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Gut microbiota modulates neurotransmitter and gut-brain signaling 肠道微生物群调节神经递质和肠脑信号传导
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-26 DOI: 10.1016/j.micres.2024.127858
Shiyan Qu , Zijin Yu , Yaxuan Zhou , Shiyi Wang , Minqi Jia , Ti Chen , Xiaojie Zhang

Neurotransmitters, including 5-hydroxytryptamine (5-HT), dopamine (DA), gamma-aminobutyric acid (GABA), and glutamate, are essential transductors in the Gut-Brain Axis (GBA), playing critical roles both peripherally and centrally. Accumulating evidence suggests that the gut microbiota modulates intestinal neurotransmitter metabolism and gut-to-brain signaling, shedding light on the crucial role of the gut microbiota in brain function and the pathogenesis of various neuropsychiatric diseases, such as major depression disorder (MDD), anxiety, addiction and Parkinson's disease (PD). Despite the exciting findings, the mechanisms underlying the modulation of neurotransmitter metabolism and function by the gut microbiota are still being elucidated. In this review, we aim to provide a comprehensive overview of the existing knowledge about the role of the gut microbiota in neurotransmitter metabolism and function in animal and clinical experiments. Moreover, we will discuss the potential mechanisms through which gut microbiota-derived neurotransmitters contribute to the pathogenesis of neuropsychiatric diseases, thus highlighting a novel therapeutic target for these conditions.

神经递质,包括5-羟色胺(5-HT)、多巴胺(DA)、γ-氨基丁酸(GABA)和谷氨酸,是肠-脑轴(GBA)的重要传导因子,在外周和中枢发挥着关键作用。越来越多的证据表明,肠道微生物群会调节肠道神经递质代谢和肠道到大脑的信号传导,从而揭示了肠道微生物群在大脑功能和各种神经精神疾病(如重度抑郁症(MDD)、焦虑症、成瘾症和帕金森病(PD))发病机制中的关键作用。尽管研究结果令人振奋,但肠道微生物群调节神经递质代谢和功能的机制仍有待阐明。在这篇综述中,我们旨在全面概述现有的动物和临床实验中有关肠道微生物群在神经递质代谢和功能中的作用的知识。此外,我们还将讨论肠道微生物群衍生的神经递质导致神经精神疾病发病机制的潜在机制,从而突出这些疾病的新型治疗靶点。
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引用次数: 0
Cervicovaginal microbiome, high-risk HPV infection and cervical cancer: Mechanisms and therapeutic potential 宫颈阴道微生物组、高危 HPV 感染与宫颈癌:机制与治疗潜力
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-26 DOI: 10.1016/j.micres.2024.127857
Roujie Huang , Zimo Liu , Tianshu Sun , Lan Zhu

The microbiota in the female genital tract is an intricate assembly of diverse aerobic, anaerobic, and microaerophilic microorganisms, which share the space within the reproductive tract and engage in complex interactions. Microbiome dysbiosis may disrupt the symbiotic relationship between the host and microorganisms and play a pivotal role in the pathogenesis of various diseases, including its involvement in the establishment of human papillomavirus (HPV)-associated cervical cancer (CC). Interventions to restore microbiota homeostasis (e.g., probiotics) and bacterial-vector HPV therapeutic vaccines have been reported to be potentially effective in clearing HPV infection and ameliorating cytological abnormalities. In this review, we place emphasis on elucidating the alterations within the cervical–vaginal microbiota as well as the intratumoral microbiota in the context of high-risk HPV (HR-HPV) infection and its subsequent progression to cervical intraepithelial neoplasia/CC. Furthermore, we explore the mechanisms by which these microbial communities exert potential pathogenic or protective effects, including modulating genital inflammation and immune responses, affecting HR-HPV oncogene expression and oncoprotein production, regulating oxidative stress and deoxyribonucleic acid (DNA) damage, and inducing metabolic rewiring. Lastly, we summarize the latest evidence in human trials regarding the efficacy of probiotics, prebiotics and probiotic-vector HPV therapeutic vaccines. This review aims to foster a deeper understanding of the role of the microbiota in HR-HPV infection-related cervix cancer development, and further provide a theoretical basis for the development of preventive and therapeutic strategies based on microbial modulation.

