Nature Microbiology最新文献_第8页

Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses 肠道微生物来源的六酰化脂多糖增强癌症免疫治疗反应

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-02-10 DOI: 10.1038/s41564-025-01930-y

Puspendu Sardar, Benjamin S. Beresford-Jones, Wangmingyu Xia, Omar Shabana, Satoshi Suyama, Ruben J. F. Ramos, Amelia T. Soderholm, Panagiotis Tourlomousis, Paula Kuo, Alexander C. Evans, Charlotte J. Imianowski, Alberto G. Conti, Alexander J. Wesolowski, Natalie M. Baker, Emily A. L. McCord, Klaus Okkenhaug, Sarah K. Whiteside, Rahul Roychoudhuri, Clare E. Bryant, Justin R. Cross, Virginia A. Pedicord

{"title":"Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses","authors":"Puspendu Sardar, Benjamin S. Beresford-Jones, Wangmingyu Xia, Omar Shabana, Satoshi Suyama, Ruben J. F. Ramos, Amelia T. Soderholm, Panagiotis Tourlomousis, Paula Kuo, Alexander C. Evans, Charlotte J. Imianowski, Alberto G. Conti, Alexander J. Wesolowski, Natalie M. Baker, Emily A. L. McCord, Klaus Okkenhaug, Sarah K. Whiteside, Rahul Roychoudhuri, Clare E. Bryant, Justin R. Cross, Virginia A. Pedicord","doi":"10.1038/s41564-025-01930-y","DOIUrl":"10.1038/s41564-025-01930-y","url":null,"abstract":"The gut microbiome modulates immunotherapy treatment responses, and this may explain why immune checkpoint inhibitors, such as anti-PD-1, are only effective in some patients. Previous studies correlated lipopolysaccharide (LPS)-producing gut microbes with poorer prognosis; however, LPS from diverse bacterial species can range from immunostimulatory to inhibitory. Here, by functionally analysing faecal metagenomes from 112 patients with melanoma, we found that a subset of LPS-producing bacteria encoding immunostimulatory hexa-acylated LPS was enriched in microbiomes of clinical responders. In an implanted tumour mouse model of anti-PD-1 treatment, microbiota-derived hexa-acylated LPS was required for effective anti-tumour immune responses, and LPS-binding antibiotics and a small-molecule TLR4 antagonist abolished anti-PD-1 efficacy. Conversely, oral administration of hexa-acylated LPS to mice significantly augmented anti-PD-1-mediated anti-tumour immunity. Penta-acylated LPS did not improve anti-PD-1 efficacy in vivo and inhibited hexa-acylated LPS-induced immune activation in vitro. Microbiome hexa-acylated LPS therefore represents an accessible predictor and potential enhancer of immunotherapy responses. Hexa-acylated lipopolysaccharides from the gut microbiota are associated with efficacy in patients with cancer receiving anti-PD-1 and stimulate host immune activation for enhanced anti-tumour immunity in mouse models.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 3","pages":"795-807"},"PeriodicalIF":20.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-025-01930-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375418","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

Design and regulation of engineered bacteria for environmental release 环境释放工程细菌的设计与调控

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-02-04 DOI: 10.1038/s41564-024-01918-0

Yonatan Chemla, Connor J. Sweeney, Christopher A. Wozniak, Christopher A. Voigt

{"title":"Design and regulation of engineered bacteria for environmental release","authors":"Yonatan Chemla, Connor J. Sweeney, Christopher A. Wozniak, Christopher A. Voigt","doi":"10.1038/s41564-024-01918-0","DOIUrl":"10.1038/s41564-024-01918-0","url":null,"abstract":"Emerging products of biotechnology involve the release of living genetically modified microbes (GMMs) into the environment. However, regulatory challenges limit their use. So far, GMMs have mainly been tested in agriculture and environmental cleanup, with few approved for commercial purposes. Current government regulations do not sufficiently address modern genetic engineering and limit the potential of new applications, including living therapeutics, engineered living materials, self-healing infrastructure, anticorrosion coatings and consumer products. Here, based on 47 global studies on soil-released GMMs and laboratory microcosm experiments, we discuss the environmental behaviour of released bacteria and offer engineering strategies to help improve performance, control persistence and reduce risk. Furthermore, advanced technologies that improve GMM function and control, but lead to increases in regulatory scrutiny, are reviewed. Finally, we propose a new regulatory framework informed by recent data to maximize the benefits of GMMs and address risks. Chemla et al. review the release of bacteria into the environment and propose engineering strategies to help improve performance and reduce risk.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"281-300"},"PeriodicalIF":20.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143084096","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

