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Function analysis of RNase III in response to oxidative stress in Synechocystis sp. PCC 6803 胞囊藻(Synechocystis sp. pcc6803) RNase III响应氧化应激的功能分析。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2025-01-02 DOI: 10.1016/j.micres.2024.128045
Yihang Zhang , Xinyu Hu , Shanyu Wu , Tianyuan Zhang , Guidan Yang , Zhijie Li , Li Wang , Wenli Chen
RNase III, a ubiquitously distributed endonuclease, plays an important role in RNA processing and functions as a global regulator of gene expression. In this study, we explored the role of RNase III in mediating the oxidative stress response in Synechocystis sp. PCC 6803. Phenotypic analysis demonstrated that among the three RNase III-encoding genes (slr0346, slr1646, and slr0954), the deletional mutation of slr0346 significantly impaired the growth of cyanobacteria on BG11 agar plates. However, this growth effect was not observed in liquid culture. In contrast, the deletion of slr1646 and slr0954 did not affect the growth of cyanobacteria under the tested conditions. However, under methyl viologen (MV)-induced oxidative stress, the slr0346 deletion mutant exhibited a slower growth rate compared to the wild-type strain. Transcriptome analysis revealed that five pathways—nitrogen metabolism, ABC transporters, folate biosynthesis, ribosome biogenesis, and oxidative phosphorylation—were implicated in the oxidative stress response. The slr0346 gene suppressed global gene expression, with a particular impact on genes associated with energy metabolism, protein synthesis, and transport. Furthermore, we identified Ssl3432 as an interacting protein that may participate in the oxidative stress response in coordination with Slr0346. Overall, the deletion of slr0346 markedly weakened the ability of Synechocystis sp. PCC 6803 to respond to MV-induced oxidative stress. This study offers valuable insights into the oxidative stress response of Synechocystis sp. PCC 6803 and highlights the role of RNase III in adapting to environmental stress.
RNase III是一种普遍存在的内切酶,在RNA加工过程中起着重要作用,是基因表达的全局调节剂。在本研究中,我们探讨了RNase III在胞囊藻(Synechocystis sp. PCC 6803)氧化应激反应中的作用。表型分析表明,在3个RNase iii编码基因(slr0346、slr1646和slr0954)中,slr0346缺失突变显著抑制了蓝藻在BG11琼脂板上的生长。然而,在液体培养中没有观察到这种生长效应。相比之下,slr1646和slr0954的缺失在测试条件下不影响蓝藻的生长。然而,在甲基紫素(MV)诱导的氧化应激下,slr0346缺失突变体的生长速度比野生型菌株慢。转录组分析显示,氮代谢、ABC转运蛋白、叶酸生物合成、核糖体生物发生和氧化磷酸化这五种途径与氧化应激反应有关。slr0346基因抑制全局基因表达,对与能量代谢、蛋白质合成和运输相关的基因有特别的影响。此外,我们发现Ssl3432是一种相互作用蛋白,可能与Slr0346协同参与氧化应激反应。总之,slr0346的缺失显著削弱了Synechocystis sp. PCC 6803对mv诱导的氧化应激的响应能力。本研究为Synechocystis sp. PCC 6803的氧化应激反应提供了有价值的见解,并突出了RNase III在适应环境应激中的作用。
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引用次数: 0
Bridging dietary polysaccharides and gut microbiome: How to achieve precision modulation for gut health promotion 桥接膳食多糖和肠道微生物群:如何实现肠道健康促进的精确调节。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2025-01-02 DOI: 10.1016/j.micres.2025.128046
Xihao Sun , Zhangming Pei , Hongchao Wang , Jianxin Zhao , Wei Chen , Wenwei Lu
Dietary polysaccharides function not only as indispensable nutrients and energy sources for the host organism but also as critical substrates for the gut microbiota. Gut microorganisms possess the ability to selectively degrade and metabolize specific dietary polysaccharides, thus fostering their proliferation and yielding crucial bioactive metabolites that potentially influence host metabolic and immune pathways. Dysbiosis of the gut microbiota has been extensively documented to be closely linked with the onset and progression of various diseases; in this regard, the precision modulation strategy of the gut microbiome via dietary polysaccharides holds substantial potential to enhance human health. Here, we delve into the therapeutic potential of dietary polysaccharides for the precision modulation of specific gut microorganisms via dietary interventions, with particular emphasis on their implications for the prevention and management of metabolic and inflammatory disorders. Given the complexity of the human gut microbiome and the varying degrees to which different bacterial members utilize carbohydrates, we conduct an in-depth analysis of the differential utilization of dietary polysaccharides by key gut microbiome, with particular emphasis on the role of carbohydrate-active enzymes in these processes. Furthermore, we elucidate the pivotal role of carbohydrate utilization within microbial cross-feeding networks and its significance in maintaining gut homeostasis. In summary, this review investigates the precision modulation of gut microbiota through dietary polysaccharides, with the aim of establishing a theoretical foundation for the development of personalized nutritional interventions. These strategies hold substantial potential for enhancing human health and offer valuable opportunities for the prevention and treatment of microbiota-associated diseases.