女性生殖道中的微生物群是由多种需氧、厌氧和微嗜氧微生物组成的复杂集合体,它们共享生殖道内的空间并进行复杂的相互作用。微生物群失调可能会破坏宿主与微生物之间的共生关系,并在各种疾病的发病机制中发挥关键作用,包括参与人乳头状瘤病毒(HPV)相关宫颈癌(CC)的形成。据报道,恢复微生物群平衡的干预措施(如益生菌)和细菌载体 HPV 治疗疫苗可能会有效清除 HPV 感染并改善细胞学异常。在这篇综述中,我们将重点阐明在高危型 HPV(HR-HPV)感染及其随后发展为宫颈上皮内瘤变/CC 的过程中,宫颈阴道微生物群和瘤体内微生物群的改变。此外,我们还探讨了这些微生物群落发挥潜在致病或保护作用的机制,包括调节生殖器炎症和免疫反应、影响 HR-HPV 肿瘤基因的表达和肿瘤蛋白的产生、调节氧化应激和脱氧核糖核酸(DNA)损伤以及诱导代谢重构。最后,我们总结了益生菌、益生元和益生菌载体人乳头瘤病毒治疗疫苗疗效的最新人体试验证据。本综述旨在加深人们对微生物群在与HR-HPV感染相关的宫颈癌发展中的作用的理解,并进一步为开发基于微生物调节的预防和治疗策略提供理论依据。
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引用次数: 0
Multi-omics analysis reveals the effects of three application modes of plant growth promoting microbes biofertilizer on potato (Solanum tuberosum L.) growth under alkaline loess conditions 多组学分析揭示三种植物生长促进微生物生物肥料施用模式对碱性黄土条件下马铃薯(Solanum tuberosum L.)生长的影响
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-25 DOI: 10.1016/j.micres.2024.127855
Yuan Tian , Yang Liu , Liang Yue , Xia Zhao , Qin Zhou , Constantine Uwaremwe , Yun Wang , Gaofeng Chen , Yuexia Sha , Yubao Zhang , Ruoyu Wang

Potato is an important crop due to its high contents of starch, protein, and various vitamins and minerals. Biofertilizers are composed of plant growth promoting microbes (PGPMs) which are essential for improving the growth and resistance of potato. However, little information has focused on the modes of inoculation of biofertilizers on plant growth and microecology. This study aims to reveal the response mechanism of the potato to three modes of inoculation of biofertilizers all containing PGPM Bacillus amyloliquefaciens EZ99, i.e. scattered mode of 5 kg/ha biofertilizer (M5), soaking seed tubers with dissolved 5 kg/ha biofertilizer (MZG), and scattered mode of 3 kg/ha biofertilizer + 2 kg/ha sucrose (MY34) in alkaline loess field through multi-omics analysis of transcriptome, metabolome and microbiome. The physiological result revealed that two application modes of equal amount of biofertilizer M5 and MZG significantly improved the growth and yield of potatoes. Furthermore, the transcriptome of potato exhibited sets of differentially expressed genes enriched in photosynthesis, sugar metabolism, and phenylpropanoid biosynthesis among the three modes, with the M5 mode exhibiting overall up-regulation of 828 genes. Based on the untargeted metabolomic analysis of potato tuber, M5 mode significantly accumulated sucrose, while MZG and MY34 mode significantly accumulated the stress metabolites euchrenone b6 and mannobiose, respectively. Besides, the microbial structure of potato rhizosphere showed that the diversity of bacteria and fungi was similar in all soils, but their abundances varied significantly. Specifically, beneficial Penicillium was enriched in M5 and MZG soils, whereas MY34 soil accumulated potential pathogens Plectosphaerella and saccharophilic Mortierella. Collectively, these e findings highlight that MZG is the most effective mode to promote potato growth and stimulate rhizosphere effect. The present study not only encourages sustainable agriculture through agroecological practices, but also provides broad prospects for the application of PGPM biofertilizer in staple foods.

