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Primary succession of Bifidobacteria drives pathogen resistance in neonatal microbiota assembly 双歧杆菌的初级演替驱动新生儿微生物群的病原体抵抗力
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-06 DOI: 10.1038/s41564-024-01804-9
Yan Shao, Cristina Garcia-Mauriño, Simon Clare, Nicholas J. R. Dawson, Andre Mu, Anne Adoum, Katherine Harcourt, Junyan Liu, Hilary P. Browne, Mark D. Stares, Alison Rodger, Peter Brocklehurst, Nigel Field, Trevor D. Lawley
Human microbiota assembly commences at birth, seeded by both maternal and environmental microorganisms. Ecological theory postulates that primary colonizers dictate microbial community assembly outcomes, yet such microbial priority effects in the human gut remain underexplored. Here using longitudinal faecal metagenomics, we characterized neonatal microbiota assembly for a cohort of 1,288 neonates from the UK. We show that the pioneering neonatal gut microbiota can be stratified into one of three distinct community states, each dominated by a single microbial species and influenced by clinical and host factors, such as maternal age, ethnicity and parity. A community state dominated by Enterococcus faecalis displayed stochastic microbiota assembly with persistent high pathogen loads into infancy. In contrast, community states dominated by Bifidobacterium, specifically B. longum and particularly B. breve, exhibited a stable assembly trajectory and long-term pathogen colonization resistance, probably due to strain-specific functional adaptions to a breast milk-rich neonatal diet. Consistent with our human cohort observation, B. breve demonstrated priority effects and conferred pathogen colonization resistance in a germ-free mouse model. Our findings solidify the crucial role of Bifidobacteria as primary colonizers in shaping the microbiota assembly and functions in early life. Primary colonization by microbial communities dominated by Bifidobacteria contribute to stable gut microbiota assembly and long-term pathogen resistance in neonates.
人类微生物群的形成始于出生时,由母体和环境微生物共同播种。生态学理论推测,初级定植者决定了微生物群落的组合结果,但人类肠道中的这种微生物优先效应仍未得到充分探索。在这里,我们利用纵向粪便元基因组学,对英国 1288 名新生儿的微生物群落组合进行了描述。我们的研究表明,新生儿肠道微生物群可分为三种不同的群落状态,每种状态都由单一微生物物种主导,并受临床和宿主因素(如母亲年龄、种族和胎次)的影响。以粪肠球菌为主的群落状态显示出随机的微生物群组合,并在婴儿期持续存在高病原体负荷。相比之下,双歧杆菌(特别是长双歧杆菌,尤其是前双歧杆菌)主导的群落状态则表现出稳定的集结轨迹和长期的抗病原体定植能力,这可能是由于菌株对富含母乳的新生儿饮食的特异性功能适应所致。与我们的人类队列观察结果一致,布氏杆菌在无菌小鼠模型中表现出优先效应并赋予病原体定植抵抗力。我们的研究结果证实了双歧杆菌作为主要定植菌在塑造生命早期微生物群组合和功能方面的关键作用。
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引用次数: 0
An intranuclear bacterial parasite of deep-sea mussels expresses apoptosis inhibitors acquired from its host 深海贻贝的核内细菌寄生虫表达从宿主那里获得的细胞凋亡抑制剂
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-06 DOI: 10.1038/s41564-024-01808-5
Miguel Ángel González Porras, Adrien Assié, Målin Tietjen, Marlene Violette, Manuel Kleiner, Harald Gruber-Vodicka, Nicole Dubilier, Nikolaus Leisch
A limited number of bacteria are able to colonize the nuclei of eukaryotes. ‘Candidatus Endonucleobacter’ infects the nuclei of deep-sea mussels, where it replicates to ≥80,000 bacteria per nucleus and causes nuclei to swell to 50 times their original size. How these parasites are able to replicate and avoid apoptosis is not known. Dual RNA-sequencing transcriptomes of infected nuclei isolated using laser-capture microdissection revealed that ‘Candidatus Endonucleobacter’ does not obtain most of its nutrition from nuclear DNA or RNA. Instead, ‘Candidatus Endonucleobacter’ upregulates genes for importing and digesting sugars, lipids, amino acids and possibly mucin from its host. It likely prevents apoptosis of host cells by upregulating 7–13 inhibitors of apoptosis, proteins not previously seen in bacteria. Comparative phylogenetic analyses revealed that ‘Ca. Endonucleobacter’ acquired inhibitors of apoptosis through horizontal gene transfer from their hosts. Horizontal gene transfer from eukaryotes to bacteria is assumed to be rare, but may be more common than currently recognized. ‘Candidatus Endonucleobacter’ is a pathogen of deep-sea mussels that can successfully reproduce in the nuclei of its host by expressing inhibitors of apoptosis, likely acquired through horizontal gene transfer.
