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Microbial hub signaling compounds: natural products disproportionally shape microbiome composition and structure. 微生物中枢信号化合物:天然产品不成比例地塑造了微生物组的组成和结构。
Pub Date : 2024-09-14 eCollection Date: 2024-01-01 DOI: 10.1093/femsml/uqae017
Axel A Brakhage

Microbiomes are shaped by abiotic factors like nutrients, oxygen availability, pH, temperature, and so on, but also by biotic factors including low molecular weight organic compounds referred to as natural products (NPs). Based on genome analyses, millions of these compounds are predicted to exist in nature, some of them have found important applications e.g. as antibiotics. Based on recent data I propose a model that some of these compounds function as microbial hub signaling compounds, i.e. they have a higher hierarchical influence on microbiomes. These compounds have direct effects e.g. by inhibiting microorganisms and thereby exclude them from a microbiome (excluded). Some microorganisms do not respond at all (nonresponder), others respond by producing themselves NPs like a second wave of information molecules (message responder) influencing other microorganisms, but conceivably a more limited spectrum. Some microorganisms may respond to the hub compounds with their chemical modification (message modifiers). This way, the modified NPs may have themselves signaling function for a subset of microorganisms. Finally, it is also likely that NPs act as food source (C- and/or N-source) for microorganisms specialized on their degradation. As a consequence, such specialized microorganisms are selectively recruited to the microbiota.

微生物组不仅受非生物因素(如营养、氧气供应、pH 值、温度等)的影响,还受生物因素(包括被称为天然产物(NPs)的低分子量有机化合物)的影响。根据基因组分析预测,自然界中存在数以百万计的此类化合物,其中一些已被用作抗生素等重要用途。根据最近的数据,我提出了一个模型,其中一些化合物具有微生物中枢信号化合物的功能,即它们对微生物群具有更高层次的影响。这些化合物具有直接影响,例如抑制微生物,从而将它们排除在微生物群之外(排除)。有些微生物根本不做出反应(无反应者),有些微生物则通过产生自身的 NPs 做出反应,就像第二波信息分子(信息反应者)影响其他微生物,但可以想象的是,影响的范围更加有限。有些微生物可能会通过化学修饰(信息修饰)对中枢化合物做出反应。这样,经过修饰的 NP 本身可能对一部分微生物具有信号功能。最后,NPs 还可能成为专门降解 NPs 的微生物的食物来源(C-和/或 N-来源)。因此,这类专门微生物会被有选择地招募到微生物群中。
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引用次数: 0
Microbial markets: socio-economic perspective in studying microbial communities. 微生物市场:从社会经济角度研究微生物群落。
Pub Date : 2024-08-28 eCollection Date: 2024-01-01 DOI: 10.1093/femsml/uqae016
Fariha Mostafa, Aileen Krüger, Tim Nies, Julia Frunzke, Kerstin Schipper, Anna Matuszyńska

Studying microbial communities through a socio-economic lens, this paper draws parallels with human economic transactions and microbes' race for resources. Extending the 'Market Economy' concept of social science to microbial ecosystems, the paper aims to contribute to comprehending the collaborative and competitive dynamics among microorganisms. Created by a multidisciplinary team of an economist, microbiologists, and mathematicians, the paper also highlights the risks involved in employing a socio-economic perspective to explain the complexities of natural ecosystems. Navigating through microbial markets offers insights into the implications of these interactions while emphasizing the need for cautious interpretation within the broader ecological context. We hope that this paper will be a fruitful source of inspiration for future studies on microbial communities.

