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Different outer membrane c-type cytochromes are involved in direct interspecies electron transfer to Geobacter or Methanosarcina species. 不同的外膜 c 型细胞色素参与了与 Geobacter 或 Methanosarcina 物种之间的直接种间电子传递。
Pub Date : 2022-09-23 eCollection Date: 2022-09-01 DOI: 10.1002/mlf2.12037
Dawn E Holmes, Jinjie Zhou, Jessica A Smith, Caiqin Wang, Xinying Liu, Derek R Lovley

Direct interspecies electron transfer (DIET) may be most important in methanogenic environments, but mechanistic studies of DIET to date have primarily focused on cocultures in which fumarate was the terminal electron acceptor. To better understand DIET with methanogens, the transcriptome of Geobacter metallireducens during DIET-based growth with G. sulfurreducens reducing fumarate was compared with G. metallireducens grown in coculture with diverse Methanosarcina. The transcriptome of G. metallireducens cocultured with G. sulfurreducens was significantly different from those with Methanosarcina. Furthermore, the transcriptome of G. metallireducens grown with Methanosarcina barkeri, which lacks outer-surface c-type cytochromes, differed from those of G. metallireducens cocultured with M. acetivorans or M. subterranea, which have an outer-surface c-type cytochrome that serves as an electrical connect for DIET. Differences in G. metallireducens expression patterns for genes involved in extracellular electron transfer were particularly notable. Cocultures with c-type cytochrome deletion mutant strains, ∆Gmet_0930, ∆Gmet_0557 and ∆Gmet_2896, never became established with G. sulfurreducens but adapted to grow with all three Methanosarcina. Two porin-cytochrome complexes, PccF and PccG, were important for DIET; however, PccG was more important for growth with Methanosarcina. Unlike cocultures with G. sulfurreducens and M. acetivorans, electrically conductive pili were not needed for growth with M. barkeri. Shewanella oneidensis, another electroactive microbe with abundant outer-surface c-type cytochromes, did not grow via DIET. The results demonstrate that the presence of outer-surface c-type cytochromes does not necessarily confer the capacity for DIET and emphasize the impact of the electron-accepting partner on the physiology of the electron-donating DIET partner.

种间直接电子传递(DIET)在产甲烷环境中可能最为重要,但迄今为止对 DIET 的机理研究主要集中在以富马酸盐为终端电子受体的共培养物中。为了更好地了解甲烷菌的 DIET,研究人员比较了在 DIET 基础上与还原富马酸的 G. sulfurreducens 共同生长的 Geobacter metallireducens 和与不同的 Methanosarcina 共同生长的 Geobacter metallireducens 的转录组。与 G. sulfurreducens 共培养的 G. metallireducens 的转录组明显不同于与 Methanosarcina 共培养的 G. metallireducens。此外,与缺乏外表面 c 型细胞色素的 Methanosarcina barkeri 共同培养的 G. metallireducens 的转录组与与 M. acetivorans 或 M. subterranea 共同培养的 G. metallireducens 的转录组不同,后者具有外表面 c 型细胞色素,可作为 DIET 的电连接。参与细胞外电子传递的基因在 G. metallireducens 中的表达模式差异尤其明显。与 c 型细胞色素缺失突变株 ∆Gmet_0930、∆Gmet_0557 和 ∆Gmet_2896 的共培养从未与 G. sulfurreducens 建立起来,但却适应了与所有三种 Methanosarcina 的生长。两种孔蛋白-细胞色素复合物(PccF 和 PccG)对 DIET 很重要;但 PccG 对与 Methanosarcina 的生长更为重要。与 G. sulfurreducens 和 M. acetivorans 的共培养不同,与 M. barkeri 的生长不需要导电纤毛。Shewanella oneidensis 是另一种电活性微生物,具有丰富的外表面 c 型细胞色素,但没有通过 DIET 生长。这些结果表明,外表面 c 型细胞色素的存在并不一定赋予 DIET 的能力,并强调了接受电子的伙伴对提供电子的 DIET 伙伴的生理机能的影响。
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引用次数: 0
A deep-sea sulfate-reducing bacterium generates zero-valent sulfur via metabolizing thiosulfate. 一种深海硫酸盐还原菌通过代谢硫代硫酸盐产生零价硫。
Pub Date : 2022-09-23 eCollection Date: 2022-09-01 DOI: 10.1002/mlf2.12038
Rui Liu, Yeqi Shan, Shichuan Xi, Xin Zhang, Chaomin Sun