能够在真核生物细胞核中定植的细菌数量有限。内核拟杆菌 "感染深海贻贝的细胞核,每个细胞核复制≥80,000 个细菌,使细胞核膨胀到原来的 50 倍。这些寄生虫如何能够复制并避免凋亡尚不清楚。利用激光捕获显微切割技术分离的受感染细胞核的双 RNA 序列转录组显示,'内核杆菌'的大部分营养并非来自核 DNA 或 RNA。相反,'内核杆菌'会上调从宿主体内输入和消化糖类、脂类、氨基酸以及可能的粘蛋白的基因。它可能通过上调 7-13 种细胞凋亡抑制因子来防止宿主细胞凋亡,这些蛋白以前在细菌中从未见过。系统发育比较分析表明,'Ca.内核细菌'通过宿主的水平基因转移获得了细胞凋亡抑制因子。真核生物向细菌的水平基因转移被认为是罕见的,但可能比目前认识到的更为普遍。
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引用次数: 0
Continental-scale associations of Arabidopsis thaliana phyllosphere members with host genotype and drought 拟南芥叶球成员与寄主基因型和干旱的大陆尺度关系
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-06 DOI: 10.1038/s41564-024-01773-z
Talia L. Karasov, Manuela Neumann, Laura Leventhal, Efthymia Symeonidi, Gautam Shirsekar, Aubrey Hawks, Grey Monroe, Pathodopsis Team, Moisés Exposito-Alonso, Joy Bergelson, Detlef Weigel, Rebecca Schwab
Plants are colonized by distinct pathogenic and commensal microbiomes across different regions of the globe, but the factors driving their geographic variation are largely unknown. Here, using 16S ribosomal DNA and shotgun sequencing, we characterized the associations of the Arabidopsis thaliana leaf microbiome with host genetics and climate variables from 267 populations in the species’ native range across Europe. Comparing the distribution of the 575 major bacterial amplicon variants (phylotypes), we discovered that microbiome composition in A. thaliana segregates along a latitudinal gradient. The latitudinal clines in microbiome composition are predicted by metrics of drought, but also by the spatial genetics of the host. To validate the relative effects of drought and host genotype we conducted a common garden field study, finding 10% of the core bacteria to be affected directly by drought and 20% to be affected by host genetic associations with drought. These data provide a valuable resource for the plant microbiome field, with the identified associations suggesting that drought can directly and indirectly shape genetic variation in A. thaliana via the leaf microbiome. The leaf microbiome compositions of 267 Arabidopsis thaliana populations across Europe reveal associations with climate and plant genetics.