本文通过社会经济视角研究微生物群落,将人类的经济交易与微生物对资源的争夺相提并论。本文将社会科学中的 "市场经济 "概念扩展到微生物生态系统,旨在帮助理解微生物之间的合作与竞争动态。该论文由经济学家、微生物学家和数学家组成的多学科团队撰写,同时也强调了采用社会经济视角来解释复杂的自然生态系统所涉及的风险。通过微生物市场的导航,我们可以深入了解这些相互作用的影响,同时也强调了在更广泛的生态背景下谨慎解释的必要性。我们希望本文能为今后的微生物群落研究提供丰富的灵感。
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引用次数: 0
Resistance against aminoglycoside antibiotics via drug or target modification enables community-wide antiphage defense. 通过药物或靶点修饰对氨基糖苷类抗生素的抗性可实现全群落的抗虹吸防御。
Pub Date : 2024-08-15 eCollection Date: 2024-01-01 DOI: 10.1093/femsml/uqae015
Larissa Kever, Qian Zhang, Aël Hardy, Philipp Westhoff, Yi Yu, Julia Frunzke

The ongoing arms race between bacteria and phages has forced bacteria to evolve a sophisticated set of antiphage defense mechanisms that constitute the bacterial immune system. In our previous study, we highlighted the antiphage properties of aminoglycoside antibiotics, which are naturally secreted by Streptomyces. Successful inhibition of phage infection was achieved by addition of pure compounds and supernatants from a natural producer strain emphasizing the potential for community-wide antiphage defense. However, given the dual functionality of these compounds, neighboring bacterial cells require resistance to the antibacterial activity of aminoglycosides to benefit from the protection they confer against phages. In this study, we tested a variety of different aminoglycoside resistance mechanisms acting via drug or target (16S rRNA) modification and demonstrated that they do not interfere with the antiphage properties of the molecules. Furthermore, we confirmed the antiphage impact of aminoglycosides in a community context by coculturing phage-susceptible, apramycin-resistant Streptomyces venezuelae with the apramycin-producing strain Streptoalloteichus tenebrarius. Given the prevalence of aminoglycoside resistance among natural bacterial isolates, this study highlights the ecological relevance of chemical defense via aminoglycosides at the community level.

细菌与噬菌体之间持续不断的军备竞赛迫使细菌进化出一套复杂的抗噬菌体防御机制,这套机制构成了细菌免疫系统。在之前的研究中,我们强调了由链霉菌天然分泌的氨基糖苷类抗生素的抗噬菌体特性。通过添加来自天然生产菌株的纯化合物和上清液,我们成功地抑制了噬菌体的感染,强调了全群落抗噬菌体防御的潜力。然而,鉴于这些化合物的双重功能,邻近的细菌细胞需要对氨基糖苷类化合物的抗菌活性产生抗性,才能从它们对噬菌体的保护中获益。在这项研究中,我们测试了通过药物或靶标(16S rRNA)修饰作用的各种不同的氨基糖苷类抗性机制,结果表明它们不会干扰分子的抗噬菌体特性。此外,我们还通过将对噬菌体敏感、对阿普霉素耐药的委内瑞拉链霉菌与产生阿普霉素的菌株 Streptoalloteichus tenebrarius 进行共培养,证实了氨基糖苷类药物在群落环境中的抗噬菌体作用。鉴于氨基糖苷类药物耐药性在天然细菌分离物中的普遍存在,本研究强调了通过氨基糖苷类药物在群落水平上进行化学防御的生态相关性。
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引用次数: 0
Coordinated regulation of osmotic imbalance by c-di-AMP shapes ß-lactam tolerance in Group B Streptococcus. c-di-AMP 对渗透失衡的协调调节塑造了 B 群链球菌的 ß-内酰胺耐受性。
Pub Date : 2024-06-12 eCollection Date: 2024-01-01 DOI: 10.1093/femsml/uqae014
Terry Brissac, Cécile Guyonnet, Aymane Sadouni, Ariadna Hernández-Montoya, Elise Jacquemet, Rachel Legendre, Odile Sismeiro, Patrick Trieu-Cuot, Philippe Lanotte, Asmaa Tazi, Arnaud Firon