饲粮多糖不仅是宿主不可缺少的营养物质和能量来源,而且是肠道微生物群的关键底物。肠道微生物具有选择性降解和代谢特定膳食多糖的能力,从而促进其增殖并产生关键的生物活性代谢物,这些代谢物可能影响宿主的代谢和免疫途径。肠道菌群的生态失调已被广泛记录,与各种疾病的发生和进展密切相关;在这方面,通过膳食多糖对肠道微生物群进行精确调节的策略具有增强人类健康的巨大潜力。在这里,我们深入研究了膳食多糖通过饮食干预精确调节特定肠道微生物的治疗潜力,特别强调了它们对预防和管理代谢和炎症性疾病的影响。鉴于人类肠道微生物组的复杂性和不同细菌成员利用碳水化合物的不同程度,我们深入分析了关键肠道微生物组对膳食多糖的差异利用,特别强调了碳水化合物活性酶在这些过程中的作用。此外,我们阐明了碳水化合物利用在微生物交叉摄食网络中的关键作用及其在维持肠道稳态中的意义。综上所述,本文综述了膳食多糖对肠道菌群的精确调节,旨在为个性化营养干预的发展奠定理论基础。这些战略在增进人类健康方面具有巨大潜力,并为预防和治疗微生物群相关疾病提供了宝贵的机会。
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引用次数: 0
Seasonal dynamics of kiwifruit microbiome: A case study in a KVDS-affected orchard 猕猴桃微生物群落的季节动态:以受kvds影响的果园为例。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.micres.2024.128044
Antonella Cardacino, Silvia Turco, Giorgio Mariano Balestra
Over the past decade, Italian kiwifruit orchards and overall production have faced a significant threat from Kiwifruit Vine Decline Syndrome (KVDS). Despite the insights gained from metagenomics studies into the microbial communities associated with the disease, unanswered questions still remain. In this study, the evolution of bacterial, fungal, and oomycetes communities in soil and root endosphere at three different time points during the vegetative season was investigated for the first time in a KVDS-affected orchard in the Lazio Region. The fungal and oomycetes genera previously associated with the syndrome, including Fusarium, Ilyonectria, Thelonectria, Phytophthora, Pythium and Globisporangium, were identified in both groups. In contrast, the characterization of bacterial communities revealed the first instance of the presence of the genus Ralstonia in soil and root samples. The microbiome composition shifts between KVDS-affected and asymptomatic plants were significant as evidenced by the results, particularly after a temperature increase. This temperature change coincided with the onset of severe disease symptoms and may indicate a key role in the progression of KVDS.