马铃薯是一种重要的农作物,因为它含有大量淀粉、蛋白质以及各种维生素和矿物质。生物肥料由植物生长促进微生物(PGPMs)组成,对改善马铃薯的生长和抗性至关重要。然而,有关接种生物肥料对植物生长和微生态的影响模式的信息却很少。本研究旨在揭示马铃薯对含有淀粉芽孢杆菌 EZ99 的三种生物肥料接种模式的反应机制,即通过对转录组、代谢组和微生物组的多组学分析,发现在碱性黄土地上,马铃薯对三种接种生物肥料(均含有 PGPM 直链芽孢杆菌 EZ99)的模式,即每公顷 5 千克生物肥料的分散接种模式(M5)、用溶解的每公顷 5 千克生物肥料浸泡块茎种子的接种模式(MZG)和每公顷 3 千克生物肥料+每公顷 2 千克蔗糖的分散接种模式(MY34)。生理结果表明,等量施用生物肥 M5 和 MZG 可显著提高马铃薯的生长和产量。此外,马铃薯的转录组显示,三种施肥模式在光合作用、糖代谢和苯丙类生物合成方面富集了多组差异表达基因,其中 M5 模式总体上调了 828 个基因。根据马铃薯块茎的非靶向代谢组学分析,M5模式显著积累蔗糖,而MZG和MY34模式分别显著积累胁迫代谢产物优克龙b6和甘露寡糖。此外,马铃薯根瘤菌层的微生物结构表明,所有土壤中细菌和真菌的多样性相似,但丰度差异很大。具体而言,M5 和 MZG 土壤中富含有益的青霉,而 MY34 土壤中则富含潜在的病原菌 Plectosphaerella 和嗜糖 Mortierella。总之,这些发现突出表明,MZG 是促进马铃薯生长和刺激根瘤效应的最有效模式。本研究不仅鼓励通过农业生态实践实现农业的可持续发展,还为 PGPM 生物肥料在主食中的应用提供了广阔的前景。
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引用次数: 0
A bud's life: Metabarcoding analysis to characterise hazelnut big buds microbiome biodiversity 花蕾的一生:通过代谢编码分析确定榛子大花蕾微生物群生物多样性的特征
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-24 DOI: 10.1016/j.micres.2024.127851
Silvia Turco , Federico Brugneti , Irene Giubilei , Cristian Silvestri , Miloš Petrović , Mounira Inas Drais , Valerio Cristofori , Stefano Speranza , Angelo Mazzaglia , Mario Contarini , Luca Rossini

Despite Corylus avellana L. being an economically important shrub species known for its resilience to adverse environmental conditions, it constantly faces attacks from a plethora of biotic entities. Among these, the mite pest Phytoptus avellanae is gaining importance, causing economic losses every year. This mite colonises the new generative and vegetative buds, leading them to become swollen and reddish, and drastically reducing hazelnut production. The biology behind gall formation is still poorly understood. This study provides a qualitative and quantitative description of the microbiome in both healthy and infested buds of two economically important hazelnut cultivars through metabarcoding of fungal ITS and bacterial 16 S. Potentially pathogenic genera such as Fusarium and Pseudomonas were predominant in the infested buds, along with the obligate intracellular bacterial genus Wolbachia. Akanthomyces muscarius was instead isolated from culture-based methods only from the infested buds. These findings could improve the understanding of gall ecology, supporting the management of mite populations, and they could also serve as a milestone for further studies on low-impact, monitoring-driven, and genetically targeted control strategies.

尽管 L. 是一种具有重要经济价值的灌木物种,以其对不利环境条件的适应能力而闻名,但它始终面临着大量生物实体的攻击。其中,螨类害虫越来越重要,每年都会造成经济损失。这种螨虫会在榛子的新芽和无性生殖芽上定殖,导致新芽肿胀发红,大大降低了榛子的产量。人们对虫瘿形成背后的生物学原理还知之甚少。本研究通过对真菌 ITS 和细菌 16S 进行代谢编码,对两个具有重要经济价值的榛子栽培品种的健康芽和受侵染芽中的微生物组进行了定性和定量描述。在受侵染的花蕾中,潜在的致病菌属(如和)占主导地位,而只能通过培养方法从受侵染的花蕾中分离出细胞内细菌属。这些发现可以提高人们对瘿蚊生态学的认识,为螨虫种群的管理提供支持,同时也是进一步研究低影响、监测驱动和基因靶向控制策略的里程碑。
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引用次数: 0
Bacillus paralicheniformis, an acetate-producing probiotic, alleviates ulcerative colitis via protecting the intestinal barrier and regulating the NLRP3 inflammasome 副坏死性芽孢杆菌是一种能产生醋酸盐的益生菌,它能通过保护肠道屏障和调节 NLRP3 炎症小体来缓解溃疡性结肠炎
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-23 DOI: 10.1016/j.micres.2024.127856
Nini Dai , Xinting Yang , Peilong Pan , Guanghui Zhang , Kangliang Sheng , Jingmin Wang , Xiao Liang , Yongzhong Wang