在全球不同地区,植物被不同的病原微生物群和共生微生物群定植,但驱动其地理变异的因素在很大程度上是未知的。在这里,我们利用 16S 核糖体 DNA 和枪式测序技术,对拟南芥叶片微生物组与宿主遗传学和气候变量之间的关系进行了表征,这些微生物组来自拟南芥原产地欧洲的 267 个种群。通过比较 575 个主要细菌扩增子变体(系统型)的分布,我们发现拟南芥叶片微生物组的组成是沿着纬度梯度分离的。微生物组组成的纬度梯度是由干旱指标以及宿主的空间遗传学预测的。为了验证干旱和宿主基因型的相对影响,我们进行了一项普通花园田间研究,发现10%的核心细菌直接受干旱影响,20%的核心细菌受宿主基因与干旱相关性的影响。这些数据为植物微生物组领域提供了宝贵的资源,已确定的关联表明,干旱可以通过叶片微生物组直接或间接地影响连翘的遗传变异。
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引用次数: 0
Mycobacterium tuberculosis virulence lipid PDIM inhibits autophagy in mice 结核分枝杆菌毒脂 PDIM 可抑制小鼠的自噬作用
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-06 DOI: 10.1038/s41564-024-01797-5
Ekansh Mittal, G. V. R. Krishna Prasad, Sandeep Upadhyay, Jully Sadadiwala, Andrew J. Olive, Guozhe Yang, Christopher M. Sassetti, Jennifer A. Philips
Mycobacterium tuberculosis (Mtb) infects several lung macrophage populations, which have distinct abilities to restrict Mtb. What enables Mtb survival in certain macrophage populations is not well understood. Here we used transposon sequencing analysis of Mtb in wild-type and autophagy-deficient mouse macrophages lacking ATG5 or ATG7, and found that Mtb genes involved in phthiocerol dimycocerosate (PDIM) virulence lipid synthesis confer resistance to autophagy. Using ppsD mutant Mtb, we found that PDIM inhibits LC3-associated phagocytosis (LAP) by inhibiting phagosome recruitment of NADPH oxidase. In mice, PDIM protected Mtb from LAP and classical autophagy. During acute infection, PDIM was dispensable for Mtb survival in alveolar macrophages but required for survival in non-alveolar macrophages in an autophagy-dependent manner. During chronic infection, autophagy-deficient mice succumbed to infection with PDIM-deficient Mtb, with impairments in B-cell accumulation in lymphoid follicles. These findings demonstrate that PDIM contributes to Mtb virulence and immune evasion, revealing a contributory role for autophagy in B-cell responses. Mycobacterial phthiocerol dimycocerosate (PDIM) inhibits LC3-associated phagocytosis and counters autophagy-dependent restriction of Mycobacterium tuberculosis in non-alveolar macrophages.
结核分枝杆菌(Mtb)会感染多种肺部巨噬细胞群,这些巨噬细胞群具有不同的限制 Mtb 的能力。Mtb在某些巨噬细胞群中存活的原因尚不清楚。在这里,我们利用转座子测序分析了野生型和缺乏ATG5或ATG7的自噬缺陷型小鼠巨噬细胞中的Mtb,发现参与噬菌醇二甲基椰油酸盐(PDIM)毒脂合成的Mtb基因具有抗自噬能力。利用ppsD突变体Mtb,我们发现PDIM通过抑制吞噬体招募NADPH氧化酶来抑制LC3相关吞噬作用(LAP)。在小鼠体内,PDIM能保护Mtb免受LAP和经典自噬的影响。在急性感染期间,PDIM对于Mtb在肺泡巨噬细胞中的存活是不可或缺的,但对于非肺泡巨噬细胞中的存活则是必需的,其方式依赖于自噬。在慢性感染期间,自噬缺陷小鼠在感染PDIM缺陷的Mtb后死亡,淋巴滤泡中的B细胞积累出现障碍。这些研究结果表明,PDIM有助于Mtb的毒力和免疫逃避,揭示了自噬在B细胞反应中的作用。
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引用次数: 0
Discovery of CO2 tolerance genes associated with virulence in the fungal pathogen Cryptococcus neoformans 发现与真菌病原体新生隐球菌毒力有关的二氧化碳耐受基因
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-04 DOI: 10.1038/s41564-024-01792-w
Benjamin J. Chadwick, Laura C. Ristow, Xiaofeng Xie, Damian J. Krysan, Xiaorong Lin
Cryptococcus neoformans is a ubiquitous soil fungus and airborne pathogen that causes over 180,000 deaths each year. Cryptococcus must adapt to host CO2 levels to cause disease, but the genetic basis for this adaptation is unknown. We utilized quantitative trait loci mapping with 374 progeny from a cross between a CO2-tolerant clinical isolate and a CO2-sensitive environmental isolate to identify genetic regions regulating CO2 tolerance. To identify specific quantitative trait genes, we applied fine mapping through bulk segregant analysis of near-isogenic progeny with distinct tolerance levels to CO2. We found that virulence among near-isogenic strains in a murine model of cryptococcosis correlated with CO2 tolerance. Moreover, we discovered that sensitive strains may adapt in vivo to become more CO2 tolerant and more virulent. These findings highlight the underappreciated role of CO2 tolerance and its importance in the ability of an opportunistic environmental pathogen to cause disease. Quantitative trait loci mapping reveals that tolerance to host CO2 is critical for virulence of the human fungal pathogen Cryptococcus neoformans.
