Nature Microbiology最新文献_第10页

Peptidoglycan–outer membrane attachment generates periplasmic pressure to prevent lysis in Gram-negative bacteria 在革兰氏阴性菌中，肽聚糖-外膜附着产生质周压力以防止裂解

IF 19.4 1区生物学

Nature Microbiology Pub Date : 2025-07-29 DOI: 10.1038/s41564-025-02058-9

Michaël Deghelt, Seung-Hyun Cho, Jiawei Sun, Sander K. Govers, Arne Janssens, Alix Vincent Dachsbeck, Han K. Remaut, Kerwyn Casey Huang, Jean-François Collet

{"title":"Peptidoglycan–outer membrane attachment generates periplasmic pressure to prevent lysis in Gram-negative bacteria","authors":"Michaël Deghelt, Seung-Hyun Cho, Jiawei Sun, Sander K. Govers, Arne Janssens, Alix Vincent Dachsbeck, Han K. Remaut, Kerwyn Casey Huang, Jean-François Collet","doi":"10.1038/s41564-025-02058-9","DOIUrl":"10.1038/s41564-025-02058-9","url":null,"abstract":"Bacteria are subject to a substantial concentration differential of osmolytes between the interior and exterior of the cell, resulting in turgor pressure. Failure to mechanically balance this turgor pressure causes cells to burst. Here, using microfluidics, imaging, biochemistry and mathematical modelling, we analysed how Escherichia coli cells with structural mutations in the envelope respond to hypoosmotic shocks. We show that the peptidoglycan cell wall forms a mechanical unit with the outer membrane that limits periplasmic volume increase under hypoosmotic shock, allowing osmotic pressure build-up in the periplasm. In turn, this periplasmic pressure balances cytoplasmic turgor across the inner membrane, preventing cell lysis and death. Thus, while the peptidoglycan layer is necessary, it is not sufficient to maintain turgor and protect cells from lysis. We propose a model in which the entire cell envelope, including the periplasm, collectively enables Gram-negative bacteria to overcome osmotic challenges. Outer membrane attachment to peptidoglycan enables periplasmic pressure to build up and counter cytoplasmic turgor pressure, preventing lysis during osmotic challenges in Escherichia coli.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"1963-1974"},"PeriodicalIF":19.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719702","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

Challenges and opportunities in mRNA vaccine development against bacteria 细菌mRNA疫苗开发的挑战和机遇

IF 19.4 1区生物学

Nature Microbiology Pub Date : 2025-07-29 DOI: 10.1038/s41564-025-02070-z

Ilke Aernout, Rein Verbeke, Fabien Thery, Patrick Willems, Uri Elia, Stefaan C. De Smedt, Rino Rappuoli, Dan Peer, Francis Impens, Ine Lentacker

{"title":"Challenges and opportunities in mRNA vaccine development against bacteria","authors":"Ilke Aernout, Rein Verbeke, Fabien Thery, Patrick Willems, Uri Elia, Stefaan C. De Smedt, Rino Rappuoli, Dan Peer, Francis Impens, Ine Lentacker","doi":"10.1038/s41564-025-02070-z","DOIUrl":"10.1038/s41564-025-02070-z","url":null,"abstract":"The global surge in antimicrobial resistance presents a critical threat to public health, emphasizing the urgent need for the development of new and more effective bacterial vaccines. Since the success of mRNA vaccines during the COVID-19 pandemic, this vaccine strategy has rapidly advanced, with most efforts focused on cancer immunotherapy and targeting viral pathogens. Recently, mRNA vaccines have entered the early phases of clinical development for bacterial diseases. However, bacteria present greater biological complexity compared with viruses, posing additional challenges for vaccine design, such as antigen selection, immune response and mRNA construct design. Here, we discuss critical aspects in the development of bacterial mRNA vaccines, from antigen selection to construct design. We also highlight the current preclinical landscape and discuss remaining translational challenges and future potential for mRNA vaccines against bacterial infections. This Review reflects on the major challenges in bacterial mRNA vaccine design, provides strategies for tailoring mRNA construct design to promote humoral or cellular immunity, and provides an overview of the translational landscape for mRNA vaccines.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"1816-1828"},"PeriodicalIF":19.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719703","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

Evolution of antifungal resistance in the environment 环境中抗真菌耐药性的进化

IF 19.4 1区生物学

Nature Microbiology Pub Date : 2025-07-29 DOI: 10.1038/s41564-025-02055-y

Norman van Rhijn, Johanna Rhodes

引用次数: 0

Remote control designer probiotics 遥控设计益生菌

IF 19.4 1区生物学

Nature Microbiology Pub Date : 2025-07-28 DOI: 10.1038/s41564-025-02072-x

David Carreño, David T. Riglar

引用次数: 0

Ingestible optoelectronic capsules enable bidirectional communication with engineered microbes for controllable therapeutic interventions 可摄取的光电胶囊能够与工程微生物进行双向通信，以实现可控的治疗干预

