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Cas10 relieves host growth arrest to facilitate spacer retention during type III-A CRISPR-Cas immunity
IF 30.3 1区 医学
Cell host & microbe Pub Date : 2024-12-02 DOI: 10.1016/j.chom.2024.11.005
Naama Aviram, Amanda K. Shilton, Nia G. Lyn, Bernardo S. Reis, Amir Brivanlou, Luciano A. Marraffini
{"title":"Cas10 relieves host growth arrest to facilitate spacer retention during type III-A CRISPR-Cas immunity","authors":"Naama Aviram, Amanda K. Shilton, Nia G. Lyn, Bernardo S. Reis, Amir Brivanlou, Luciano A. Marraffini","doi":"10.1016/j.chom.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.chom.2024.11.005","url":null,"abstract":"Cells from all kingdoms of life can enter growth arrest in unfavorable environmental conditions. Key to this process are mechanisms enabling recovery from this state. Staphylococcal type III-A CRISPR-Cas loci encode the Cas10 complex that uses a guide RNA to locate complementary viral transcripts and start an immune response. When the target sequence is expressed late in the viral lytic cycle, defense requires the activity of Csm6, a non-specific RNase that inhibits the growth of the infected cell. How Csm6 protects from infection and whether growth can be restored is not known. Here, we show that growth arrest provides immunity at the population level, preventing viral replication and allowing uninfected cells to propagate. In addition, the ssDNase activity of Cas10 is required for the regrowth of a subset of the arrested cells and the recovery of the infected host, presumably ending the immune response through degradation of the viral DNA.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"12 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Campylobacter jejuni-derived cytolethal distending toxin promotes colorectal cancer metastasis
IF 30.3 1区 医学
Cell host & microbe Pub Date : 2024-12-02 DOI: 10.1016/j.chom.2024.11.006
Zhen He, Jing Yu, Junli Gong, Jinjie Wu, Xuan Zong, Zhanhao Luo, Xiaowen He, Wai Ming Cheng, Yugeng Liu, Chen Liu, Qiang Zhang, Lei Dai, Tao Ding, Beile Gao, Raad Z. Gharaibeh, Jinlin Huang, Christian Jobin, Ping Lan
{"title":"Campylobacter jejuni-derived cytolethal distending toxin promotes colorectal cancer metastasis","authors":"Zhen He, Jing Yu, Junli Gong, Jinjie Wu, Xuan Zong, Zhanhao Luo, Xiaowen He, Wai Ming Cheng, Yugeng Liu, Chen Liu, Qiang Zhang, Lei Dai, Tao Ding, Beile Gao, Raad Z. Gharaibeh, Jinlin Huang, Christian Jobin, Ping Lan","doi":"10.1016/j.chom.2024.11.006","DOIUrl":"https://doi.org/10.1016/j.chom.2024.11.006","url":null,"abstract":"Various forms of solid tumors harbor intracellular bacteria, but the physiological consequences of these microorganisms are poorly understood. We show that <em>Campylobacter</em> is significantly enriched in primary colorectal cancer (CRC) lesions from patients with metastasis. <em>Campylobacter</em> <em>jejuni</em>-derived cytolethal distending toxin (CDT) promotes CRC metastasis through JAK2-STAT3-MMP9 signaling in liver or pulmonary metastatic mice models, as confirmed in <em>C. jejuni</em>-infected human colonic tissue and CDT-treated colonic tumoroids from patients. Genetic deletion of <em>cdtB</em> (<em>ΔcdtB</em>) or purified CdtB protein demonstrates that the genotoxin is essential for <em>C. jejuni’s</em> pro-metastatic property. In <em>C.-jejuni</em>-colonized mice, increased translocation of CDT-producing <em>C. jejuni</em> to extraintestinal implanted tumors potentially leads to accelerated metastasis of these tumors. Overall, these findings demonstrate that an intratumor-bacteria-derived genotoxin accelerates tumor metastasis, potentially opening a new diagnostic and therapeutic avenue for cancer management.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"17 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19
IF 30.3 1区 医学
Cell host & microbe Pub Date : 2024-11-29 DOI: 10.1016/j.chom.2024.11.007