在过去的十年里,意大利的猕猴桃果园和整体生产都面临着猕猴桃蔓衰综合征(KVDS)的严重威胁。尽管从宏基因组学研究中获得了与该疾病相关的微生物群落的见解,但仍存在未解决的问题。本研究首次在拉齐奥地区一个受kvds影响的果园中,研究了营养季节三个不同时间点土壤和根内圈细菌、真菌和卵菌群落的演变。在两组中均发现了以前与该综合征相关的真菌属和卵菌属,包括镰刀菌、Ilyonectria、Thelonectria、Phytophthora、Pythium和Globisporangium。相比之下,细菌群落的特征揭示了在土壤和根样品中首次存在Ralstonia属。结果表明,受kvds影响和无症状植物之间的微生物组组成变化显著,特别是在温度升高后。这种温度变化与严重疾病症状的发生一致,可能表明在KVDS的进展中起关键作用。
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引用次数: 0
Sorghum rhizosphere bacteriome studies and generation of multistrain beneficial bacterial consortia 高粱根际细菌组研究及多菌种有益菌群的产生。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-12-27 DOI: 10.1016/j.micres.2024.128036
Chandan Kumar , Alfonso Esposito , Iris Bertani , Samson Musonerimana , Mulissa Jida Midekssa , Kassahun Tesfaye , Devin Coleman Derr , Lara Donaldson , Silvano Piazza , Cristina Bez , Vittorio Venturi
The plant rhizosphere microbiome plays a crucial role in plant growth and health. Within this microbiome, bacteria dominate, exhibiting traits that benefit plants, such as facilitating nutrient acquisition, fixing nitrogen, controlling pathogens, and promoting root growth. This study focuses on designing synthetic bacterial consortia using key bacterial strains which have been mapped and then isolated from the sorghum rhizosphere microbiome. A large set of samples of the rhizosphere bacteriome of Sorghum bicolor was generated and analyzed across various genotypes and geographical locations. We assessed the taxonomic composition and structure of the sorghum root-associated bacterial community identifying the most prevalent and keystone taxa. A set of 321 bacterial strains was then isolated, and three multi-strain consortia were designed making use of the bacteriome data generated using culture independent methodology. Subsequently, co-existence and plant-growth promoting ability of three bacterial consortia were tested both in vitro and in planta. Consortia 3 promoted plant growth in growth-chamber conditions while Consortia 1 and 2 performed better in field-plot experiments. Despite these differences, bacterial community profiling confirmed the colonization of the inoculated consortia in the sorghum rhizosphere without significant alterations to the overall bacterial community compared to the non inoculated ones. In summary, this study focused on a method, using root bacteriome data, to design and test bacterial consortia for plant beneficial effects with the aim of translating microbiome knowledge into applications.
植物根际微生物群在植物生长和健康中起着至关重要的作用。在这个微生物群中,细菌占主导地位,表现出有利于植物的特性,如促进营养获取、固定氮、控制病原体和促进根系生长。本研究的重点是利用已定位并从高粱根际微生物群中分离出来的关键菌株设计合成菌群。对不同基因型和地理位置的双色高粱根际菌群进行了大量的分析。我们对高粱根系相关细菌群落的组成和结构进行了分析,确定了最普遍和最重要的分类群。然后分离出321株细菌,利用培养独立法生成的细菌组数据设计了3个多菌株联合体。随后,在离体和植物中测试了三种细菌群落的共存和促进植物生长的能力。财团3在生长室条件下促进植株生长,财团1和财团2在大田试验中表现较好。尽管存在这些差异,但细菌群落分析证实了接种菌群在高粱根际的定植,与未接种菌群相比,总体细菌群落没有显著变化。总之,本研究的重点是一种方法,利用根细菌组数据,设计和测试细菌联合体对植物有益的影响,目的是将微生物组知识转化为应用。
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引用次数: 0
Gut microbial metabolites: The bridge connecting diet and atherosclerosis, and next-generation targets for dietary interventions 肠道微生物代谢物:连接饮食和动脉粥样硬化的桥梁,以及饮食干预的下一代目标。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-12-26 DOI: 10.1016/j.micres.2024.128037
Liyin Zhang, Yao Yin, Si Jin
Mounting evidence indicates that gut microbial metabolites are central hubs linking the gut microbiota to atherosclerosis (AS). Gut microbiota enriched with pathobiont bacteria responsible for producing metabolites like trimethylamine N-oxide and phenylacetylglutamine are related to an increased risk of cardiovascular events. Furthermore, gut microbiota enriched with bacteria responsible for producing short-chain fatty acids, indole, and its derivatives, such as indole-3-propionic acid, have demonstrated AS-protective effects. This study described AS-related gut microbial composition and how microbial metabolites affect AS. Summary findings revealed gut microbiota and their metabolites-targeted diets could benefit AS treatment. In conclusion, dietary interventions centered on the gut microbiota represent a promising strategy for AS treatment, and understanding diet-microbiota interactions could potentially be devoted to developing novel anti-AS therapies.
