathogens. 细菌病原体适应宿主的机制。
IF 10.1 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-06-20 DOI: 10.1093/femsre/fuae019
Matthew F Barber, J Ross Fitzgerald

The emergence of new infectious diseases poses a major threat to humans, animals, and broader ecosystems. Defining factors that govern the ability of pathogens to adapt to new host species is therefore a crucial research imperative. Pathogenic bacteria are of particular concern, given dwindling treatment options amid the continued expansion of antimicrobial resistance. In this review, we summarize recent advancements in the understanding of bacterial host species adaptation, with an emphasis on pathogens of humans and related mammals. We focus particularly on molecular mechanisms underlying key steps of bacterial host adaptation including colonization, nutrient acquisition, and immune evasion, as well as suggest key areas for future investigation. By developing a greater understanding of the mechanisms of host adaptation in pathogenic bacteria, we may uncover new strategies to target these microbes for the treatment and prevention of infectious diseases in humans, animals, and the broader environment.

新传染病的出现对人类、动物和更广泛的生态系统构成了重大威胁。因此,确定制约病原体适应新宿主物种能力的因素是一项至关重要的研究任务。随着抗菌药耐药性的不断扩大,治疗方法也越来越少,因此致病细菌尤其令人担忧。在这篇综述中,我们总结了对细菌宿主物种适应性认识的最新进展,重点是人类和相关哺乳动物的病原体。我们特别关注细菌宿主适应的关键步骤(包括定殖、营养获取和免疫逃避)的分子机制,并提出了未来研究的关键领域。通过进一步了解致病细菌宿主适应的基本机制,我们可能会发现针对这些微生物的新策略,从而治疗和预防人类、动物和更广泛环境中的传染性疾病。
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引用次数: 0
Host-bacteria interactions: ecological and evolutionary insights from ancient, professional endosymbionts. 宿主与细菌之间的相互作用:从古老的专业内共生菌中获得的生态学和进化论启示。
IF 10.1 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-06-20 DOI: 10.1093/femsre/fuae021
Zélia Bontemps, Kiran Paranjape, Lionel Guy

Interactions between eukaryotic hosts and their bacterial symbionts drive key ecological and evolutionary processes, from regulating ecosystems to the evolution of complex molecular machines and processes. Over time, endosymbionts generally evolve reduced genomes, and their relationship with their host tends to stabilize. However, host-bacteria relationships may be heavily influenced by environmental changes. Here, we review these effects on one of the most ancient and diverse endosymbiotic groups, formed by-among others-Legionellales, Francisellaceae, and Piscirickettsiaceae. This group is referred to as Deep-branching Intracellular Gammaproteobacteria (DIG), whose last common ancestor presumably emerged about 2 Ga ago. We show that DIGs are globally distributed, but generally at very low abundance, and are mainly identified in aquatic biomes. Most DIGs harbour a type IVB secretion system, critical for host-adaptation, but its structure and composition vary. Finally, we review the different types of microbial interactions that can occur in diverse environments, with direct or indirect effects on DIG populations. The increased use of omics technologies on environmental samples will allow a better understanding of host-bacterial interactions and help unravel the definition of DIGs as a group from an ecological, molecular, and evolutionary perspective.

真核生物宿主与其细菌共生体之间的相互作用推动着从调节生态系统到复杂分子机器和过程的进化等关键的生态和进化过程。随着时间的推移,内共生菌通常会进化出更小的基因组,它们与宿主的关系也趋于稳定。然而,宿主与细菌的关系可能会受到环境变化的严重影响。在这里,我们回顾了这些影响对一个最古老、最多样化的内共生菌群的影响,该菌群由军团菌科、弗朗西斯菌科和鱼腥草菌科等组成。该菌群被称为深分支胞内伽马蛋白菌(DIG),其最后的共同祖先可能出现在大约 20 亿年前。我们的研究表明,DIG 在全球都有分布,但一般含量很低,主要在水生生物群落中发现。大多数 DIGs 都有一个 IVB 型分泌系统,这对宿主适应至关重要,但其结构和组成各不相同。最后,我们回顾了在不同环境中可能发生的不同类型的微生物相互作用,它们对 DIG 种群有着直接或间接的影响。在环境样本中越来越多地使用 omics 技术将有助于更好地了解宿主与细菌之间的相互作用,并有助于从生态、分子和进化的角度揭示 DIG 作为一个群体的定义。
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引用次数: 0
Unravelling the mechanisms of antibiotic and heavy metal resistance co-selection in environmental bacteria. 揭示环境细菌中抗生素和重金属抗药性共同选择的机制。
IF 10.1 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-06-20 DOI: 10.1093/femsre/fuae017
Brodie F Gillieatt, Nicholas V Coleman

The co-selective pressure of heavy metals is a contributor to the dissemination and persistence of antibiotic resistance genes in environmental reservoirs. The overlapping range of antibiotic and metal contamination and similarities in their resistance mechanisms point to an intertwined evolutionary history. Metal resistance genes are known to be genetically linked to antibiotic resistance genes, with plasmids, transposons, and integrons involved in the assembly and horizontal transfer of the resistance elements. Models of co-selection between metals and antibiotics have been proposed, however, the molecular aspects of these phenomena are in many cases not defined or quantified and the importance of specific metals, environments, bacterial taxa, mobile genetic elements, and other abiotic or biotic conditions are not clear. Co-resistance is often suggested as a dominant mechanism, but interpretations are beset with correlational bias. Proof of principle examples of cross-resistance and co-regulation has been described but more in-depth characterizations are needed, using methodologies that confirm the functional expression of resistance genes and that connect genes with specific bacterial hosts. Here, we comprehensively evaluate the recent evidence for different models of co-selection from pure culture and metagenomic studies in environmental contexts and we highlight outstanding questions.