新型隐球菌是一种无处不在的土壤真菌和空气传播病原体,每年导致超过 18 万人死亡。隐球菌必须适应寄主的二氧化碳水平才能致病,但这种适应的遗传基础尚不清楚。我们利用对二氧化碳耐受的临床分离株和对二氧化碳敏感的环境分离株杂交产生的 374 个后代的数量性状位点图谱来确定调控二氧化碳耐受性的遗传区域。为了确定特定的数量性状基因,我们对具有不同二氧化碳耐受水平的近等基因后代进行了大量分离分析,从而进行了精细图谱绘制。我们发现,在小鼠隐球菌病模型中,近等基因株的毒力与二氧化碳耐受性相关。此外,我们还发现,敏感菌株可能会在体内发生适应性变化,变得更耐受二氧化碳,毒性也更强。这些发现凸显了二氧化碳耐受性在机会性环境病原体致病能力中被低估的作用及其重要性。
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引用次数: 0
Diverse RNA viruses of parasitic nematodes can elicit antibody responses in vertebrate hosts 寄生线虫的多种 RNA 病毒可引起脊椎动物宿主的抗体反应
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-04 DOI: 10.1038/s41564-024-01796-6
Shannon Quek, Amber Hadermann, Yang Wu, Lander De Coninck, Shrilakshmi Hegde, Jordan R. Boucher, Jessica Cresswell, Ella Foreman, Andrew Steven, E. James LaCourse, Stephen A. Ward, Samuel Wanji, Grant L. Hughes, Edward I. Patterson, Simon C. Wagstaff, Joseph D. Turner, Rhys H. Parry, Alain Kohl, Eva Heinz, Kenneth Bentum Otabil, Jelle Matthijnssens, Robert Colebunders, Mark J. Taylor
Parasitic nematodes have an intimate, chronic and lifelong exposure to vertebrate tissues. Here we mined 41 published parasitic nematode transcriptomes from vertebrate hosts and identified 91 RNA viruses across 13 virus orders from 24 families in ~70% (28 out of 41) of parasitic nematode species, which include only 5 previously reported viruses. We observe widespread distribution of virus–nematode associations across multiple continents, suggesting an ancestral acquisition event and host–virus co-evolution. Characterization of viruses of Brugia malayi (BMRV1) and Onchocerca volvulus (OVRV1) shows that these viruses are abundant in reproductive tissues of adult parasites. Importantly, the presence of BMRV1 RNA in B. malayi parasites mounts an RNA interference response against BMRV1 suggesting active viral replication. Finally, BMRV1 and OVRV1 were found to elicit antibody responses in serum samples from infected jirds and infected or exposed humans, indicating direct exposure to the immune system. Transcriptome mining, phylogenetic analysis, bioimaging and serology experiments reveal a widespread diverse virome present in ~70% of parasitic nematodes, such as Brugia malayi and Onchocerca volvulus, where some viruses are abundant in the reproductive tract and are associated with seropositivity in vertebrate hosts.
寄生线虫与脊椎动物组织有着密切、长期和终生的接触。在这里,我们从脊椎动物宿主中挖掘了 41 个已发表的寄生线虫转录组,在约 70% 的寄生线虫物种(41 个物种中有 28 个物种)中发现了 24 个科 13 个病毒目中的 91 种 RNA 病毒,其中仅包括 5 种以前报道过的病毒。我们观察到病毒与线虫的关联广泛分布于多个大洲,这表明存在祖先获取病毒的事件以及宿主与病毒的共同进化。对马来布鲁氏菌(BMRV1)和盘尾丝虫病(OVRV1)病毒的特性分析表明,这些病毒大量存在于成年寄生虫的生殖组织中。重要的是,马来线虫寄生虫中 BMRV1 RNA 的存在会引发针对 BMRV1 的 RNA 干扰反应,这表明病毒复制活跃。最后,研究发现 BMRV1 和 OVRV1 能在受感染的鸟类和受感染或暴露的人类血清样本中引起抗体反应,这表明病毒直接暴露于免疫系统。
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引用次数: 0
We must learn from past outbreaks 我们必须从过去的疫情中吸取教训。
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-03 DOI: 10.1038/s41564-024-01813-8
To successfully tackle the current mpox public-health emergency, we must learn from past outbreaks to focus research questions and take collaborative action.