Ensuring rigour of low-biomass microbiome research 确保低生物量微生物组研究的严谨性

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-02-04 DOI: 10.1038/s41564-025-01939-3

引用次数: 0

Shigella infection is facilitated by interaction of human enteric α-defensin 5 with colonic epithelial receptor P2Y11 人肠道α-防御素5与结肠上皮受体P2Y11的相互作用促进了志贺氏菌感染

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-02-03 DOI: 10.1038/s41564-024-01901-9

Dan Xu, Mengyao Guo, Xin Xu, Gan Luo, Yaxin Liu, Stephen J. Bush, Chengyao Wang, Tun Xu, Wenxin Zeng, Chongbing Liao, Qingxia Wang, Wei Zhao, Wenying Zhao, Yuezhuangnan Liu, Shanshan Li, Shuangshuang Zhao, Yaming Jiu, Nathalie Sauvonnet, Wuyuan Lu, Philippe J. Sansonetti, Kai Ye

{"title":"Shigella infection is facilitated by interaction of human enteric α-defensin 5 with colonic epithelial receptor P2Y11","authors":"Dan Xu, Mengyao Guo, Xin Xu, Gan Luo, Yaxin Liu, Stephen J. Bush, Chengyao Wang, Tun Xu, Wenxin Zeng, Chongbing Liao, Qingxia Wang, Wei Zhao, Wenying Zhao, Yuezhuangnan Liu, Shanshan Li, Shuangshuang Zhao, Yaming Jiu, Nathalie Sauvonnet, Wuyuan Lu, Philippe J. Sansonetti, Kai Ye","doi":"10.1038/s41564-024-01901-9","DOIUrl":"10.1038/s41564-024-01901-9","url":null,"abstract":"Human enteric α-defensin 5 (HD5) is an immune system peptide that acts as an important antimicrobial factor but is also known to promote pathogen infections by enhancing adhesion of the pathogens. The mechanistic basis of these conflicting functions is unknown. Here we show that HD5 induces abundant filopodial extensions in epithelial cells that capture Shigella, a major human enteroinvasive pathogen that is able to exploit these filopodia for invasion, revealing a mechanism for HD5-augmented bacterial invasion. Using multi-omics screening and in vitro, organoid, dynamic gut-on-chip and in vivo models, we identify the HD5 receptor as P2Y11, a purinergic receptor distributed apically on the luminal surface of the human colonic epithelium. Inhibitor screening identified cAMP-PKA signalling as the main pathway mediating the cytoskeleton-regulating activity of HD5. In illuminating this mechanism of Shigella invasion, our findings raise the possibility of alternative intervention strategies against HD5-augmented infections. HD5 induces filopodial extensions in epithelial cells that the pathogen Shigella exploits to facilitate invasion and infection.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"509-526"},"PeriodicalIF":20.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077191","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

SAMPL-seq reveals micron-scale spatial hubs in the human gut microbiome SAMPL-seq揭示了人类肠道微生物组中微米尺度的空间枢纽

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-02-03 DOI: 10.1038/s41564-024-01914-4

Miles Richardson, Shijie Zhao, Liyuan Lin, Ravi U. Sheth, Yiming Qu, Jeongchan Lee, Thomas Moody, Deirdre Ricaurte, Yiming Huang, Florencia Velez-Cortes, Guillaume Urtecho, Harris H. Wang

{"title":"SAMPL-seq reveals micron-scale spatial hubs in the human gut microbiome","authors":"Miles Richardson, Shijie Zhao, Liyuan Lin, Ravi U. Sheth, Yiming Qu, Jeongchan Lee, Thomas Moody, Deirdre Ricaurte, Yiming Huang, Florencia Velez-Cortes, Guillaume Urtecho, Harris H. Wang","doi":"10.1038/s41564-024-01914-4","DOIUrl":"10.1038/s41564-024-01914-4","url":null,"abstract":"The local arrangement of microbes can profoundly impact community assembly, function and stability. However, our understanding of the spatial organization of the human gut microbiome at the micron scale is limited. Here we describe a high-throughput and streamlined method called Split-And-pool Metagenomic Plot-sampling sequencing (SAMPL-seq) to capture spatial co-localization in a complex microbial consortium. The method obtains microbial composition of micron-scale subcommunities through split-and-pool barcoding. SAMPL-seq analysis of the healthy human gut microbiome identified bacterial taxa pairs that consistently co-occurred both over time and across multiple individuals. These co-localized microbes organize into spatially distinct groups or ‘spatial hubs’ dominated by Bacteroidaceae, Ruminococcaceae and Lachnospiraceae families. Using inulin as a dietary perturbation, we observed reversible spatial rearrangement of the gut microbiome where specific taxa form new local partnerships. Spatial metagenomics using SAMPL-seq can unlock insights into microbiomes at the micron scale. Split-And-pool Metagenomic Plot-sampling sequencing (SAMPL-seq) can be applied to complex microbial communities to reveal spatial co-localization of microbes at the micron scale.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"527-540"},"PeriodicalIF":20.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077192","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