Ulcerative colitis (UC) presents a challenging scenario in digestive health, characterized by recurrent inflammation that is often hard to manage. Bacteria capable of producing short-chain fatty acids (SCFAs) play a pivotal role in mitigating UC symptoms, rendering them promising candidates for probiotic therapy. In this investigation, we assessed the impact of Bacillus paralicheniformis HMPM220325 on dextran sodium sulfate (DSS)-induced UC in mice. Genomic analysis of the strain revealed the presence of protease genes associated with acetate and butyrate synthesis, with acetic acid detected in its fermentation broth. Administration of B. paralicheniformis HMPM220325 to UC mice ameliorated pathological manifestations of the condition and restored intestinal barrier function. Furthermore, B. paralicheniformis HMPM220325 suppressed the activation of the NLRP3 inflammasome signaling pathway and modulated the composition of the intestinal microbiota. These findings shed significant light on the potential of B. paralicheniformis as a probiotic candidate, offering a novel avenue for the prevention and therapeutic intervention of colitis.

溃疡性结肠炎(UC)是消化系统健康的一大挑战,其特点是炎症反复发作,往往难以控制。能够产生短链脂肪酸(SCFAs)的细菌在减轻 UC 症状方面发挥着关键作用,因此很有希望成为益生菌疗法的候选菌。在这项研究中,我们评估了 HMPM220325 对右旋糖酐硫酸钠(DSS)诱导的小鼠 UC 的影响。对该菌株的基因组分析表明,它含有与乙酸盐和丁酸盐合成相关的蛋白酶基因,其发酵液中还检测到乙酸。给 UC 小鼠服用 HMPM220325 可改善病理表现,恢复肠道屏障功能。此外,HMPM220325 还能抑制 NLRP3 炎性体信号通路的激活,并调节肠道微生物群的组成。这些发现揭示了 HMPM220325 作为候选益生菌的潜力,为结肠炎的预防和治疗干预提供了一条新途径。
{"title":"Bacillus paralicheniformis, an acetate-producing probiotic, alleviates ulcerative colitis via protecting the intestinal barrier and regulating the NLRP3 inflammasome","authors":"Nini Dai ,&nbsp;Xinting Yang ,&nbsp;Peilong Pan ,&nbsp;Guanghui Zhang ,&nbsp;Kangliang Sheng ,&nbsp;Jingmin Wang ,&nbsp;Xiao Liang ,&nbsp;Yongzhong Wang","doi":"10.1016/j.micres.2024.127856","DOIUrl":"10.1016/j.micres.2024.127856","url":null,"abstract":"<div><p>Ulcerative colitis (UC) presents a challenging scenario in digestive health, characterized by recurrent inflammation that is often hard to manage. Bacteria capable of producing short-chain fatty acids (SCFAs) play a pivotal role in mitigating UC symptoms, rendering them promising candidates for probiotic therapy. In this investigation, we assessed the impact of <em>Bacillus paralicheniformis</em> HMPM220325 on dextran sodium sulfate (DSS)-induced UC in mice. Genomic analysis of the strain revealed the presence of protease genes associated with acetate and butyrate synthesis, with acetic acid detected in its fermentation broth. Administration of <em>B. paralicheniformis</em> HMPM220325 to UC mice ameliorated pathological manifestations of the condition and restored intestinal barrier function. Furthermore, <em>B. paralicheniformis</em> HMPM220325 suppressed the activation of the NLRP3 inflammasome signaling pathway and modulated the composition of the intestinal microbiota. These findings shed significant light on the potential of <em>B. paralicheniformis</em> as a probiotic candidate, offering a novel avenue for the prevention and therapeutic intervention of colitis.</p></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"287 ","pages":"Article 127856"},"PeriodicalIF":6.1,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular and eco-physiological responses of soil-borne lead (Pb2+)-resistant bacteria for bioremediation and plant growth promotion under lead stress 抗土壤中铅(Pb2+)细菌在铅胁迫下进行生物修复和促进植物生长的分子和生态生理反应
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-22 DOI: 10.1016/j.micres.2024.127831
Priyanka Pal , Krishnendu Pramanik , Sudip Kumar Ghosh , Sayanta Mondal , Tanushree Mondal , Tithi Soren , Tushar Kanti Maiti