越来越多的证据表明,肠道微生物代谢物是连接肠道微生物群与动脉粥样硬化(AS)的中心枢纽。富含致病细菌的肠道微生物群负责产生代谢物,如三甲胺n -氧化物和苯乙酰谷氨酰胺,这与心血管事件的风险增加有关。此外,富含产生短链脂肪酸、吲哚及其衍生物(如吲哚-3-丙酸)的细菌的肠道微生物群已证明具有as保护作用。本研究描述了与AS相关的肠道微生物组成以及微生物代谢物如何影响AS。总结研究结果表明,肠道微生物群及其代谢物靶向饮食可能有益于AS治疗。总之,以肠道微生物群为中心的饮食干预是一种很有前途的AS治疗策略,了解饮食-微生物群的相互作用可能有助于开发新的抗AS治疗方法。
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引用次数: 0
Assessing the risk of TB progression: Advances in blood-based biomarker research 评估结核病进展风险:基于血液的生物标志物研究进展。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-12-26 DOI: 10.1016/j.micres.2024.128038
Zhaodong Li , Yunlong Hu , Fa Zou , Wei Gao , SiWan Feng , Guanghuan Chen , Jing Yang , Wenfei Wang , Chenyan Shi , Yi Cai , Guofang Deng , Xinchun Chen
This review addresses the significant advancements in the identification of blood-based prognostic biomarkers for tuberculosis (TB), highlighting the importance of early detection to prevent disease progression. The manuscript discusses various biomarker categories, including transcriptomic, proteomic, metabolomic, immune cell-based, cytokine-based, and antibody response-based markers, emphasizing their potential in predicting TB incidence. Despite promising results, practical application is hindered by high costs, technical complexities, and the need for extensive validation across diverse populations. Transcriptomic biomarkers, such as the Risk16 signature, show high sensitivity and specificity, while proteomic and metabolic markers provide insights into protein-level changes and biochemical alterations linked to TB. Immune cell and cytokine markers offer real-time data on the body's response to infection. The manuscript also explores the role of single-nucleotide polymorphisms in TB susceptibility and the challenges of implementing novel RNA signatures as point-of-care tests in low-resource settings. The review concludes that, while significant progress has been made, further research and development are necessary to refine these biomarkers, improve their practical application, and achieve the World Health Organization's TB elimination goals.
本文综述了在结核病(TB)血液预后生物标志物鉴定方面取得的重大进展,强调了早期检测对预防疾病进展的重要性。该手稿讨论了各种生物标志物类别,包括转录组学、蛋白质组学、代谢组学、基于免疫细胞、基于细胞因子和基于抗体反应的标志物,强调了它们在预测结核病发病率方面的潜力。尽管结果很有希望,但实际应用受到高成本、技术复杂性和需要在不同人群中进行广泛验证的阻碍。转录组生物标记,如Risk16标记,显示出高度的敏感性和特异性,而蛋白质组学和代谢标记提供了与结核病相关的蛋白质水平变化和生化改变的见解。免疫细胞和细胞因子标记提供人体对感染反应的实时数据。该手稿还探讨了单核苷酸多态性在结核病易感性中的作用,以及在低资源环境中实施新型RNA标记作为即时检测的挑战。这篇综述的结论是,虽然已经取得了重大进展,但需要进一步的研究和开发来完善这些生物标志物,改进它们的实际应用,并实现世界卫生组织消除结核病的目标。
{"title":"Assessing the risk of TB progression: Advances in blood-based biomarker research","authors":"Zhaodong Li ,&nbsp;Yunlong Hu ,&nbsp;Fa Zou ,&nbsp;Wei Gao ,&nbsp;SiWan Feng ,&nbsp;Guanghuan Chen ,&nbsp;Jing Yang ,&nbsp;Wenfei Wang ,&nbsp;Chenyan Shi ,&nbsp;Yi Cai ,&nbsp;Guofang Deng ,&nbsp;Xinchun Chen","doi":"10.1016/j.micres.2024.128038","DOIUrl":"10.1016/j.micres.2024.128038","url":null,"abstract":"<div><div>This review addresses the significant advancements in the identification of blood-based prognostic biomarkers for tuberculosis (TB), highlighting the importance of early detection to prevent disease progression. The manuscript discusses various biomarker categories, including transcriptomic, proteomic, metabolomic, immune cell-based, cytokine-based, and antibody response-based markers, emphasizing their potential in predicting TB incidence. Despite promising results, practical application is hindered by high costs, technical complexities, and the need for extensive validation across diverse populations. Transcriptomic biomarkers, such as the Risk16 signature, show high sensitivity and specificity, while proteomic and metabolic markers provide insights into protein-level changes and biochemical