Streptococcus agalactiae is among the few pathogens that have not developed resistance to ß-lactam antibiotics despite decades of clinical use. The molecular basis of this long-lasting susceptibility has not been investigated, and it is not known whether specific mechanisms constrain the emergence of resistance. In this study, we first report ß-lactam tolerance due to the inactivation of the c-di-AMP phosphodiesterase GdpP. Mechanistically, tolerance depends on antagonistic regulation by the repressor BusR, which is activated by c-di-AMP and negatively regulates ß-lactam susceptibility through the BusAB osmolyte transporter and the AmaP/Asp23/GlsB cell envelope stress complex. The BusR transcriptional response is synergistic with the simultaneous allosteric inhibition of potassium and osmolyte transporters by c-di-AMP, which individually contribute to low-level ß-lactam tolerance. Genome-wide transposon mutagenesis confirms the role of GdpP and highlights functional interactions between a lysozyme-like hydrolase, the KhpAB RNA chaperone and the protein S immunomodulator in the response of GBS to ß-lactam. Overall, we demonstrate that c-di-AMP acts as a turgor pressure rheostat, coordinating an integrated response at the transcriptional and post-translational levels to cell wall weakening caused by ß-lactam activity, and reveal additional mechanisms that could foster resistance.

尽管ß-内酰胺类抗生素已在临床上使用了几十年,但在少数病原体中,无乳链球菌还没有对ß-内酰胺类抗生素产生耐药性。这种长期敏感性的分子基础尚未得到研究,也不知道是否有特定的机制限制了耐药性的产生。在这项研究中,我们首次报道了由于 c-di-AMP 磷酸二酯酶 GdpP 失活导致的ß-内酰胺耐药性。从机理上讲,耐受性取决于抑制因子BusR的拮抗调控,BusR被c-di-AMP激活,并通过BusAB渗透转运体和AmaP/Asp23/GlsB细胞包膜应激复合物负向调控ß-内酰胺的敏感性。BusR 的转录反应与 c-di-AMP 同时对钾和渗透溶质转运体的异位抑制具有协同作用,这两种作用都有助于低水平的 ß-内酰胺耐受性。全基因组转座诱变证实了 GdpP 的作用,并强调了溶菌酶样水解酶、KhpAB RNA 合子和蛋白 S 免疫调节剂在 GBS 对ß-内酰胺反应中的功能相互作用。总之,我们证明了c-di-AMP可作为一种抗皱压力调节器,在转录和翻译后水平上协调对ß-内酰胺活性导致的细胞壁削弱的综合反应,并揭示了可促进抗性的其他机制。
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引用次数: 0
Multiple variants of the type VII secretion system in Gram-positive bacteria. 革兰氏阳性细菌 VII 型分泌系统的多种变体。
Pub Date : 2024-06-05 eCollection Date: 2024-01-01 DOI: 10.1093/femsml/uqae013
Stephen R Garrett, Andrew B Higginson, Tracy Palmer

Type VII secretion systems (T7SS) are found in bacteria across the Bacillota and Actinomycetota phyla and have been well described in Staphylococcus aureus, Bacillus subtilis, and pathogenic mycobacteria. The T7SS from Actinomycetota and Bacillota share two common components, a membrane-bound EccC/EssC ATPase and EsxA, a small helical hairpin protein of the WXG100 family. However, they also have additional phylum-specific components, and as a result they are termed the T7SSa (Actinomycetota) and T7SSb (Bacillota), respectively. Here, we identify additional organizations of the T7SS across these two phyla and describe eight additional T7SS subtypes, which we have named T7SSc-T7SSj. T7SSd is found exclusively in Actinomycetota including the Olselnella and Bifodobacterium genus, whereas the other seven are found only in Bacillota. All of the novel subtypes contain the canonical ATPase (TsxC) and the WXG100-family protein (TsxA). Most of them also contain a small ubiquitin-related protein, TsxB, related to the T7SSb EsaB/YukD component. Protein kinases, phosphatases, and forkhead-associated (FHA) proteins are often encoded in the novel T7SS gene clusters. Candidate substrates of these novel T7SS subtypes include LXG-domain and RHS proteins. Predicted substrates are frequently encoded alongside genes for additional small WXG100-related proteins that we speculate serve as cosecretion partners. Collectively our findings reveal unexpected diversity in the T7SS in Gram-positive bacteria.