Zero-valent sulfur (ZVS) is a crucial intermediate in the sulfur geobiochemical circulation and is widespread in deep-sea cold seeps. Sulfur-oxidizing bacteria are thought to be the major contributors to the formation of ZVS. However, ZVS production mediated by sulfate-reducing bacteria (SRB) has rarely been reported. In this study, we isolated and cultured a typical SRB designated Oceanidesulfovibrio marinus CS1 from deep-sea cold seep sediment in the South China Sea. We show that O. marinus CS1 forms ZVS in the medium supplemented with thiosulfate. Proteomic and protein activity assays revealed that thiosulfate reductase (PhsA) and the sulfide:quinone oxidoreductase (SQR) played key roles in driving ZVS formation in O. marinus CS1. During this process, thiosulfate firstly was reduced by PhsA to form sulfide, then sulfide was oxidized by SQR to produce ZVS. The expressions of PhsA and SQR were significantly upregulated when O. marinus CS1 was cultured in a deep-sea cold seep, strongly indicating that strain CS1 might form ZVS in the deep-sea environment. Notably, homologs of phsA and sqr were widely identified from microbes living in sediments of deep-sea cold seep in the South China Sea by the metagenomic analysis. We thus propose that SRB containing phsA and sqr genes potentially contribute to the formation of ZVS in deep-sea cold seep environments.

零价硫(ZVS)是硫地球生物化学循环中的一个重要中间体,广泛存在于深海冷渗漏中。硫氧化细菌被认为是形成 ZVS 的主要因素。然而,由硫酸盐还原菌(SRB)介导的 ZVS 生成却鲜有报道。在本研究中,我们从中国南海的深海冷渗漏沉积物中分离并培养了一种典型的 SRB,命名为海洋硫弧菌 CS1。我们发现,O. marinus CS1 在添加了硫代硫酸钠的培养基中会形成 ZVS。蛋白质组和蛋白质活性分析表明,硫代硫酸盐还原酶(PhsA)和硫化物:醌氧化还原酶(SQR)在O. marinus CS1形成ZVS的过程中发挥了关键作用。在此过程中,硫代硫酸盐首先被 PhsA 还原成硫化物,然后硫化物被 SQR 氧化生成 ZVS。在深海冷渗漏中培养 O. marinus CS1 时,PhsA 和 SQR 的表达明显上调,这有力地表明 CS1 菌株可能在深海环境中形成 ZVS。值得注意的是,通过元基因组分析,我们从生活在中国南海深海冷渗漏沉积物中的微生物中广泛发现了 phsA 和 sqr 的同源物。因此,我们认为含有 phsA 和 sqr 基因的 SRB 有可能有助于深海冷渗漏环境中 ZVS 的形成。
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引用次数: 0
Assessing global fungal threats to humans. 评估全球真菌对人类的威胁。
Pub Date : 2022-09-22 eCollection Date: 2022-09-01 DOI: 10.1002/mlf2.12036
Jianping Xu

Fungi are an integral part of the earth's biosphere. They are broadly distributed in all continents and ecosystems and play a diversity of roles. Here, I review our current understanding of fungal threats to humans and describe the major factors that contribute to various threats. Among the 140,000 or so known species out of the estimated six million fungal species on Earth, about 10% directly or indirectly threaten human health and welfare. Major threats include mushroom poisoning, fungal allergies, infections of crop plants, food contamination by mycotoxins, and mycoses in humans. A growing number of factors have been identified to impact various fungal threats, including human demographics, crop distributions, anthropogenic activities, pathogen dispersals, global climate change, and/or the applications of antifungal drugs and agricultural fungicides. However, while models have been developed for analyzing various processes of individual threats and threat managements, current data are primarily descriptive and incomplete, and there are significant obstacles to integration of the diverse factors into accurate quantitative assessments of fungal threats. With increasing technological advances and concerted efforts to track the spatial and temporal data on climate and environmental variables; mycotoxins in the feed and food supply chains; fungal population dynamics in crop fields, human and animal populations, and the environment; human population demographics; and the prevalence and severities of fungal allergies and diseases, our ability to accurately assess fungal threats will improve. Such improvements should help us develop holistic strategies to manage fungal threats in the future.