Lead (Pb) is the 2nd known portentous hazardous substance after arsenic (As). Being highly noxious, widespread, non-biodegradable, prolonged environmental presence, and increasing accumulation, particularly in arable land, Pb pollution has become a serious global health concern requiring urgent remediation. Soil-borne, indigenous microbes from Pb-polluted sites have evolved diverse resistance strategies, involving biosorption, bioprecipitation, biomineralization, biotransformation, and efflux mechanisms, under continuous exposure to Pb in human-impacted surroundings. These strategies employ a wide range of functional bioligands to capture Pb and render it inaccessible for leaching. Recent breakthroughs in molecular technology and understanding of lead resistance mechanisms offer the potential for utilizing microbes as biological tools in environmental risk assessment. Leveraging the specific affinity and sensitivity of bacterial regulators to Pb2+ ions, numerous lead biosensors have been designed and deployed worldwide to monitor Pb bioavailability in contaminated sites, even at trace levels. Besides, the ongoing degradation of croplands due to Pb pollution poses a significant challenge to meet the escalating global food demands. The accumulation of Pb in plant tissues jeopardizes both food safety and security while severely impacting plant growth. Exploring Pb-resistant plant growth-promoting rhizobacteria (PGPR) presents a promising sustainable approach to agricultural practices. The active associations of PGPR with host plants have shown enhancements in plant biomass and stress alleviation under Pb influence. They thus serve a dual purpose for plants grown in Pb-contaminated areas. This review aims to offer a comprehensive understanding of the role played by Pb-resistant soil-borne indigenous bacteria in expediting bioremediation and improving the growth of Pb-challenged plants essential for potential field application, thus broadening prospects for future research and development.

铅(Pb)是继砷(As)之后已知的第二大有害物质。铅污染具有剧毒性、广泛性、不可生物降解性、长期存在于环境中以及日益积累(尤其是在耕地中)等特点,已成为一个严重的全球健康问题,亟需采取补救措施。在受人类影响的环境中持续暴露于铅的情况下,来自铅污染地区的土生土长的微生物进化出了多种抗性策略,包括生物吸附、生物沉淀、生物矿化、生物转化和外排机制。这些策略利用各种功能性生物配体来捕获铅,使其无法被沥滤。分子技术的最新突破和对铅抗性机理的了解为利用微生物作为环境风险评估的生物工具提供了可能。利用细菌调节剂对铅离子的特异性亲和力和灵敏度,全球已设计并部署了大量铅生物传感器,用于监测受污染场地的铅生物利用率,甚至是痕量水平。此外,铅污染导致耕地不断退化,这对满足全球不断增长的粮食需求构成了重大挑战。铅在植物组织中的积累既危及食品安全,又严重影响植物生长。探索抗铅植物生长促进根瘤菌(PGPR)为农业实践提供了一种前景广阔的可持续方法。PGPR 与寄主植物的积极结合表明,在铅的影响下,植物的生物量会增加,压力会减轻。因此,它们对在铅污染地区种植的植物具有双重作用。本综述旨在全面介绍耐铅土生细菌在加快生物修复和改善受铅污染植物的生长方面所发挥的作用,这些作用对于潜在的实地应用至关重要,从而为未来的研究和开发开辟了广阔的前景。
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引用次数: 0
Berberine ameliorates vascular dysfunction by downregulating TMAO-endoplasmic reticulum stress pathway via gut microbiota in hypertension 小檗碱通过肠道微生物群下调 TMAO-内质网应激途径改善高血压患者的血管功能障碍
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-20 DOI: 10.1016/j.micres.2024.127824
Zhichao Wang , Yijia Shao , Fang Wu , Dangu Luo , Guoyifan He , Jianwen Liang , Xiaoqing Quan , Xiehui Chen , Wenhao Xia , Ye Chen , Yue Liu , Long Chen

The gut microbial metabolite trimethylamine N-oxide (TMAO) is regarded as a novel risk factor for hypertension. Berberine (BBR) exerts cardiovascular protective effects by regulating the gut microbiota-metabolite production pathway. However, whether and how BBR alleviates TMAO-induced vascular dysfunction in hypertension remains unclear. In the present study, we observed that plasma TMAO and related bacterial abundance were significantly elevated and negatively correlated with vascular function in 86 hypertensive patients compared with 46 normotensive controls. TMAO activated endoplasmic reticulum stress (ERS) signaling pathway to promote endothelial cell dysfunction and apoptosis in vitro. BBR (100, 200 mg · kg−1 ·d−1) for 4 weeks ameliorates TMAO-induced vascular dysfunction and ERS activation in a choline-angiotensin II hypertensive mouse model. We found that plasma TMAO levels in 15 hypertensive patients treated with BBR (0.4 g, tid) were reduced by 8.8 % and 16.7 % at months 1 and 3, respectively, compared with pretreatment baseline. The oral BBR treatment also improved vascular function and lowered blood pressure. Faecal 16 S rDNA showed that BBR altered the gut bacterial composition and reduced the abundance of CutC/D bacteria in hypertensive mice and patients. In vitro bacterial cultures and enzyme reaction systems indicated that BBR inhibited the biosynthesis of TMAO precursor in the gut microbiota by binding to and inhibiting the activity of CutC/D enzyme. Our results indicate that BBR improve vascular dysfunction at least partially by decreasing TMAO via regulation of the gut microbiota in hypertension.