VII 型分泌系统(T7SS)存在于芽孢杆菌科和放线菌科的细菌中,并在金黄色葡萄球菌、枯草杆菌和致病分枝杆菌中得到了很好的描述。放线菌门和芽孢杆菌门的 T7SS 有两个共同的成分,一个是膜结合的 EccC/EssC ATPase,另一个是 WXG100 家族的小螺旋发夹蛋白 EsxA。不过,它们也有其他门特有的成分,因此分别被称为 T7SSa(放线菌门)和 T7SSb(芽孢杆菌门)。在这里,我们确定了这两个门中 T7SS 的其他组织,并描述了另外 8 种 T7SS 亚型,我们将其命名为 T7SSc-T7SSj。T7SSd 只存在于放线菌门(包括奥氏菌属和双歧杆菌属),而其他七种亚型只存在于芽孢杆菌门(Bacillota)。所有新型亚型都含有标准 ATP 酶(TsxC)和 WXG100 家族蛋白(TsxA)。它们中的大多数还含有一种与泛素有关的小蛋白 TsxB,与 T7SSb EsaB/YukD 成分有关。新型 T7SS 基因簇通常还编码蛋白激酶、磷酸酶和叉头相关蛋白(FHA)。这些新型 T7SS 亚型的候选底物包括 LXG 域蛋白和 RHS 蛋白。预测的底物经常与其他 WXG100 相关小蛋白的基因一起编码,我们推测这些小蛋白是共分泌伙伴。总之,我们的发现揭示了革兰氏阳性菌中 T7SS 意外的多样性。
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引用次数: 0
A cyanobacterial chemotaxis-like system controls phototactic orientation via phosphorylation of two antagonistic response regulators. 蓝藻类趋光性系统通过磷酸化两个拮抗反应调节因子来控制趋光性定向。
Pub Date : 2024-05-27 eCollection Date: 2024-01-01 DOI: 10.1093/femsml/uqae012
Yu Han, Jonas Hammerl, Felicitas E Flemming, Nils Schuergers, Annegret Wilde

Photosynthetic cyanobacteria exhibit phototaxis, utilizing type IV pili (T4P) to navigate either toward or away from a light source. The Tax1 system is a chemotaxis-like signal transduction pathway that controls the switch in cell polarity, which is crucial for positive phototaxis in Synechocystis sp. PCC 6803. The system consists of the blue/green light sensor PixJ, which controls the histidine kinase PixL and two CheY-like response regulators, PixG and PixH. However, the molecular mechanism by which Tax1 regulates T4P activity and polarity is poorly understood. Here, we investigated the phosphotransfer between PixL and its cognate response regulators in vitro and analyzed the localization and function of wild-type and phosphorylation-deficient PixG and PixH during phototaxis. We found that both PixG and PixH are phosphorylated by PixL but have different roles in phototaxis regulation. Only phosphorylated PixG interacts with the T4P motor protein PilB1 and localizes to the leading cell pole under directional light, thereby promoting positive phototaxis. In contrast, PixH is a negative regulator of PixG phosphorylation and inhibits positive phototaxis. We also demonstrated that the C-terminal receiver domain of PixL is essential for positive phototaxis, and modulates the kinase activity of PixL. Our findings reveal the molecular basis of positive phototaxis regulation by the Tax1 system and provide insights into the division of labor between PatA-type and CheY-like response regulators in cyanobacterial chemotaxis-like systems. Furthermore, these findings highlight similarities in the regulation of movement direction during twitching motility in phototactic and chemotactic bacteria.