真菌是地球生物圈不可分割的一部分。它们广泛分布于各大洲和生态系统中,发挥着多种多样的作用。在此,我将回顾我们目前对真菌对人类威胁的认识,并描述造成各种威胁的主要因素。据估计,地球上有 600 万种真菌,在 14 万种左右的已知真菌中,约有 10% 直接或间接威胁着人类的健康和福祉。主要威胁包括蘑菇中毒、真菌过敏、农作物感染、真菌毒素污染食物以及人类真菌病。影响各种真菌威胁的因素越来越多,包括人类人口统计、作物分布、人为活动、病原体扩散、全球气候变化和/或抗真菌药物和农用杀真菌剂的应用。然而,虽然已经开发出了用于分析各种威胁和威胁管理过程的模型,但目前的数据主要是描述性的,并不完整,而且在将各种因素整合到对真菌威胁的精确定量评估中时,还存在很大的障碍。随着技术的不断进步,以及对气候和环境变量、饲料和食品供应链中的霉菌毒素、作物田、人类和动物种群以及环境中的真菌种群动态、人类人口统计、真菌过敏症和疾病的流行率和严重程度等时空数据进行追踪的共同努力,我们准确评估真菌威胁的能力将会得到提高。这些改进将有助于我们制定整体战略来管理未来的真菌威胁。
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引用次数: 0
Climate warming restructures seasonal dynamics of grassland soil microbial communities. 气候变暖重构草地土壤微生物群落的季节动态。
Pub Date : 2022-09-15 eCollection Date: 2022-09-01 DOI: 10.1002/mlf2.12035
Xue Guo, Mengting Yuan, Jiesi Lei, Zhou Shi, Xishu Zhou, Jiabao Li, Ye Deng, Yunfeng Yang, Liyou Wu, Yiqi Luo, James M Tiedje, Jizhong Zhou

Soil microbial community's responses to climate warming alter the global carbon cycle. In temperate ecosystems, soil microbial communities function along seasonal cycles. However, little is known about how the responses of soil microbial communities to warming vary when the season changes. In this study, we investigated the seasonal dynamics of soil bacterial community under experimental warming in a temperate tall-grass prairie ecosystem. Our results showed that warming significantly (p = 0.001) shifted community structure, such that the differences of microbial communities between warming and control plots increased nonlinearly (R 2 = 0.578, p = 0.021) from spring to winter. Also, warming significantly (p < 0.050) increased microbial network complexity and robustness, especially during the colder seasons, despite large variations in network size and complexity in different seasons. In addition, the relative importance of stochastic processes in shaping the microbial community decreased by warming in fall and winter but not in spring and summer. Our study indicates that climate warming restructures the seasonal dynamics of soil microbial community in a temperate ecosystem. Such seasonality of microbial responses to warming may enlarge over time and could have significant impacts on the terrestrial carbon cycle.

土壤微生物群落对气候变暖的反应改变了全球碳循环。在温带生态系统中,土壤微生物群落按季节周期发挥作用。然而,人们对季节变化时土壤微生物群落对气候变暖的响应如何变化知之甚少。在这项研究中,我们调查了温带高草草原生态系统在实验性变暖条件下土壤细菌群落的季节动态。结果表明,气候变暖明显(p = 0.001)改变了群落结构,从春季到冬季,气候变暖地块与对照地块之间的微生物群落差异呈非线性增长(R 2 = 0.578,p = 0.021)。同时,气候变暖也明显(p
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引用次数: 0
Massive-scale genomic analysis reveals SARS-CoV-2 mutation characteristics and evolutionary trends. 大规模基因组分析揭示了严重急性呼吸系统综合征冠状病毒2型的突变特征和进化趋势。
Pub Date : 2022-09-01 Epub Date: 2022-09-26 DOI: 10.1002/mlf2.12040
Yamin Sun, Min Wang, Wenchao Lin, Wei Dong, Jianguo Xu

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in significant societal costs. Hence, an in-depth understanding of SARS-CoV-2 virus mutation and its evolution will help determine the direction of the COVID-19 pandemic. In this study, we identified 296,728 de novo mutations in more than 2,800,000 high-quality SARS-CoV-2 genomes. All possible factors affecting the mutation frequency of SARS-CoV-2 in human hosts were analyzed, including zinc finger antiviral proteins, sequence context, amino acid change, and translation efficiency. As a result, we proposed that when adenine (A) and tyrosine (T) bases are in the context of AM (M stands for adenine or cytosine) or TA motif, A or T base has lower mutation frequency. Furthermore, we hypothesized that translation efficiency can affect the mutation frequency of the third position of the codon by the selection, which explains why SARS-CoV-2 prefers AT3 codons usage. In addition, we found a host-specific asymmetric dinucleotide mutation frequency in the SARS-CoV-2 genome, which provides a new basis for determining the origin of the SARS-CoV-2. Finally, we summarize all possible factors affecting mutation frequency and provide insights into the mutation characteristics and evolutionary trends of SARS-CoV-2.