Sliding clamp protein enables long-range gene silencing in a bacterial plasmid 滑动钳蛋白使细菌质粒中的远程基因沉默

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-02-03 DOI: 10.1038/s41564-025-01924-w

引用次数: 0

Genome-wide gene expression profiles throughout human malaria parasite liver stage development in humanized mice 全基因组基因表达谱在人源化小鼠中贯穿人疟疾寄生虫肝脏发育阶段

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-01-31 DOI: 10.1038/s41564-024-01905-5

Gigliola Zanghí, Hardik Patel, Jenny L. Smith, Nelly Camargo, Yeji Bae, Eva Hesping, Justin A. Boddey, Kannan Venugopal, Matthias Marti, Erika L. Flannery, Vorada Chuenchob, Matthew E. Fishbaugher, Sebastian A. Mikolajczak, Wanlapa Roobsoong, Jetsumon Sattabongkot, Priya Gupta, Lucia Pazzagli, Nastaran Rezakhani, William Betz, Kiera Hayes, Debashree Goswami, Ashley M. Vaughan, Stefan H. I. Kappe

{"title":"Genome-wide gene expression profiles throughout human malaria parasite liver stage development in humanized mice","authors":"Gigliola Zanghí, Hardik Patel, Jenny L. Smith, Nelly Camargo, Yeji Bae, Eva Hesping, Justin A. Boddey, Kannan Venugopal, Matthias Marti, Erika L. Flannery, Vorada Chuenchob, Matthew E. Fishbaugher, Sebastian A. Mikolajczak, Wanlapa Roobsoong, Jetsumon Sattabongkot, Priya Gupta, Lucia Pazzagli, Nastaran Rezakhani, William Betz, Kiera Hayes, Debashree Goswami, Ashley M. Vaughan, Stefan H. I. Kappe","doi":"10.1038/s41564-024-01905-5","DOIUrl":"10.1038/s41564-024-01905-5","url":null,"abstract":"Gene expression of Plasmodium falciparum (Pf) liver-stage (LS) parasites has remained poorly characterized, although they are major vaccine and drug targets. Using a human liver-chimaeric mouse model and a fluorescent parasite line (PfNF54CSPGFP), we isolated PfLS and performed transcriptomics on key LS developmental phases. We linked clustered gene expression to ApiAP2, a major family of transcription factors that regulate the parasite life cycle. This provided insights into transcriptional regulation of LS infection and expression of essential LS metabolic and biosynthetic pathways. We observed expression of antigenically variant PfEMP1 proteins and the major Pf protein export machine PTEX and identified protein candidates that might be exported by LS parasites. Comparing Pf and P. vivax LS transcriptomes, we uncovered differences in their expression of sexual commitment factors. This data will aid LS research and vaccine and drug target identification for prevention of malaria infection. Transcriptomics of gene expression in Plasmodium falciparum liver-stage parasites reveals transcriptional regulation, metabolic pathways and antigen expression, facilitating vaccine and drug target identification.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"569-584"},"PeriodicalIF":20.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01905-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071898","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

Author Correction: Aspergillus cvjetkovicii protects against phytopathogens through interspecies chemical signalling in the phyllosphere 作者更正：cvjetkovicii曲霉通过层状圈的种间化学信号来抵抗植物病原体

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-01-31 DOI: 10.1038/s41564-025-01942-8

Xiaoyan Fan, Haruna Matsumoto, Haorong Xu, Hongda Fang, Qianqian Pan, Tianxing Lv, Chengfang Zhan, Xiaoxiao Feng, Xiaoyu Liu, Danrui Su, Mengyuan Fan, Zhonghua Ma, Gabriele Berg, Shaojia Li, Tomislav Cernava, Mengcen Wang

引用次数: 0

Microbiota-derived succinate promotes enterohaemorrhagic Escherichia coli virulence via lysine succinylation 微生物来源的琥珀酸盐通过赖氨酸琥珀酰化促进肠出血性大肠杆菌的毒力

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-01-31 DOI: 10.1038/s41564-025-01931-x

Linxing Li, Yutao Liu, Dan Liu, Jing Wang, Min Wang, Binbin Xiang, Jingliang Qin, Ting Yao, Wanwu Li, Pan Wu, Qian Wang, Jianji Zhang, Yanli Xu, Miaomiao Liu, Yanling Wang, Guozhen Ma, Ruiying Liu, Xiaoya Li, Zimeng Huai, Yu Huang, Han Guo, Bin Yang, Lu Feng, Di Huang, Kai Zhang, Lei Wang, Bin Liu