光合蓝藻具有趋光性,利用 IV 型纤毛虫(T4P)朝向或远离光源。Tax1 系统是一种类似于趋光性的信号转导途径,可控制细胞极性的转换,这对 Synechocystis sp.该系统由控制组氨酸激酶 PixL 的蓝/绿光传感器 PixJ 以及两个类似于 CheY 的反应调节器 PixG 和 PixH 组成。然而,人们对 Tax1 调节 T4P 活性和极性的分子机制知之甚少。在此,我们在体外研究了 PixL 与其同源反应调节因子之间的磷酸转移,并分析了野生型和磷酸化缺陷型 PixG 和 PixH 在趋光过程中的定位和功能。我们发现,PixG 和 PixH 都被 PixL 磷酸化,但在趋光性调控中的作用不同。只有磷酸化的 PixG 能与 T4P 马达蛋白 PilB1 相互作用,并在定向光下定位到前导细胞极,从而促进正光向性。相反,PixH 是 PixG 磷酸化的负调控因子,抑制正光向性。我们还证明了 PixL 的 C 端接收结构域对正光向性至关重要,并能调节 PixL 的激酶活性。我们的研究结果揭示了 Tax1 系统调控正趋光性的分子基础,并深入揭示了蓝藻趋光性类系统中 PatA 型和 CheY 型响应调控因子的分工。此外,这些发现还突显了趋光细菌和趋化细菌在抽动运动过程中运动方向调控的相似性。
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引用次数: 0
Correction to: multireceptor phage cocktail against Salmonella enterica to circumvent phage resistance. 更正:针对肠炎沙门氏菌的多受体噬菌体鸡尾酒,以规避噬菌体抗药性。
Pub Date : 2024-05-22 eCollection Date: 2024-01-01 DOI: 10.1093/femsml/uqae010

[This corrects the article DOI: 10.1093/femsml/uqae003.].

[This corrects the article DOI: 10.1093/femsml/uqae003.].
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引用次数: 0
Time-series metaproteogenomics of a high-CO2 aquifer reveals active viruses with fluctuating abundances and broad host ranges. 高二氧化碳含水层的时间序列元蛋白基因组学揭示了具有波动丰度和广泛宿主范围的活跃病毒。
Pub Date : 2024-05-20 eCollection Date: 2024-01-01 DOI: 10.1093/femsml/uqae011
Carrie Julia Moore, Till L V Bornemann, Perla Abigail Figueroa-Gonzalez, Sarah P Esser, Cristina Moraru, André Rodrigues Soares, Tjorven Hinzke, Anke Trautwein-Schult, Sandra Maaß, Dörte Becher, Joern Starke, Julia Plewka, Lousia Rothe, Alexander J Probst

Ecosystems subject to mantle degassing are of particular interest for understanding global biogeochemistry, as their microbiomes are shaped by prolonged exposure to high CO2 and have recently been suggested to be highly active. While the genetic diversity of bacteria and archaea in these deep biosphere systems have been studied extensively, little is known about how viruses impact these microbial communities. Here, we show that the viral community in a high-CO2 cold-water geyser (Wallender Born, Germany) undergoes substantial fluctuations over a period of 12 days, although the corresponding prokaryotic community remains stable, indicating a newly observed "infect to keep in check" strategy that maintains prokaryotic community structure. We characterized the viral community using metagenomics and metaproteomics, revealing 8 654 viral operational taxonomic units (vOTUs). CRISPR spacer-to-protospacer matching linked 278 vOTUs to 32 hosts, with many vOTUs sharing hosts from different families. High levels of viral structural proteins present in the metaproteome (several structurally annotated based on AlphaFold models) indicate active virion production at the time of sampling. Viral genomes expressed many proteins involved in DNA metabolism and manipulation, and encoded for auxiliary metabolic genes, which likely bolster phosphate and sulfur metabolism of their hosts. The active viral community encodes genes to facilitate acquisition and transformation of host nutrients, and appears to consist of many nutrient-demanding members, based on abundant virion proteins. These findings indicate viruses are inextricably linked to the biogeochemical cycling in this high-CO2 environment and substantially contribute to prokaryotic community stability in the deep biosphere hotspots.