严重急性呼吸系统综合征冠状病毒2型大流行造成了巨大的社会成本。因此,深入了解SARS-CoV-2病毒变异及其进化将有助于确定新冠肺炎大流行的方向。在这项研究中,我们在超过2800000个高质量的严重急性呼吸系统综合征冠状病毒2型基因组中鉴定了296728个新突变。分析了影响严重急性呼吸系统综合征冠状病毒2型在人类宿主中突变频率的所有可能因素,包括锌指抗病毒蛋白、序列背景、氨基酸变化和翻译效率。因此,我们提出当腺嘌呤(a)和酪氨酸(T)碱基在AM(M代表腺嘌呤或胞嘧啶)或TA基序的上下文中时,a或T碱基具有较低的突变频率。此外,我们假设翻译效率可以通过选择影响密码子第三位的突变频率,这解释了为什么严重急性呼吸系统综合征冠状病毒2型更喜欢使用AT3密码子。此外,我们在严重急性呼吸系统综合征冠状病毒2型基因组中发现了一种宿主特异性不对称二核苷酸突变频率,这为确定严重急性呼吸系冠状病毒2型的起源提供了新的依据。最后,我们总结了影响突变频率的所有可能因素,并深入了解了严重急性呼吸系统综合征冠状病毒2型的突变特征和进化趋势。
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引用次数: 0
Maternal and neonatal viromes indicate the risk of offspring's gastrointestinal tract exposure to pathogenic viruses of vaginal origin during delivery. 母体和新生儿病毒群表明,在分娩过程中,后代的胃肠道有可能接触到来自阴道的致病病毒。
Pub Date : 2022-08-25 eCollection Date: 2022-09-01 DOI: 10.1002/mlf2.12034
Jinfeng Wang, Liwen Xiao, Baichuan Xiao, Bing Zhang, Zhenqiang Zuo, Peifeng Ji, Jiayong Zheng, Xiaoqing Li, Fangqing Zhao

A cumulative effect of enterovirus and gluten intake on the risk of celiac disease autoimmunity in infants highlights the significance of viral exposure in early life on the health of children. However, pathogenic viruses may be transmitted to the offspring in an earlier period, raising the possibility that women whose vaginas are inhabited by such viruses may have had their babies infected as early as the time of delivery. A high-resolution intergenerational virome atlas was obtained by metagenomic sequencing and virome analysis on 486 samples from six body sites of 99 mother-neonate pairs. We found that neonates had less diverse oral and enteric viruses than mothers. Vaginally delivered newborns seconds after birth had a more similar oral virome and more viruses of vaginal origin than cesarean-section (C-section) newborns (56.9% vs. 5.8%). Such viruses include both Lactobacillus phage and potentially pathogenic viruses, such as herpesvirus, vaccinia virus, and hepacivirus, illustrating a relatively high variety of the pioneer viral taxa at the time of delivery and a delivery-dependent mother-to-neonate transmission along the vaginal-oral-intestinal route. Neonates are exposed to vaginal viruses as they pass through the reproductive tract, and viruses of vaginal origin may threaten their health. These findings challenge the conventional notion that vaginal delivery is definitely better than cesarean delivery from the perspective of microbial transmission. Screening for vaginal virome before delivery is a worthwhile step to advocate in normal labor to eliminate the risk of intergenerational transmission of pathogenic viruses to offspring.