{"title":"Microbiota-derived succinate promotes enterohaemorrhagic Escherichia coli virulence via lysine succinylation","authors":"Linxing Li, Yutao Liu, Dan Liu, Jing Wang, Min Wang, Binbin Xiang, Jingliang Qin, Ting Yao, Wanwu Li, Pan Wu, Qian Wang, Jianji Zhang, Yanli Xu, Miaomiao Liu, Yanling Wang, Guozhen Ma, Ruiying Liu, Xiaoya Li, Zimeng Huai, Yu Huang, Han Guo, Bin Yang, Lu Feng, Di Huang, Kai Zhang, Lei Wang, Bin Liu","doi":"10.1038/s41564-025-01931-x","DOIUrl":"10.1038/s41564-025-01931-x","url":null,"abstract":"Succinate upregulates enterohaemorrhagic Escherichia coli (EHEC) virulence. Lysine succinylation, a post-translational modification, regulates cellular function in eukaryotes but is less characterized in bacteria. We hypothesized that lysine succinylation regulates EHEC virulence. Here we used SILAC-based proteomics and characterized the EHEC succinylome to show that the transcription factor, PurR, is succinylated at K24 and K55. Succinylation of PurR inhibited its ability to directly bind DNA and repress expression of a major virulence factor, the Type 3 Secretion System (T3SS), thus increasing T3SS expression. Deletion of purR, or K24E or K55E mutation, increased EHEC adherence to cells and colonization of infant rabbits. Using mice treated with streptomycin to deplete succinate, or colonized with succinate-producing Prevotella copri to increase succinate levels, we showed that microbiota-derived succinate increased succinylation of PurR to promote virulence of Citrobacter rodentium, a model for EHEC, in mice. Lastly, we identified CitC as the succinyltransferase required for PurR modification. Gut microbiota-derived succinate promotes CitC succinyltransferase-dependent succinylation of PurR to alleviate T3SS repression and promote virulence in enterohaemorrhagic Escherichia coli and Citrobacter rodentium.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 3","pages":"749-764"},"PeriodicalIF":20.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071897","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

Carbohydrate-active enzymes from Akkermansia muciniphila break down mucin O-glycans to completion 来自嗜粘菌的碳水化合物活性酶将粘蛋白o -聚糖分解完成

IF 20.5 1区生物学

Nature Microbiology Pub Date : 2025-01-31 DOI: 10.1038/s41564-024-01911-7

Cassie R. Bakshani, Taiwo O. Ojuri, Bo Pilgaard, Jesper Holck, Ross McInnes, Radoslaw P. Kozak, Maria Zakhour, Sara Çakaj, Manon Kerouedan, Emily Newton, David N. Bolam, Lucy I. Crouch

{"title":"Carbohydrate-active enzymes from Akkermansia muciniphila break down mucin O-glycans to completion","authors":"Cassie R. Bakshani, Taiwo O. Ojuri, Bo Pilgaard, Jesper Holck, Ross McInnes, Radoslaw P. Kozak, Maria Zakhour, Sara Çakaj, Manon Kerouedan, Emily Newton, David N. Bolam, Lucy I. Crouch","doi":"10.1038/s41564-024-01911-7","DOIUrl":"10.1038/s41564-024-01911-7","url":null,"abstract":"Akkermansia muciniphila is a human microbial symbiont residing in the mucosal layer of the large intestine. Its main carbon source is the highly heterogeneous mucin glycoprotein, and it uses an array of carbohydrate-active enzymes and sulfatases to access this complex energy source. Here we describe the biochemical characterization of 54 glycoside hydrolases, 11 sulfatases and 1 polysaccharide lyase from A. muciniphila to provide a holistic understanding of their carbohydrate-degrading activities. This was achieved using a variety of liquid chromatography techniques, mass spectrometry, enzyme kinetics and thin-layer chromatography. These results are supported with A. muciniphila growth and whole-cell assays. We find that these enzymes can act synergistically to degrade the O-glycans on the mucin polypeptide to completion, down to the core N-acetylgalactosaime. In addition, these enzymes can break down human breast milk oligosaccharide, ganglioside and globoside glycan structures, showing their capacity to target a variety of host glycans. These data provide a resource to understand the full degradative capability of the gut microbiome member A. muciniphila. Biochemical characterization of 66 carbohydrate-active enzymes from the gut microorganism Akkermansia muciniphila reveals that these enzymes can break down a range of host glycans, including mucin, which they degrade to completion.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"585-598"},"PeriodicalIF":20.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01911-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071960","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