要成功应对当前的麻风腮公共卫生紧急状况,我们必须从过去的疫情中吸取教训,聚焦研究问题并采取合作行动。
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引用次数: 0
Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in Candida albicans 单细胞检测拷贝数变化揭示白念珠菌对抗真菌药物的动态适应机制
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-03 DOI: 10.1038/s41564-024-01795-7
Xin Zhou, Audrey Hilk, Norma V. Solis, Nancy Scott, Annette Beach, Natthapon Soisangwan, Clara L. Billings, Laura S. Burrack, Scott G. Filler, Anna Selmecki
Genomic copy number changes are associated with antifungal drug resistance and virulence across diverse fungal pathogens, but the rate and dynamics of these genomic changes in the presence of antifungal drugs are unknown. Here we optimized a dual-fluorescent reporter system in the diploid pathogen Candida albicans to quantify haplotype-specific copy number variation (CNV) and loss of heterozygosity (LOH) at the single-cell level with flow cytometry. We followed the frequency and dynamics of CNV and LOH at two distinct genomic locations in the presence and absence of antifungal drugs in vitro and in a murine model of candidiasis. Copy number changes were rapid and dynamic during adaptation to fluconazole and frequently involved competing subpopulations with distinct genotypes. This study provides quantitative evidence for the rapid speed at which diverse genotypes arise and undergo dynamic population-level fluctuations during adaptation to antifungal drugs in vitro and in vivo. Development of a dual-fluorescent reporter system allows rapid quantification of diverse genomic copy number changes that arise in Candida albicans during adaptation to antifungal drugs.
基因组拷贝数变化与各种真菌病原体的抗真菌药物耐药性和毒力有关,但这些基因组变化在抗真菌药物作用下的速率和动态尚不清楚。在这里,我们优化了二倍体病原体白色念珠菌的双荧光报告系统,利用流式细胞仪在单细胞水平上量化单倍型特异性拷贝数变异(CNV)和杂合性缺失(LOH)。我们跟踪了体外和小鼠念珠菌病模型中抗真菌药物存在和不存在时,两个不同基因组位置的 CNV 和 LOH 的频率和动态变化。在对氟康唑的适应过程中,拷贝数的变化是快速和动态的,而且经常涉及具有不同基因型的竞争亚群。这项研究提供了定量证据,证明在体外和体内适应抗真菌药物的过程中,不同基因型的出现和种群水平的动态波动速度很快。
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引用次数: 0
Individual bacterial cells can use spatial sensing of chemical gradients to direct chemotaxis on surfaces 单个细菌细胞可以利用对化学梯度的空间感知来引导表面的趋化运动
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-09-02 DOI: 10.1038/s41564-024-01729-3
James H. R. Wheeler, Kevin R. Foster, William M. Durham
Swimming bacteria navigate chemical gradients using temporal sensing to detect changes in concentration over time. Here we show that surface-attached bacteria use a fundamentally different mode of sensing during chemotaxis. We combined microfluidic experiments, massively parallel cell tracking and fluorescent reporters to study how Pseudomonas aeruginosa senses chemical gradients during pili-based ‘twitching’ chemotaxis on surfaces. Unlike swimming cells, we found that temporal changes in concentration did not induce motility changes in twitching cells. We then quantified the chemotactic behaviour of stationary cells by following changes in the sub-cellular localization of fluorescent proteins as cells are exposed to a gradient that alternates direction. These experiments revealed that P. aeruginosa cells can directly sense differences in concentration across the lengths of their bodies, even in the presence of strong temporal fluctuations. Our work thus overturns the widely held notion that bacterial cells are too small to directly sense chemical gradients in space. Microfluidic experiments reveal that surface-attached Pseudomonas aeruginosa cells directly sense differences in chemical concentration across the length of their cell bodies to guide pili-based chemotaxis.