肠道病毒和麸质摄入量对婴儿乳糜泻自身免疫风险的累积效应凸显了生命早期病毒暴露对儿童健康的重要影响。然而,致病性病毒可能会在更早的时期传播给后代,这就提出了一种可能性,即阴道中栖息有此类病毒的妇女可能早在分娩时就已使其婴儿受到感染。通过对来自 99 对母婴的 6 个身体部位的 486 个样本进行元基因组测序和病毒组分析,我们获得了高分辨率的代际病毒组图谱。我们发现,新生儿口腔和肠道病毒的多样性低于母亲。与剖腹产新生儿(56.9% 对 5.8%)相比,经阴道分娩的新生儿在出生后几秒钟内的口腔病毒组更为相似,且有更多来自阴道的病毒。这些病毒包括乳酸杆菌噬菌体和潜在的致病性病毒,如疱疹病毒、疫苗病毒和肝细胞病毒,说明分娩时先驱病毒类群的种类相对较多,并说明母婴传播沿阴道-口腔-肠道途径依赖于分娩。新生儿在通过生殖道时会接触到阴道病毒,而来自阴道的病毒可能会威胁新生儿的健康。这些发现对 "从微生物传播的角度来看,阴道分娩肯定优于剖宫产 "的传统观念提出了质疑。在顺产中提倡在分娩前筛查阴道病毒群,以消除病原体病毒代际传播给后代的风险,这是一个值得提倡的步骤。
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引用次数: 0
A novel Methylomirabilota methanotroph potentially couples methane oxidation to iodate reduction. 一种新型甲烷养甲虫有可能将甲烷氧化与碘酸盐还原结合起来。
Pub Date : 2022-08-09 eCollection Date: 2022-09-01 DOI: 10.1002/mlf2.12033
Baoli Zhu, Clemens Karwautz, Stefan Andrei, Andreas Klingl, Jakob Pernthaler, Tillmann Lueders

Methane oxidizing microbes play a key role in reducing the emission of this potent greenhouse gas to the atmosphere. The known versatility of the recently discovered anaerobic Methylomirabilota methanotrophs is limited. Here, we report a novel uncultured Methylomirabilis species, Candidatus Methylomirabilis iodofontis, with the genetic potential of iodate respiration from biofilm in iodine-rich cavern spring water. Star-like cells resembling Methylomirabilis oxyfera were directly observed from the biofilm and a high-quality metagenome-assembled genome (MAG) of Ca. M. iodofontis was assembled. In addition to oxygenic denitrification and aerobic methane oxidation pathways, the M. iodofontis MAG also indicated its iodate-reducing potential, a capability that would enable the bacterium to use iodate other than nitrite as an electron acceptor, a hitherto unrecognized metabolic potential of Methylomirabilota methanotrophs. The results advance the current understanding of the ecophysiology of anaerobic Methylomirabilota methanotrophs and may suggest an additional methane sink, especially in iodate-rich ecosystems.

甲烷氧化微生物在减少这种强效温室气体向大气排放方面发挥着关键作用。最近发现的厌氧型甲烷滋养微生物的多功能性是有限的。在这里,我们报告了一种新的未培养的甲氧甲烷菌--Candidatus Methylomirabilis iodofontis,它具有从富含碘的岩洞泉水生物膜中进行碘酸盐呼吸的遗传潜力。从生物膜中直接观察到了类似于Methylomirabilis oxyfera的星状细胞,并获得了Ca.M. iodofontis的高质量元基因组(MAG)。M. iodofontis 的高质量元基因组(MAG)。除了含氧反硝化和需氧甲烷氧化途径外,M. iodofontis 的 MAG 还显示了其碘酸盐还原潜力,这种能力使该细菌能够使用亚硝酸盐以外的碘酸盐作为电子受体,这是迄今为止尚未认识到的 Methylomirabilota 甲烷营养菌的代谢潜力。这些结果加深了人们目前对厌氧甲烷菌生态生理学的了解,并可能为甲烷的吸收提供了新的途径,尤其是在富含碘酸盐的生态系统中。
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引用次数: 0
Unveiling degradation mechanism of PAHs by a Sphingobium strain from a microbial consortium. 揭示微生物联合体中一株鞘氨醇菌株降解多环芳烃的机制。
Pub Date : 2022-07-25 eCollection Date: 2022-09-01 DOI: 10.1002/mlf2.12032
Lige Zhang, Huan Liu, Junbiao Dai, Ping Xu, Hongzhi Tang

Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent pollutants with adverse biological effects and pose a serious threat to ecological environments and human health. The previously isolated phenanthrene-degrading bacterial consortium (PDMC) consists of the genera Sphingobium and Pseudomonas and can degrade a wide range of PAHs. To identify the degradation mechanism of PAHs in the consortium PDMC, metagenomic binning was conducted and a Sphingomonadales assembly genome with 100% completeness was obtained. Additionally, Sphingobium sp. SHPJ-2, an efficient degrader of PAHs, was successfully isolated from the consortium PDMC. Strain SHPJ-2 has powerful degrading abilities and various degradation pathways of high-molecular-weight PAHs, including fluoranthene, pyrene, benzo[a]anthracene, and chrysene. Two ring-hydroxylating dioxygenases, five cytochrome P450s, and a pair of electron transfer chains associated with PAH degradation in strain SHPJ-2, which share 83.0%-99.0% similarity with their corresponding homologous proteins, were identified by a combination of Sphingomonadales assembly genome annotation, reverse-transcription quantitative polymerase chain reaction and heterologous expression. Furthermore, when coexpressed in Escherichia coli BL21(DE3) with the appropriate electron transfer chain, PhnA1B1 could effectively degrade chrysene and benzo[a]anthracene, while PhnA2B2 degrade fluoranthene. Altogether, these results provide a comprehensive assessment of strain SHPJ-2 and contribute to a better understanding of the molecular mechanism responsible for the PAH degradation.

多环芳烃(PAHs)是一类具有不良生物效应的持久性污染物,对生态环境和人类健康构成严重威胁。之前分离出的菲类降解细菌群(PDMC)由鞘氨醇属和假单胞菌属组成,可降解多种 PAHs。为了确定多环芳烃在联合体 PDMC 中的降解机制,研究人员进行了元基因组分选,并获得了完整度为 100% 的 Sphingomonadales 组合基因组。此外,还成功地从 PDMC 菌群中分离出了多环芳烃的高效降解菌株 Sphingobium sp.菌株 SHPJ-2 对高分子量 PAHs(包括荧蒽、芘、苯并[a]蒽和菊烯)具有强大的降解能力和多种降解途径。通过鞘氨醇单胞菌组装基因组注释、反转录定量聚合酶链反应和异源表达相结合的方法,鉴定出了与多环芳烃降解相关的两种环羟化二氧酶、五种细胞色素 P450 和一对电子传递链,它们与相应的同源蛋白的相似度在 83.0%-99.0% 之间。此外,当 PhnA1B1 与相应的电子传递链在大肠杆菌 BL21(DE3) 中共表达时,能有效降解菊烯和苯并[a]蒽,而 PhnA2B2 则能降解荧蒽。总之,这些结果提供了对SHPJ-2菌株的全面评估,有助于更好地理解多环芳烃降解的分子机制。
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引用次数: 0
Bacillus subtilis produces (p)ppGpp in response to the bacteriostatic antibiotic chloramphenicol to prevent its potential bactericidal effect. 枯草芽孢杆菌对抑菌抗生素氯霉素产生 (p)ppGpp 反应,以防止其潜在的杀菌作用。
Pub Date : 2022-06-30 eCollection Date: 2022-06-01 DOI: 10.1002/mlf2.12031
Jin Yang, Jessica T Barra, Danny K Fung, Jue D Wang

Antibiotics combat bacteria through their bacteriostatic (by growth inhibition) or bactericidal (by killing bacteria) action. Mechanistically, it has been proposed that bactericidal antibiotics trigger cellular damage, while bacteriostatic antibiotics suppress cellular metabolism. Here, we demonstrate how the difference between bacteriostatic and bactericidal activities of the antibiotic chloramphenicol can be attributed to an antibiotic-induced bacterial protective response: the stringent response. Chloramphenicol targets the ribosome to inhibit the growth of the Gram-positive bacterium Bacillus subtilis. Intriguingly, we found that chloramphenicol becomes bactericidal in B. subtilis mutants unable to produce (p)ppGpp. We observed a similar (p)ppGpp-dependent bactericidal effect of chloramphenicol in the Gram-positive pathogen Enterococcus faecalis. In B. subtilis, chloramphenicol treatment induces (p)ppGpp accumulation through the action of the (p)ppGpp synthetase RelA. (p)ppGpp subsequently depletes the intracellular concentration of GTP and antagonizes GTP action. This GTP regulation is critical for preventing chloramphenicol from killing B. subtilis, as bypassing (p)ppGpp-dependent GTP regulation potentiates chloramphenicol killing, while reducing GTP synthesis increases survival. Finally, chloramphenicol treatment protects cells from the classical bactericidal antibiotic vancomycin, reminiscent of the clinical phenomenon of antibiotic antagonism. Taken together, our findings suggest a role of (p)ppGpp in the control of the bacteriostatic and bactericidal activity of antibiotics in Gram-positive bacteria, which can be exploited to potentiate the efficacy of existing antibiotics.