重金属的共同选择压力是抗生素抗性基因在环境库中传播和持续存在的一个因素。抗生素和金属污染的重叠范围及其抗药性机制的相似性表明,两者的进化历史是交织在一起的。众所周知,金属抗性基因与抗生素抗性基因之间存在基因联系,质粒、转座子和整合子参与了抗性元件的组装和水平转移。有人提出了金属与抗生素共同选择的模型,但在许多情况下,这些现象的分子方面并没有确定或量化,特定金属、环境、细菌类群、移动遗传因子以及其他非生物或生物条件的重要性也不明确。共同抗性通常被认为是一种主要机制,但在解释时存在相关性偏差。已有交叉抗性和共同调控的原理性实例被描述,但还需要使用能确认抗性基因的功能性表达以及能将基因与特定细菌宿主联系起来的方法,对其特征进行更深入的描述。在此,我们全面评估了最近从环境背景下的纯培养和元基因组研究中获得的不同共选模式的证据,并强调了悬而未决的问题。
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引用次数: 0
The vast landscape of carbohydrate fermentation in prokaryotes. 原核生物碳水化合物发酵的广阔前景
IF 10.1 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-06-20 DOI: 10.1093/femsre/fuae016
Timothy J Hackmann

Fermentation is a type of metabolism carried out by organisms in environments without oxygen. Despite being studied for over 185 years, the diversity and complexity of this metabolism are just now becoming clear. Our review starts with the definition of fermentation, which has evolved over the years and which we help further refine. We then examine the range of organisms that carry out fermentation and their traits. Over one-fourth of all prokaryotes are fermentative, use more than 40 substrates, and release more than 50 metabolic end products. These insights come from studies analyzing records of thousands of organisms. Next, our review examines the complexity of fermentation at the biochemical level. We map out pathways of glucose fermentation in unprecedented detail, covering over 120 biochemical reactions. We also review recent studies coupling genomics and enzymology to reveal new pathways and enzymes. Our review concludes with practical applications for agriculture, human health, and industry. All these areas depend on fermentation and could be improved through manipulating fermentative microbes and enzymes. We discuss potential approaches for manipulation, including genetic engineering, electrofermentation, probiotics, and enzyme inhibitors. We hope our review underscores the importance of fermentation research and stimulates the next 185 years of study.

发酵是生物在无氧环境中进行的一种新陈代谢。尽管对发酵的研究已经超过 185 年,但这种新陈代谢的多样性和复杂性现在才逐渐清晰起来。我们的综述从发酵的定义开始,该定义经过多年演变,我们将帮助进一步完善。然后,我们研究了进行发酵的生物种类及其特征。超过 1/4 的原核生物都具有发酵功能,使用 40 多种底物,并释放出 50 多种代谢终产物。这些见解来自对数千种生物记录的分析研究。接下来,我们将从生化层面探讨发酵的复杂性。我们以前所未有的细节描绘了葡萄糖发酵的途径,涵盖 120 多个生化反应。我们还回顾了最近将基因组学和酶学结合起来以揭示新途径和新酶的研究。最后,我们介绍了葡萄糖在农业、人类健康和工业中的实际应用。所有这些领域都依赖于发酵,可以通过操纵发酵微生物和酶来加以改进。我们讨论了潜在的操作方法,包括基因工程、电发酵、益生菌和酶抑制剂。我们希望我们的综述能强调发酵研究的重要性,并激励下一个 185 年的研究。
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引用次数: 0
Escherichia coli DNA replication: the old model organism still holds many surprises. 大肠杆菌的 DNA 复制:这一古老的模式生物仍有许多惊喜。
IF 10.1 2区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-06-20 DOI: 10.1093/femsre/fuae018
Krystian Łazowski, Roger Woodgate, Iwona J Fijalkowska

Research on Escherichia coli DNA replication paved the groundwork for many breakthrough discoveries with important implications for our understanding of human molecular biology, due to the high level of conservation of key molecular processes involved. To this day, it attracts a lot of attention, partially by virtue of being an important model organism, but also because the understanding of factors influencing replication fidelity might be important for studies on the emergence of antibiotic resistance. Importantly, the wide access to high-resolution single-molecule and live-cell imaging, whole genome sequencing, and cryo-electron microscopy techniques, which were greatly popularized in the last decade, allows us to revisit certain assumptions about the replisomes and offers very detailed insight into how they work. For many parts of the replisome, step-by-step mechanisms have been reconstituted, and some new players identified. This review summarizes the latest developments in the area, focusing on (a) the structure of the replisome and mechanisms of action of its components, (b) organization of replisome transactions and repair, (c) replisome dynamics, and (d) factors influencing the base and sugar fidelity of DNA synthesis.

对大肠杆菌 DNA 复制的研究为许多突破性发现奠定了基础,这些发现对我们了解人类分子生物学具有重要意义,因为其中涉及的关键分子过程高度保持不变。时至今日,大肠杆菌仍备受关注,一方面是因为它是一种重要的模式生物,另一方面也是因为了解影响复制保真度的因素可能对抗生素耐药性的产生具有重要意义。重要的是,高分辨率单分子和活细胞成像、全基因组测序以及低温电子显微镜技术在过去十年中得到了广泛应用,这使我们能够重新审视关于复制体的某些假设,并对它们的工作原理有了非常详细的了解。对于复制体的许多部分,我们已经重建了其逐步运行的机制,并发现了一些新的参与者。本综述总结了这一领域的最新进展,重点关注:(a) 复制体的结构及其各组成部分的作用机制;(b) 复制体交易和修复的组织;(c) 复制体的动态;(d) 影响 DNA 合成的碱基和糖保真度的因素。
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引用次数: 0
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
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