肠道微生物代谢物三甲胺 N-氧化物(TMAO)被认为是高血压的新型风险因素。小檗碱(BBR)通过调节肠道微生物群-代谢物产生途径发挥保护心血管的作用。然而,小檗碱是否以及如何缓解 TMAO 引起的高血压血管功能障碍仍不清楚。在本研究中,我们观察到,与 46 例正常血压对照组相比,86 例高血压患者的血浆 TMAO 和相关细菌丰度显著升高,且与血管功能呈负相关。TMAO 在体外激活内质网应激(ERS)信号通路,促进内皮细胞功能障碍和凋亡。在胆碱-血管紧张素 II 高血压小鼠模型中,连续 4 周服用 BBR(100、200 毫克 - kg-1 -d-1)可改善 TMAO 诱导的血管功能障碍和 ERS 激活。我们发现,15 名高血压患者接受 BBR(0.4 克,tid)治疗后,血浆中的 TMAO 水平在第 1 个月和第 3 个月分别比治疗前的基线降低了 8.8% 和 16.7%。口服 BBR 还能改善血管功能并降低血压。粪便 16 S rDNA 显示,BBR 改变了高血压小鼠和患者的肠道细菌组成,降低了 CutC/D 细菌的丰度。体外细菌培养和酶反应系统表明,BBR 通过与 CutC/D 酶结合并抑制其活性,抑制了 TMAO 前体在肠道微生物群中的生物合成。我们的研究结果表明,BBR 至少可以通过调节高血压患者的肠道微生物群来减少 TMAO,从而部分改善血管功能障碍。
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引用次数: 0
Small RNA-regulated expression of efflux pump affects tigecycline resistance and heteroresistance in clinical isolates of Klebsiella pneumoniae 小核糖核酸调控的外排泵表达影响肺炎克雷伯氏菌临床分离株对替加环素的耐药性和异抗性。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-20 DOI: 10.1016/j.micres.2024.127825
Yuqiao Han , Yilin Xiong , Mengyao Wang , Jia Wang , Tao Song , Jing Yu , Jia Hu , Zinan Zhao , Ming Li , Ying Li , Yang Chen

Tigecycline and the newly Food and Drug Administration-approved tetracyclines, including eravacycline and omadacycline, are regarded as last-resort treatments for multidrug-resistant Enterobacterales. However, tigecycline resistance in Klebsiella pneumoniae has increased, especially the underlying mechanism of heteroresistance is unclear. This study aimed to elucidate the mechanisms underlying tigecycline resistance and heteroresistance in clinical K. pneumoniae isolates. A total of 153 clinical K. pneumoniae isolates were collected, and identified 15 tigecycline-resistant and three tigecycline-heteroresistant isolates using broth microdilution and population analysis profile methods, respectively. Total RNAs from K. pneumoniae ATCC13883 and the laboratory-induced tigecycline-resistant strain were extracted and sequenced on an Illumina platform. Differentially expressed genes and regulatory small RNAs (sRNAs) were analyzed and validated in clinical isolates of K. pneumoniae using quantitative real-time PCR. RNA sequencing results showed that mdtABC efflux pump genes were significantly upregulated in the tigecycline-resistant strains. Overexpression of mdtABC was observed in a clinical K. pneumoniae isolate, which increased tigecycline minimum inhibitory concentrations (MICs) and was involved in tigecycline heteroresistance. Sequencing analysis of sRNA demonstrated that candidate sRNA-120 directly interacted with the mdtABC operon and was downregulated in tigecycline-resistant strains. We generated an sRNA-120 deletion mutation strain and a complemented strain of K. pneumoniae. The sRNA-120 deletion strain displayed increased mRNA levels of mdtA, mdtB, and mdtC and an increase in MICs of tigecycline. The complemented strain of sRNA-120 restored the mRNA levels of these genes and the susceptibility to tigecycline. RNA antisense purification and parallel reaction monitoring mass spectrometry were performed to verify the interactions between sRNA-120 and mdtABC. Collectively, our study highlights that the post-transcriptional repression of mdtABC through sRNA-120 may provide an additional layer of efflux pump gene expression control, which is important for resistance and heteroresistance in clinical K. pneumoniae isolates.