alterations linked to TB. Immune cell and cytokine markers offer real-time data on the body's response to infection. The manuscript also explores the role of single-nucleotide polymorphisms in TB susceptibility and the challenges of implementing novel RNA signatures as point-of-care tests in low-resource settings. The review concludes that, while significant progress has been made, further research and development are necessary to refine these biomarkers, improve their practical application, and achieve the World Health Organization's TB elimination goals.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"292 ","pages":"Article 128038"},"PeriodicalIF":6.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927293","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
Klebsiella pneumoniae ST258 impairs intracellular elastase mobilization and persists within human neutrophils
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-12-26 DOI: 10.1016/j.micres.2024.128035
Federico Birnberg-Weiss , Joselyn E. Castro , Jose R. Pittaluga , Luis A. Castillo , Daiana Martire-Greco , Federico Fuentes , Fabiana Bigi , Sonia A. Gómez , Verónica I. Landoni , Gabriela C. Fernández
Klebsiella pneumoniae (Kp) strains of sequence type (ST) 258 producing K. pneumoniae-carbapenemase (KPC) are a major cause of hospital-associated outbreaks and the main contributors of carbapenemase spreading. Here, we deepen into the mechanisms behind the inhibition of neutrophil bactericidal functions mediated by a clinical isolate of Kp ST258 KPC, Kp from now on. We found that NETs formation induced by different stimuli (PMA, ionomycin, Staphylococcus aureus) was significantly reduced in the presence of Kp. We revealed that Kp affects actin polymerization which correlates with impaired mobilization of elastase from azurophilic granules to the nucleus and reduced elastase mobilization towards phagosomes that contain bacteria. In line with these results, Kp survived within neutrophils for 3 h post-challenge without compromising neutrophil viability. We also found that different Kp clinical isolates inhibited NETs formation and actin polymerization. These results describe a strategy of evasion used by Kp to subvert PMN-mediating both intra and extracellular mechanisms of killing, representing a clear advantage for the survival and spreading of this multidrug-resistant bacteria.
{"title":"Klebsiella pneumoniae ST258 impairs intracellular elastase mobilization and persists within human neutrophils","authors":"Federico Birnberg-Weiss ,&nbsp;Joselyn E. Castro ,&nbsp;Jose R. Pittaluga ,&nbsp;Luis A. Castillo ,&nbsp;Daiana Martire-Greco ,&nbsp;Federico Fuentes ,&nbsp;Fabiana Bigi ,&nbsp;Sonia A. Gómez ,&nbsp;Verónica I. Landoni ,&nbsp;Gabriela C. Fernández","doi":"10.1016/j.micres.2024.128035","DOIUrl":"10.1016/j.micres.2024.128035","url":null,"abstract":"<div><div><em>Klebsiella pneumoniae</em> (Kp) strains of sequence type (ST) 258 producing <em>K. pneumoniae</em>-carbapenemase (KPC) are a major cause of hospital-associated outbreaks and the main contributors of carbapenemase spreading. Here, we deepen into the mechanisms behind the inhibition of neutrophil bactericidal functions mediated by a clinical isolate of Kp ST258 KPC, Kp from now on. We found that NETs formation induced by different stimuli (PMA, ionomycin, <em>Staphylococcus aureus</em>) was significantly reduced in the presence of Kp. We revealed that Kp affects actin polymerization which correlates with impaired mobilization of elastase from azurophilic granules to the nucleus and reduced elastase mobilization towards phagosomes that contain bacteria. In line with these results, Kp survived within neutrophils for 3 h post-challenge without compromising neutrophil viability. We also found that different Kp clinical isolates inhibited NETs formation and actin polymerization. These results describe a strategy of evasion used by Kp to subvert PMN-mediating both intra and extracellular mechanisms of killing, representing a clear advantage for the survival and spreading of this multidrug-resistant bacteria.