游动细菌利用时间感应来探测化学梯度随时间的浓度变化。在这里,我们展示了表面附着细菌在趋化过程中使用的一种根本不同的感知模式。我们将微流体实验、大规模并行细胞追踪和荧光报告结合起来,研究了铜绿假单胞菌在基于绒毛的表面 "抽动 "趋化过程中如何感知化学梯度。与游动细胞不同,我们发现浓度的时间变化不会引起抽动细胞的运动变化。然后,我们通过跟踪细胞暴露在方向交替的梯度中时荧光蛋白亚细胞定位的变化,量化了静止细胞的趋化行为。这些实验揭示了铜绿微囊藻细胞即使在强烈的时间波动下,也能直接感知整个细胞长度上的浓度差异。因此,我们的研究推翻了人们普遍认为的细菌细胞太小而无法直接感知空间化学梯度的观点。
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引用次数: 0
Neurospora intermedia from a traditional fermented food enables waste-to-food conversion 从传统发酵食品中提取的中间神经孢子菌实现了变废为宝
IF 20.5 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-08-29 DOI: 10.1038/s41564-024-01799-3
Vayu Maini Rekdal, José Manuel Villalobos-Escobedo, Nabila Rodriguez-Valeron, Mikel Olaizola Garcia, Diego Prado Vásquez, Alexander Rosales, Pia M. Sörensen, Edward E. K. Baidoo, Ana Calheiros de Carvalho, Robert Riley, Anna Lipzen, Guifen He, Mi Yan, Sajeet Haridas, Christopher Daum, Yuko Yoshinaga, Vivian Ng, Igor V. Grigoriev, Rasmus Munk, Christofora Hanny Wijaya, Lilis Nuraida, Isty Damayanti, Pablo Cruz-Morales, Jay. D. Keasling
Fungal fermentation of food and agricultural by-products holds promise for improving food sustainability and security. However, the molecular basis of fungal waste-to-food upcycling remains poorly understood. Here we use a multi-omics approach to characterize oncom, a fermented food traditionally produced from soymilk by-products in Java, Indonesia. Metagenomic sequencing of samples from small-scale producers in Western Java indicated that the fungus Neurospora intermedia dominates oncom. Further transcriptomic, metabolomic and phylogenomic analysis revealed that oncom-derived N. intermedia utilizes pectin and cellulose degradation during fermentation and belongs to a genetically distinct subpopulation associated with human-generated by-products. Finally, we found that N. intermedia grew on diverse by-products such as fruit and vegetable pomace and plant-based milk waste, did not encode mycotoxins, and could create foods that were positively perceived by consumers outside Indonesia. These results showcase the traditional significance and future potential of fungal fermentation for creating delicious and nutritious foods from readily available by-products. A multi-omics analysis of oncom, an Indonesian fermented food made from soymilk waste, shows how associated fungi break down food waste to yield nutritious and positively received foods.
真菌发酵食品和农副产品有望提高食品的可持续性和安全性。然而,人们对真菌废物转化为食品的分子基础仍然知之甚少。在这里,我们使用多组学方法来描述印尼爪哇传统上用豆浆副产品生产的发酵食品 oncom 的特征。对来自爪哇西部小规模生产者的样本进行的元基因组测序表明,Neurospora intermedia 真菌在 oncom 中占主导地位。进一步的转录组、代谢组和系统发生组分析表明,oncom 衍生的 N. intermedia 在发酵过程中利用果胶和纤维素降解,属于与人类产生的副产品相关的基因独特亚群。最后,我们发现 N. intermedia 可在多种副产品(如果蔬渣和植物性牛奶废料)上生长,不会产生霉菌毒素,并能制作出印尼以外消费者喜爱的食品。这些结果展示了真菌发酵的传统意义和未来潜力,即利用现成的副产品制作美味营养的食品。
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引用次数: 0
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Nature Microbiology
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