受地幔脱气影响的生态系统对了解全球生物地球化学具有特别的意义,因为它们的微生物群落因长期暴露在高二氧化碳环境中而形成,并且最近被认为是高度活跃的。虽然对这些深层生物圈系统中细菌和古细菌的遗传多样性进行了广泛研究,但对病毒如何影响这些微生物群落却知之甚少。在这里,我们展示了高二氧化碳冷水间歇泉(德国瓦伦德-博恩)中的病毒群落在 12 天内经历了大幅波动,尽管相应的原核生物群落保持稳定,这表明一种新观察到的 "感染控制 "策略能够维持原核生物群落结构。我们利用元基因组学和元蛋白组学描述了病毒群落的特征,发现了 8 654 个病毒操作分类单元(vOTUs)。CRISPR spacer-to-protospacer 匹配将 278 个 vOTUs 与 32 个宿主联系起来,其中许多 vOTUs 共享来自不同家族的宿主。元蛋白组中含有大量病毒结构蛋白(其中几种根据 AlphaFold 模型进行了结构注释),这表明采样时病毒的生产十分活跃。病毒基因组表达了许多参与 DNA 代谢和操作的蛋白质,并为辅助代谢基因编码,这些基因可能会促进宿主的磷酸盐和硫代谢。活跃的病毒群落编码的基因可促进宿主营养物质的获取和转化,根据丰富的病毒蛋白来看,病毒群落似乎由许多需要营养物质的成员组成。这些发现表明,病毒与这一高二氧化碳环境中的生物地球化学循环密不可分,并对深生物圈热点地区原核生物群落的稳定性做出了重大贡献。
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引用次数: 0
Correction to: Multireceptor phage cocktail against Salmonella enterica to circumvent phage resistance 更正:针对肠炎沙门氏菌的多受体噬菌体鸡尾酒可规避噬菌体抗药性
Pub Date : 2024-04-12 DOI: 10.1093/femsml/uqae009
[This corrects the article DOI: 10.1093/femsml/uqae003.].
[This corrects the article DOI: 10.1093/femsml/uqae003.].
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引用次数: 0
Meeting report ‘Microbiology 2023: from single cell to microbiome and host’, an international interacademy conference in Würzburg 会议报告 "微生物学 2023:从单细胞到微生物组和宿主",维尔茨堡国际科学院间会议
Pub Date : 2024-04-05 DOI: 10.1093/femsml/uqae008
Pascale Cossart, Jörg Hacker, David H Holden, Staffan Normark, Jörg Vogel
Abstract On September 20–22 September 2023, the international conference ‘Microbiology 2023: from single cell to microbiome and host’ convened microbiologists from across the globe for a very successful symposium, showcasing cutting-edge research in the field. Invited lecturers delivered exceptional presentations covering a wide range of topics, with a major emphasis on phages and microbiomes, on the relevant bacteria within these ecosystems, and their multifaceted roles in diverse environments. Discussions also spanned the intricate analysis of fundamental bacterial processes, such as cell division, stress resistance, and interactions with phages. Organized by four renowned Academies, the German Leopoldina, the French Académie des sciences, the Royal Society UK, and the Royal Swedish Academy of Sciences, the symposium provided a dynamic platform for experts to share insights and discoveries, leaving participants inspired and eager to integrate new knowledge into their respective projects. The success of Microbiology 2023 prompted the decision to host the next quadrennial academic meeting in Sweden. This choice underscores the commitment to fostering international collaboration and advancing the frontiers of microbiological knowledge. The transition to Sweden promises to be an exciting step in the ongoing global dialogue and specific collaborations on microbiology, a field where researchers will continue to push the boundaries of knowledge, understanding, and innovation not only in health and disease but also in ecology.
摘要 2023 年 9 月 20-22 日,"微生物学 2023:从单细胞到微生物组和宿主 "国际会议召集了来自全球各地的微生物学家,成功举办了一场研讨会,展示了该领域的前沿研究。特邀讲师发表了精彩的演讲,内容涉及广泛的主题,重点是噬菌体和微生物组、这些生态系统中的相关细菌及其在不同环境中的多方面作用。讨论还涉及对细菌基本过程的复杂分析,如细胞分裂、抗压力以及与噬菌体的相互作用。研讨会由德国莱奥波尔迪纳科学院、法国科学院、英国皇家学会和瑞典皇家科学院四所知名科学院主办,为专家们提供了一个分享见解和发现的动态平台,与会者深受启发,渴望将新知识融入各自的项目中。微生物学 2023》的成功促使我们决定在瑞典举办下一届四年一度的学术会议。这一选择强调了促进国际合作和推动微生物知识前沿发展的承诺。在微生物学领域,研究人员将继续推进知识、理解和创新的边界,不仅在健康和疾病领域,而且在生态学领域。
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引用次数: 0
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