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"292 ","pages":"Article 128035"},"PeriodicalIF":6.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143101082","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
The Actinobacillus pleuropneumoniae apxIV operon encodes an antibacterial toxin-immunity pair 胸膜肺炎放线杆菌apxIV操纵子编码抗菌毒素免疫对。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-12-26 DOI: 10.1016/j.micres.2024.128043
Eva Slivenecka, David Jurnecka, Jana Holubova, Ondrej Stanek, Ludmila Brazdilova, Monika Cizkova, Ladislav Bumba
The ApxIVA protein belongs to a distinct class of a “clip and link” activity of Repeat-in-ToXin (RTX) exoproteins. Along with the three other pore-forming RTX toxins (ApxI, ApxII and ApxIII), ApxIVA serves as a major virulence factor of Actinobacillus pleuropneumoniae, the causative agent of porcine pneumonia. The gene encoding ApxIVA is located on a bicistronic operon downstream of the orf1 gene and is expressed exclusively under in vivo conditions. Both ApxIVA and ORF1 are essential for full virulence of A. pleuropneumoniae, but the molecular mechanisms by which they contribute to the pathogenicity are not yet understood. Here, we provide a comprehensive structural and functional analysis of ApxIVA and ORF1 proteins. Our findings reveal that the N-terminal segment of ApxIVA shares structural similarity with colicin M (ColM)-like bacteriocins and exhibits an antimicrobial activity. The ORF1 protein resembles the colicin M immunity protein (Cmi) and, like Cmi, is exported to the periplasm through its N-terminal signal peptide. Additionally, ORF1 can protect bacterial cells from the antimicrobial activity of ApxIVA, suggesting that ORF1 and ApxIVA function as an antibacterial toxin-immunity pair. Moreover, we demonstrate that fetal bovine serum could elicit ApxIVA and ORF1 production under in vitro conditions. These findings highlight the coordinated action of various RTX determinants, where the fine-tuned spatiotemporal production of ApxIVA may enhance the fitness of A. pleuropneumoniae, facilitating its invasion to a resident microbial community on the surface of airway mucosa.
ApxIVA蛋白属于一类具有“剪切和链接”活性的重复毒素(RTX)外显蛋白。与其他三种形成孔的RTX毒素(ApxI, ApxII和ApxIII)一起,ApxIVA是猪肺炎的病原体胸膜肺炎放线杆菌的主要毒力因子。编码ApxIVA的基因位于orf1基因下游的双电子操纵子上,在体内条件下只表达。ApxIVA和ORF1对于胸膜肺炎假体的完全毒力都是必不可少的,但它们促进致病性的分子机制尚不清楚。在这里,我们对ApxIVA和ORF1蛋白进行了全面的结构和功能分析。我们的研究结果表明,ApxIVA的n端片段与colicin M (ColM)样细菌素具有结构相似性,并表现出抗菌活性。ORF1蛋白类似于colicin M免疫蛋白(Cmi),与Cmi一样,通过其n端信号肽输出到外周质。此外,ORF1可以保护细菌细胞免受ApxIVA的抗菌活性,这表明ORF1和ApxIVA是一个抗菌毒素免疫对。此外,我们证明了胎牛血清可以在体外条件下诱导ApxIVA和ORF1的产生。这些发现强调了各种RTX决定因素的协同作用,其中ApxIVA的精细时空产生可能增强胸膜肺炎单胞菌的适应度,促进其入侵气道粘膜表面的常驻微生物群落。
{"title":"The Actinobacillus pleuropneumoniae apxIV operon encodes an antibacterial toxin-immunity pair","authors":"Eva Slivenecka,&nbsp;David Jurnecka,&nbsp;Jana Holubova,&nbsp;Ondrej Stanek,&nbsp;Ludmila Brazdilova,&nbsp;Monika Cizkova,&nbsp;Ladislav Bumba","doi":"10.1016/j.micres.2024.128043","DOIUrl":"10.1016/j.micres.2024.128043","url":null,"abstract":"<div><div>The ApxIVA protein belongs to a distinct class of a “clip and link” activity of Repeat-in-ToXin (RTX) exoproteins. Along with the three other pore-forming RTX toxins (ApxI, ApxII and ApxIII), ApxIVA serves as a major virulence factor of <em>Actinobacillus pleuropneumoniae</em>, the causative agent of porcine pneumonia. The gene encoding ApxIVA is located on a bicistronic operon downstream of the <em>orf1</em> gene and is expressed exclusively under <em>in vivo</em> conditions. Both ApxIVA and ORF1 are essential for full virulence of <em>A. pleuropneumoniae</em>, but the molecular mechanisms by which they contribute to the pathogenicity are not yet understood. Here, we provide a comprehensive structural and functional analysis of ApxIVA and ORF1 proteins. Our findings reveal that the N-terminal segment of ApxIVA shares structural similarity with colicin M (ColM)-like bacteriocins and exhibits an antimicrobial activity. The ORF1 protein resembles the colicin M immunity protein (Cmi) and, like Cmi, is exported to the periplasm through its N-terminal signal peptide. Additionally, ORF1 can protect bacterial cells from the antimicrobial activity of ApxIVA, suggesting that ORF1 and ApxIVA function as an antibacterial toxin-immunity pair. Moreover, we demonstrate that fetal bovine serum could elicit ApxIVA and ORF1 production under <em>in vitro</em> conditions. These findings highlight the coordinated action of various RTX determinants, where the fine-tuned spatiotemporal production of ApxIVA may enhance the fitness of <em>A. pleuropneumoniae,</em> facilitating its invasion to a resident microbial community on the surface of airway mucosa.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"292 ","pages":"Article 128043"},"PeriodicalIF":6.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Temperate bacteriophage SapYZUs7 alters Staphylococcus aureus fitness balance by regulating expression of phage resistance, virulence and antimicrobial resistance gene 温带噬菌体SapYZUs7通过调控噬菌体耐药性、毒力和耐药基因的表达改变金黄色葡萄球菌的适应性平衡。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-12-26 DOI: 10.1016/j.micres.2024.128040
Wenyuan Zhou , Yajie Li , Yuhong Wu , Weicheng Hu , Wenjuan Li , Aiping Deng , Yeling Han , Guoqiang Zhu , Zhenquan Yang
Temperate bacteriophages are crucial for maintaining the pathogenicity and fitness of S. aureus, which also show promise as a biocontrol agent for S. aureus. However, the fitness benefit and cost of lysogeny by S. aureus temperate phages and their underlying mechanisms remain unexplored. In this study, phage resistance, virulence, antimicrobial resistance (AMR), transcriptome, and metabolome of phage SapYZUs7 lysogenic and non-lysogenic S. aureus strains were compared. Whole-genome analysis revealed that SapYZUs7 harbouring smaII associated with a single-protein MazF-like antiphage system could be integrated into the genome of S. aureus isolates. Notably, lysogenic S. aureus exhibited higher phage resistance, a lower growth rate, and inhibited metabolic activity compared to the parental strains, indicating interference of phage reproduction by smaII. Moreover, prophages carrying smaII are widely distributed across S. aureus and harboured other virulence factor (VF) and AMR genes. Besides, the SapYZUs7-integration increased phagocytosis resistance but decreased adhesion, biofilm formation, and AMR. The combined use of SapYZUs7 and antibiotics exhibited a better bactericidal effect than SapYZUs7 or the antibiotics alone. Consistently, integrated omics analysis suggested that SapYZUs7-lysogeny downregulated multiple VF and AMR genes. Our analysis suggests that SmaII drives mutualistic phage-host interactions through lysogenic conversion. The fitness cost of SapYZUs7-integration is the downregulated expression of VF and AMR genes, serving as an alternative candidate as a biocontrol agent for methicillin-resistant S. aureus and multidrug-resistant S. aureus.