抗生素通过抑菌(抑制生长)或杀菌(杀死细菌)作用来对付细菌。从机理上讲,有人认为杀菌型抗生素会引发细胞损伤,而抑菌型抗生素则会抑制细胞代谢。在这里,我们证明了抗生素氯霉素的抑菌和杀菌活性之间的差异可归因于抗生素诱导的细菌保护反应:严格反应。氯霉素以核糖体为目标,抑制革兰氏阳性细菌枯草杆菌的生长。有趣的是,我们发现氯霉素在不能产生 (p)ppGpp 的枯草杆菌突变体中具有杀菌作用。我们在革兰氏阳性病原体粪肠球菌(Enterococcus faecalis)中也观察到了类似的(pp)ppGpp 依赖性氯霉素杀菌作用。在枯草杆菌中,氯霉素通过(pp)ppGpp 合成酶 RelA 的作用诱导(pp)ppGpp 的积累,随后(pp)ppGpp 会消耗细胞内 GTP 的浓度并拮抗 GTP 的作用。这种 GTP 调节对于防止氯霉素杀死枯草杆菌至关重要,因为绕过(pp)ppGpp 依赖性 GTP 调节会增强氯霉素的杀伤力,而减少 GTP 合成则会提高存活率。最后,氯霉素处理可保护细胞免受经典杀菌抗生素万古霉素的伤害,这让人联想到临床上的抗生素拮抗现象。综上所述,我们的研究结果表明,(p)ppGpp 在控制革兰氏阳性细菌中抗生素的抑菌和杀菌活性方面发挥着作用,可以利用它来增强现有抗生素的功效。
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引用次数: 0
Substrate availability and toxicity shape the structure of microbial communities engaged in metabolic division of labor. 底物的可用性和毒性决定了参与代谢分工的微生物群落的结构。
Pub Date : 2022-06-30 eCollection Date: 2022-06-01 DOI: 10.1002/mlf2.12025
Miaoxiao Wang, Xiaoli Chen, Yue-Qin Tang, Yong Nie, Xiao-Lei Wu

Metabolic division of labor (MDOL) represents a widespread natural phenomenon, whereby a complex metabolic pathway is shared between different strains within a community in a mutually beneficial manner. However, little is known about how the composition of such a microbial community is regulated. We hypothesized that when degradation of an organic compound is carried out via MDOL, the concentration and toxicity of the substrate modulate the benefit allocation between the two microbial populations, thus affecting the structure of this community. We tested this hypothesis by combining modeling with experiments using a synthetic consortium. Our modeling analysis suggests that the proportion of the population executing the first metabolic step can be simply estimated by Monod-like formulas governed by substrate concentration and toxicity. Our model and the proposed formula were able to quantitatively predict the structure of our synthetic consortium. Further analysis demonstrates that our rule is also applicable in estimating community structures in spatially structured environments. Together, our work clearly demonstrates that the structure of MDOL communities can be quantitatively predicted using available information on environmental factors, thus providing novel insights into how to manage artificial microbial systems for the wide application of the bioindustry.

代谢分工(MDOL)是一种普遍存在的自然现象,即群落中的不同菌株以互利的方式共享复杂的代谢途径。然而,人们对这种微生物群落的组成是如何调节的知之甚少。我们假设,当通过 MDOL 降解有机化合物时,底物的浓度和毒性会调节两个微生物种群之间的利益分配,从而影响该群落的结构。我们利用合成联合体将建模与实验相结合,对这一假设进行了验证。我们的建模分析表明,执行第一个代谢步骤的种群比例可以通过受底物浓度和毒性制约的类似莫诺公式进行简单估算。我们的模型和提出的公式能够定量预测合成联合体的结构。进一步的分析表明,我们的规则也适用于估算空间结构环境中的群落结构。总之,我们的工作清楚地表明,MDOL 群落的结构可以利用现有的环境因素信息进行定量预测,从而为如何管理人工微生物系统以广泛应用于生物产业提供了新的见解。
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引用次数: 0
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