替加环素和新近获得美国食品和药物管理局批准的四环素类药物(包括克拉维酸和奥马他环素)被视为治疗耐多药肠杆菌属的最后手段。然而,肺炎克雷伯菌对替加环素的耐药性有所增加,尤其是异抗性的内在机制尚不清楚。本研究旨在阐明临床肺炎克雷伯菌分离株对替加环素耐药和异耐药的机制。本研究共收集了 153 株临床肺炎克雷伯菌分离株,采用肉汤微量稀释法和群体分析图谱法分别鉴定出 15 株对替加环素耐药的分离株和 3 株对替加环素异耐药的分离株。提取了肺炎克氏菌 ATCC13883 和实验室诱导的耐替加环菌株的总 RNA,并在 Illumina 平台上进行了测序。利用定量实时 PCR 分析并验证了肺炎克雷伯菌临床分离株中的差异表达基因和调控小 RNA(sRNA)。RNA 测序结果显示,耐替加环素菌株中的 mdtABC 外排泵基因显著上调。在临床肺炎克雷伯菌分离株中观察到了 mdtABC 的过表达,这增加了替加环素的最低抑菌浓度(MICs),并参与了替加环素的异抗性。sRNA 测序分析表明,候选 sRNA-120 直接与 mdtABC 操作子相互作用,并在耐替加环素菌株中被下调。我们生成了一株 sRNA-120 缺失突变菌株和一株肺炎双球菌互补菌株。缺失 sRNA-120 的菌株显示 mdtA、mdtB 和 mdtC 的 mRNA 水平升高,对替加环素的 MICs 也升高。sRNA-120 的互补菌株恢复了这些基因的 mRNA 水平和对替加环素的敏感性。为了验证 sRNA-120 与 mdtABC 之间的相互作用,我们进行了 RNA 反义纯化和平行反应监测质谱分析。总之,我们的研究强调了通过 sRNA-120 对 mdtABC 的转录后抑制可能提供了另一层外排泵基因表达控制,这对临床肺炎克雷伯菌分离株的耐药性和异抗性非常重要。
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引用次数: 0
Sphingomonas sp. Hbc-6 alters Arabidopsis metabolites to improve plant growth and drought resistance by manipulating the microbiome 拟南芥鞘氨单胞菌 Hbc-6 通过操纵微生物组改变拟南芥代谢物,从而改善植物生长和抗旱性
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-18 DOI: 10.1016/j.micres.2024.127852
Fang Wang , Mingyue Jia , Kun Li , Yafang Cui , Lizhe An , Hongmei Sheng

Drought significantly affects crop productivity and poses a considerable threat to agricultural ecosystems. Plant growth-promoting bacteria (PGPB) and plant microbiome play important roles in improving drought resistance and plant performance. However, the response of the rhizosphere microbiota to PGPB during the development of plants and the interaction between inoculum, microbiota, and plants under drought stress remain to be explored. In the present study, we used culturomic, microbiomic, and metabonomic analyses to uncover the mechanisms by which Sphingomonas sp. Hbc-6, a PGPB, promotes Arabidopsis growth and enhances drought resistance. We found that the rhizosphere microbiome assembly was interactively influenced by developmental stage, Hbc-6, and drought; the bacterial composition exhibited three patterns of shifts with developmental stage: resilience, increase, and decrease. Drought diminished microbial diversity and richness, whereas Hbc-6 increased microbial diversity and helped plants recruit specific beneficial bacterial taxa at each developmental stage, particularly during the bolting stage. Some microorganisms enriched by Hbc-6 had the potential to promote carbon and nitrogen cycling processes, and 86.79 % of the isolated strains exhibited PGP characteristics (for example Pseudomonas sp. TA9). They jointly regulated plant physiological metabolism (i.e., upregulated drought resistant-facilitating substances and reduced harmful substances), thereby stimulating the growth of Arabidopsis and increasing plant biomass under drought stress conditions. Collectively, these results indicate that Hbc-6 mediates plant growth and drought resistance by affecting the microbiome. The study thus provides novel insights and strain resources for drought-resistant, high-yielding crop cultivation and breeding.