温和噬菌体对维持金黄色葡萄球菌的致病性和适应性至关重要,也显示出作为金黄色葡萄球菌生物防治剂的前景。然而,金黄色葡萄球菌温带噬菌体溶原性的适应性效益和成本及其潜在机制仍未被探索。本研究比较了噬菌体SapYZUs7溶原性和非溶原性金黄色葡萄球菌菌株的噬菌体耐药性、毒力、抗菌素耐药性(AMR)、转录组和代谢组。全基因组分析显示,SapYZUs7携带与单蛋白mazf样噬菌体系统相关的smaII,可以整合到金黄色葡萄球菌分离物的基因组中。值得注意的是,与亲本菌株相比,溶原性金黄色葡萄球菌表现出更高的噬菌体抗性,更低的生长速度,并抑制代谢活性,这表明smaII干扰了噬菌体的繁殖。此外,携带smaII的噬菌体广泛分布在金黄色葡萄球菌中,并含有其他毒力因子(VF)和AMR基因。此外,sapyzus7整合体增加了吞噬抗性,但降低了粘附、生物膜形成和AMR。SapYZUs7与抗生素联合使用的杀菌效果优于SapYZUs7或抗生素单独使用。整合组学分析一致表明,SapYZUs7-lysogeny下调了多个VF和AMR基因。我们的分析表明,SmaII通过溶原性转化驱动噬菌体-宿主相互作用。sapyzus7整合的适应度代价是下调VF和AMR基因的表达,作为耐甲氧西林金黄色葡萄球菌和耐多药金黄色葡萄球菌的生物防治候选药物。
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引用次数: 0
Stealth in non-tuberculous mycobacteria: clever challengers to the immune system 非结核分枝杆菌的隐身性:免疫系统的聪明挑战者。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-12-25 DOI: 10.1016/j.micres.2024.128039
Zhenghao Wang , Xiurong Sun , Yuli Lin , Yurong Fu , Zhengjun Yi
Non-tuberculous Mycobacteria (NTM) are found extensively in various environments, yet most are non-pathogenic. Only a limited number of these organisms can cause various infections, including those affecting the lungs, skin, and central nervous system, particularly when the host's autoimmune function is compromised. Among these, Non-tuberculous Mycobacteria Pulmonary Diseases (NTM-PD) are the most prevalent. Currently, there is a lack of effective treatments and preventive measures for NTM infections. This article aims to deepen the comprehension of the pathogenic mechanisms linked to NTM and to formulate new intervention strategies by synthesizing current research and detailing the different tactics used by NTM to avoid elimination by the host's immune response. These intricate mechanisms not only affect the innate immune response but also successfully oppose the adaptive immune response, establishing persistent infections within the host. This includes effects on the functions of macrophages, neutrophils, dendritic cells, and T lymphocytes, as well as modulation of cytokine production. The article particularly emphasizes the survival strategies of NTM within macrophages, such as inhibiting phagosome maturation and acidification, resisting intracellular killing mechanisms, and interfering with autophagy and cell death pathways. This review aims to deepen the understanding of NTM's immune evasion mechanisms, thereby facilitating efforts to inhibit its proliferation and spread within the host, ultimately providing new methods and strategies for NTM-related treatments.
非结核分枝杆菌(NTM)广泛存在于各种环境中,但大多数是非致病性的。只有有限数量的这些微生物可以引起各种感染,包括那些影响肺部、皮肤和中枢神经系统的感染,特别是当宿主的自身免疫功能受损时。其中,非结核性分枝杆菌肺病(NTM-PD)最为普遍。目前,对NTM感染缺乏有效的治疗和预防措施。本文旨在通过综合现有研究,详细介绍NTM避免被宿主免疫应答消除的不同策略,加深对NTM相关致病机制的理解,并制定新的干预策略。这些复杂的机制不仅影响先天免疫反应,而且成功地对抗适应性免疫反应,在宿主体内建立持续感染。这包括对巨噬细胞、中性粒细胞、树突状细胞和T淋巴细胞功能的影响,以及对细胞因子产生的调节。文章特别强调了NTM在巨噬细胞内的生存策略,如抑制吞噬体成熟和酸化、抵抗细胞内杀伤机制、干扰自噬和细胞死亡途径等。本综述旨在加深对NTM免疫逃避机制的理解,从而促进抑制NTM在宿主内的增殖和扩散,最终为NTM相关治疗提供新的方法和策略。
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引用次数: 0
期刊
Microbiological research
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