IF 19.4 1区生物学

Nature Microbiology Pub Date : 2025-07-28 DOI: 10.1038/s41564-025-02057-w

Xinyu Zhang, Zhijie Feng, Hongxiang Li, Haoyan Yang, Lianyue Li, Chao Zhang, Pengxiu Dai, Hanxin Wang, Huimin Xue, Yaxin Wang, Dawei Sun, Xinyu Liu, Mingshan Li, Shenjunjie Lu, Jing Liu, Taofeng Du, Duo Liu, Hanjie Wang

{"title":"Ingestible optoelectronic capsules enable bidirectional communication with engineered microbes for controllable therapeutic interventions","authors":"Xinyu Zhang, Zhijie Feng, Hongxiang Li, Haoyan Yang, Lianyue Li, Chao Zhang, Pengxiu Dai, Hanxin Wang, Huimin Xue, Yaxin Wang, Dawei Sun, Xinyu Liu, Mingshan Li, Shenjunjie Lu, Jing Liu, Taofeng Du, Duo Liu, Hanjie Wang","doi":"10.1038/s41564-025-02057-w","DOIUrl":"10.1038/s41564-025-02057-w","url":null,"abstract":"Engineered microbes can be used for biomolecular sensing and therapeutic interventions. However, they cannot be monitored and controlled while in vivo. Here we combine optogenetically engineered Escherichia coli Nissle 1917, an ingestible optoelectronic capsule and a wireless smartphone to establish a bidirectional biological–optical–electronic signal processing chain for diagnostic or therapeutic capabilities under user control. As a proof of concept, we engineered E. coli Nissle 1917 to detect inflammation-associated nitric oxide in the pig gut and generate a bioluminescent signal for diagnosis of colitis. This signal is transduced by the optoelectronic capsule into a wireless electrical signal and remotely monitored by a smartphone. Smartphone wireless signals activate LED irradiation in the optoelectronic capsule, in turn activating the microbial expression and secretion of an anti-inflammatory nanobody to alleviate colitis in pigs. This approach highlights the potential for integrating synthetic biology and optoelectronics for digital health monitoring and controllable intervention. A smartphone-controlled ingestible capsule can have a two-way communication with engineered microbes inside the gut via light-induced signals.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"1841-1853"},"PeriodicalIF":19.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719704","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

Within-host bacterial evolution and the emergence of pathogenicity 宿主内细菌进化和致病性的出现

IF 19.4 1区生物学

Nature Microbiology Pub Date : 2025-07-25 DOI: 10.1038/s41564-025-02036-1

Gerry Tonkin-Hill, Christopher Ruis, Stephen D. Bentley, Katrina A. Lythgoe, Josephine M. Bryant

{"title":"Within-host bacterial evolution and the emergence of pathogenicity","authors":"Gerry Tonkin-Hill, Christopher Ruis, Stephen D. Bentley, Katrina A. Lythgoe, Josephine M. Bryant","doi":"10.1038/s41564-025-02036-1","DOIUrl":"10.1038/s41564-025-02036-1","url":null,"abstract":"The use of whole-genome sequencing to monitor bacterial pathogens has provided crucial insights into their within-host evolution, revealing mutagenic and selective processes driving the emergence of antibiotic resistance, immune evasion phenotypes and adaptations that enable sustained human-to-human transmission. Deep genomic and metagenomic sequencing of intra-host pathogen populations is also enhancing our ability to track bacterial transmission, a key component of infection control. This Review discusses the major processes driving bacterial evolution within humans, including both pathogenic and commensal species. Initially, mutational processes, including how mutational signatures reveal pathogen biology, and the selective pressures driving evolution are considered. The dynamics of horizontal gene transfer and intra-host pathogen competition are also examined, followed by a focus on the emergence of bacterial pathogenesis. Finally, the Review focuses on the importance of within-host genetic diversity in tracking bacterial transmission and its implications for infectious disease control and public health. In this Review, Tonkin-Hill et al. discuss the processes driving bacterial evolution and emergence of pathogenesis within hosts, the importance of understanding within-host genetic diversity, and the implications for transmission analysis and infectious disease control.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"1829-1840"},"PeriodicalIF":19.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701419","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

Desmocollin 2 is a dominant entry receptor for Epstein–Barr virus infection of epithelial cells Desmocollin 2是Epstein-Barr病毒感染上皮细胞的主要进入受体