干旱严重影响作物产量,并对农业生态系统构成巨大威胁。植物生长促进菌(PGPB)和植物微生物群在提高抗旱性和植物表现方面发挥着重要作用。然而,植物生长过程中根瘤微生物群对 PGPB 的反应以及干旱胁迫下接种物、微生物群和植物之间的相互作用仍有待探索。在本研究中,我们利用培养物组学、微生物组学和代谢组学分析揭示了拟南芥根瘤单胞菌(Sphingomonas sp. Hbc-6)促进拟南芥生长和增强抗旱性的机制。我们发现,根瘤微生物组的组合受到发育阶段、Hbc-6和干旱的交互影响;细菌组成随着发育阶段的变化呈现出三种模式:恢复力、增加和减少。干旱降低了微生物的多样性和丰富度,而 Hbc-6 增加了微生物的多样性,并帮助植物在每个发育阶段(尤其是萌芽阶段)招募特定的有益细菌类群。Hbc-6 富集的一些微生物具有促进碳和氮循环过程的潜力,86.79% 的分离菌株表现出 PGP 特性(例如假单胞菌 TA9)。它们共同调节植物生理代谢(即上调抗旱促进物质和减少有害物质),从而在干旱胁迫条件下刺激拟南芥生长并增加植物生物量。总之,这些结果表明,Hbc-6 通过影响微生物组介导植物生长和抗旱。因此,该研究为抗旱高产作物栽培和育种提供了新的见解和菌株资源。
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引用次数: 0
Exploring the journey: A comprehensive review of vaccine development against Klebsiella pneumoniae 探索之旅:肺炎克雷伯氏菌疫苗研发综述。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-07-18 DOI: 10.1016/j.micres.2024.127837
Bruno Douradinha

Klebsiella pneumoniae, a prominent nosocomial pathogen, poses a critical global health threat due to its multidrug-resistant (MDR) and hypervirulent strains. This comprehensive review focuses into the complex approaches undertaken in the development of vaccines against K. pneumoniae. Traditional methods, such as whole-cell and ribosomal-based vaccines, are compared with modern strategies, including DNA and mRNA vaccines, and extracellular vesicles (EVs), among others. Each method presents unique advantages and challenges, emphasising the complexity of developing an effective vaccine against this pathogen. Significant advancements in computational tools and artificial intelligence (AI) have revolutionised antigen identification and vaccine design, enhancing the precision and efficiency of developing multiepitope-based vaccines. The review also highlights the potential of glycomics and immunoinformatics in identifying key antigenic components and elucidating immune evasion mechanisms employed by K. pneumoniae. Despite progress, challenges remain in ensuring the safety, efficacy, and manufacturability of these vaccines. Notably, EVs demonstrate promise due to their intrinsic adjuvant properties and ability to elicit robust immune responses, although concerns regarding inflammation and antigen variability persist. This review provides a critical overview of the current landscape of K. pneumoniae vaccine development, stressing the need for continued innovation and interdisciplinary collaboration to address this pressing public health issue. The integration of advanced computational methods and AI holds the potential to accelerate the development of effective immunotherapies, paving the way for novel vaccines against MDR K. pneumoniae.

肺炎克雷伯菌是一种常见的医院病原体,由于其具有多重耐药性(MDR)和高病毒性菌株,对全球健康构成了严重威胁。本综述重点介绍了开发肺炎克雷伯菌疫苗的复杂方法。将全细胞疫苗和基于核糖体的疫苗等传统方法与 DNA 和 mRNA 疫苗以及细胞外囊泡 (EVs) 等现代策略进行了比较。每种方法都有其独特的优势和挑战,凸显了针对这种病原体开发有效疫苗的复杂性。计算工具和人工智能(AI)的重大进步彻底改变了抗原鉴定和疫苗设计,提高了开发基于多位点的疫苗的精确性和效率。综述还强调了糖学和免疫信息学在识别关键抗原成分和阐明肺炎克雷伯菌所采用的免疫逃避机制方面的潜力。尽管取得了进展,但在确保这些疫苗的安全性、有效性和可制造性方面仍存在挑战。值得注意的是,EVs 因其固有的佐剂特性和诱导强大免疫反应的能力而大有可为,但人们对炎症和抗原变异性的担忧依然存在。本综述对肺炎克氏菌疫苗开发的现状进行了重要概述,强调了持续创新和跨学科合作的必要性,以解决这一紧迫的公共卫生问题。先进计算方法与人工智能的结合有可能加速有效免疫疗法的开发,为针对 MDR 肺炎克氏菌的新型疫苗铺平道路。
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Microbiological research
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