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-07-25 DOI: 10.1038/s41564-025-02067-8

Hua Zhang, Yu-Chun Li, De Pang, Chu Xie, Ting Zhang, Ying Li, Yan Li, Zi-Ying Jiang, Guo-Long Bu, Meng-Meng Liu, Ying-Rou Chen, Han-Xiao Fei, Ruo-Bin Lin, Pei-Huang Wu, Wen-Ting Du, Ge-Xin Zhao, Yi-Ling Luo, Ping Han, Qian Zhong, Cong Sun, Mu-Sheng Zeng

{"title":"Desmocollin 2 is a dominant entry receptor for Epstein–Barr virus infection of epithelial cells","authors":"Hua Zhang, Yu-Chun Li, De Pang, Chu Xie, Ting Zhang, Ying Li, Yan Li, Zi-Ying Jiang, Guo-Long Bu, Meng-Meng Liu, Ying-Rou Chen, Han-Xiao Fei, Ruo-Bin Lin, Pei-Huang Wu, Wen-Ting Du, Ge-Xin Zhao, Yi-Ling Luo, Ping Han, Qian Zhong, Cong Sun, Mu-Sheng Zeng","doi":"10.1038/s41564-025-02067-8","DOIUrl":"https://doi.org/10.1038/s41564-025-02067-8","url":null,"abstract":"<p>Epstein–Barr virus (EBV) can infect B cells and epithelial cells, and cause lymphomas and various epithelial malignancies. During epithelial cell infection, EBV employs a complex combination of viral glycoproteins and host receptors. However, the exact mechanism and whether a dominant receptor exists remain unclear. Here we identify desmocollin 2 (DSC2) as a dominant EBV entry receptor for epithelial cell infection using CRISPR–Cas9 screening. Knockout of <i>DSC2</i> reduced EBV infection in both nasopharyngeal and gastric epithelial cell lines, and infection was rescued when DSC2 expression was restored. Expression of human DSC2 in non-EBV-susceptible hamster cell lines enabled susceptibility to EBV. Furthermore, we found that DSC2 directly binds to EBV glycoprotein H/glycoprotein L through its extracellular domain, particularly the preEC–EC2 regions, which could be targeted by polyclonal antibodies, therefore blocking EBV infection in primary epithelial cells. DSC2 enabled virus entry independent of Ephrin receptor A2. These findings could aid development of currently unavailable animal models and support development of targeted therapies.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"726 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701415","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

Expression level of anti-phage defence systems controls a trade-off between protection range and autoimmunity 抗噬菌体防御系统的表达水平控制着保护范围和自身免疫之间的权衡

IF 19.4 1区生物学

Nature Microbiology Pub Date : 2025-07-25 DOI: 10.1038/s41564-025-02063-y

Nitzan Aframian, Shira Omer Bendori, Tal Hen, Polina Guler, Avigdor Eldar

{"title":"Expression level of anti-phage defence systems controls a trade-off between protection range and autoimmunity","authors":"Nitzan Aframian, Shira Omer Bendori, Tal Hen, Polina Guler, Avigdor Eldar","doi":"10.1038/s41564-025-02063-y","DOIUrl":"10.1038/s41564-025-02063-y","url":null,"abstract":"The evolutionary arms race between bacteria and phages has given rise to elaborate anti-phage defence mechanisms. Although many of these systems have been characterized at the molecular level, the general principles and constraints at play are underexplored. It is broadly recognized that in addition to the protection they provide, these systems also bear a substantial cost. Here we identify an expression-dependent trade-off between the protection range of defence systems and the fitness burden they impose. We first focus on the SpbK system of Bacillus subtilis and then generalize to other systems across a range of bacteria. We show that increasing expression of defence systems enhances their protection range, and provide evidence that this is achieved by overwhelming phage strategies for circumventing bacterial defence. However, for most systems tested, increased expression also leads to self-inflicted toxicity. This trade-off between protection and autoimmunity may shape the evolution of regulatory strategies and favour the coexistence of multiple systems within a single genome. The authors examine several defense systems and find that increased expression enhances their protection range, albeit at a cost of autoimmunity.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"1954-1962"},"PeriodicalIF":19.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701416","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

Single-cell image-based screens identify host regulators of Ebola virus infection dynamics 基于单细胞图像的屏幕识别埃博拉病毒感染动态的宿主调节因子

IF 19.4 1区生物学

Nature Microbiology Pub Date : 2025-07-24 DOI: 10.1038/s41564-025-02034-3

Rebecca J. Carlson, J. J. Patten, George Stefanakis, Brian Y. Soong, Adityanarayanan Radhakrishnan, Avtar Singh, Naveen Thakur, Kathleen C. F. Sheehan, Gaya K. Amarasinghe, Nir Hacohen, Christopher F. Basler, Daisy W. Leung, Caroline Uhler, Robert A. Davey, Paul C. Blainey

{"title":"Single-cell image-based screens identify host regulators of Ebola virus infection dynamics","authors":"Rebecca J. Carlson, J. J. Patten, George Stefanakis, Brian Y. Soong, Adityanarayanan Radhakrishnan, Avtar Singh, Naveen Thakur, Kathleen C. F. Sheehan, Gaya K. Amarasinghe, Nir Hacohen, Christopher F. Basler, Daisy W. Leung, Caroline Uhler, Robert A. Davey, Paul C. Blainey","doi":"10.1038/s41564-025-02034-3","DOIUrl":"10.1038/s41564-025-02034-3","url":null,"abstract":"Filoviruses such as Ebola virus (EBOV) give rise to frequent epidemics with high case fatality rates while therapeutic options remain limited. Earlier genetic screens aimed to identify potential drug targets for EBOV relied on systems that may not fully recapitulate the virus life cycle. Here we applied an image-based genome-wide CRISPR screen to identify 998 host regulators of EBOV infection in 39,085,093 cells. A deep learning model associated each host factor with a distinct viral replication step. From this we confirmed UQCRB as a post-entry regulator of EBOV RNA replication and show that small-molecule UQCRB inhibition reduced virus infection in vitro. Using a random forest model, we found that perturbations on STRAP (a spliceosome-associated factor) disrupted the equilibrium between viral RNA and protein. STRAP was associated with VP35, a viral RNA processing protein. This genome-wide screen coupled with 12 secondary screens including validation experiments with Sudan and Marburg virus, presents a rich resource for host regulators of virus replication and potential targets for therapeutic intervention. A single-cell resolution image-based genome-wide CRISPR screen, analysed with deep learning and random forest models, identified host factors regulating Ebola virus infection at distinct stages in the viral life cycle.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"1989-2002"},"PeriodicalIF":19.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694062","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

Genome-resolved long-read sequencing expands known microbial diversity across terrestrial habitats 基因组解析的长读测序扩展了已知的陆地栖息地微生物多样性

IF 19.4 1区生物学

Nature Microbiology Pub Date : 2025-07-24 DOI: 10.1038/s41564-025-02062-z

Mantas Sereika, Aaron James Mussig, Chenjing Jiang, Kalinka Sand Knudsen, Thomas Bygh Nymann Jensen, Francesca Petriglieri, Yu Yang, Vibeke Rudkjøbing Jørgensen, Francesco Delogu, Emil Aarre Sørensen, Per Halkjær Nielsen, Caitlin Margaret Singleton, Philip Hugenholtz, Mads Albertsen

{"title":"Genome-resolved long-read sequencing expands known microbial diversity across terrestrial habitats","authors":"Mantas Sereika, Aaron James Mussig, Chenjing Jiang, Kalinka Sand Knudsen, Thomas Bygh Nymann Jensen, Francesca Petriglieri, Yu Yang, Vibeke Rudkjøbing Jørgensen, Francesco Delogu, Emil Aarre Sørensen, Per Halkjær Nielsen, Caitlin Margaret Singleton, Philip Hugenholtz, Mads Albertsen","doi":"10.1038/s41564-025-02062-z","DOIUrl":"10.1038/s41564-025-02062-z","url":null,"abstract":"The emergence of high-throughput, long-read DNA sequencing has enabled recovery of microbial genomes from environmental samples at scale. However, expanding the terrestrial microbial genome catalogue has been challenging due to the enormous complexity of these environments. Here we performed deep, long-read Nanopore sequencing of 154 soil and sediment samples collected during the Microflora Danica project, yielding genomes of 15,314 previously undescribed microbial species, recovered using our custom mmlong2 workflow. The recovered microbial genomes span 1,086 previously uncharacterized genera and expand the phylogenetic diversity of the prokaryotic tree of life by 8%. The long-read assemblies also enabled the recovery of thousands of complete ribosomal RNA operons, biosynthetic gene clusters and CRISPR-Cas systems. Furthermore, the incorporation of the recovered genomes into public genomic databases substantially improved species-level classification rates for soil and sediment metagenomic datasets. These findings demonstrate that long-read sequencing allows cost-effective recovery of high-quality microbial genomes from highly complex ecosystems, which remain an untapped source of biodiversity. Nanopore sequencing of Danish soils and sediments yields genomes from over 15,000 microbial species, expanding the phylogenetic diversity of prokaryotes by 8%.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"2018-2030"},"PeriodicalIF":19.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02062-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694063","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