Zhouyi Rong, Hongcheng Mai, Gregor Ebert, Saketh Kapoor, Victor G. Puelles, Jan Czogalla, Senbin Hu, Jinpeng Su, Danilo Prtvar, Inderjeet Singh, Julia Schädler, Claire Delbridge, Hanno Steinke, Hannah Frenzel, Katja Schmidt, Christian Braun, Gina Bruch, Viktoria Ruf, Mayar Ali, Kurt-Wolfram Sühs, Ali Ertürk
{"title":"Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19","authors":"Zhouyi Rong, Hongcheng Mai, Gregor Ebert, Saketh Kapoor, Victor G. Puelles, Jan Czogalla, Senbin Hu, Jinpeng Su, Danilo Prtvar, Inderjeet Singh, Julia Schädler, Claire Delbridge, Hanno Steinke, Hannah Frenzel, Katja Schmidt, Christian Braun, Gina Bruch, Viktoria Ruf, Mayar Ali, Kurt-Wolfram Sühs, Ali Ertürk","doi":"10.1016/j.chom.2024.11.007","DOIUrl":"https://doi.org/10.1016/j.chom.2024.11.007","url":null,"abstract":"SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes. Similar distribution patterns of the spike protein were observed in SARS-CoV-2-infected mice. Injection of spike protein alone was sufficient to induce neuroinflammation, proteome changes in the skull-meninges-brain axis, anxiety-like behavior, and exacerbated outcomes in mouse models of stroke and traumatic brain injury. Vaccination reduced but did not eliminate spike protein accumulation after infection in mice. Our findings suggest persistent spike protein at the brain borders may contribute to lasting neurological sequelae of COVID-19.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"17 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protection against Clostridioides difficile disease by a naturally avirulent strain 用天然无毒菌株预防艰难梭菌病
IF 30.3 1区 医学
Cell host & microbe Pub Date : 2024-11-27 DOI: 10.1016/j.chom.2024.11.003
Qiwen Dong, Stephen Harper, Emma McSpadden, Sophie S. Son, Marie-Maude Allen, Huaiying Lin, Rita C. Smith, Carolyn Metcalfe, Victoria Burgo, Che Woodson, Anitha Sundararajan, Amber Rose, Mary McMillin, David Moran, Jessica Little, Michael W. Mullowney, Ashley M. Sidebottom, Louis-Charles Fortier, Aimee Shen, Eric G. Pamer
{"title":"Protection against Clostridioides difficile disease by a naturally avirulent strain","authors":"Qiwen Dong, Stephen Harper, Emma McSpadden, Sophie S. Son, Marie-Maude Allen, Huaiying Lin, Rita C. Smith, Carolyn Metcalfe, Victoria Burgo, Che Woodson, Anitha Sundararajan, Amber Rose, Mary McMillin, David Moran, Jessica Little, Michael W. Mullowney, Ashley M. Sidebottom, Louis-Charles Fortier, Aimee Shen, Eric G. Pamer","doi":"10.1016/j.chom.2024.11.003","DOIUrl":"https://doi.org/10.1016/j.chom.2024.11.003","url":null,"abstract":"<em>Clostridioides difficile</em> is a leading cause of healthcare infections. Gut dysbiosis promotes <em>C. difficile</em> infection (CDI) and CDIs promote gut dysbiosis, leading to frequent CDI recurrence. Although therapies preventing recurrent CDI have been developed, including live biotherapeutic products, existing therapies are costly and do not prevent primary infections. Here, we show that an avirulent <em>C. difficile</em> isolate, ST1-75, protects mice from developing colitis induced by a virulent R20291 strain when coinfected at a 1:1 ratio. In metabolic analyses, avirulent ST1-75 depletes amino acids more rapidly than virulent R20291 and supplementation with amino acids ablates this competitive advantage, indicating that ST1-75 limits the growth of virulent R20291 through amino acid depletion. Overall, our study identifies inter-strain nutrient depletion as a potentially exploitable mechanism to reduce the incidence of CDI and reveals that the ST1-75 strain may be a biotherapeutic agent that can prevent CDI in high-risk patients.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"1 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Zinc promotes microbial p-coumaric acid production that protects against cholestatic liver injury 锌能促进微生物产生对香豆酸,从而防止胆汁淤积性肝损伤
IF 30.3 1区 医学
Cell host & microbe Pub Date : 2024-11-27 DOI: 10.1016/j.chom.2024.11.002
Dongping Li, Meijuan Wan, Lanfeng Xue, Zhelin Zhang, Yifeng Qiu, Fengyi Mei, Niexing Tang, Chunxiao Yu, Yao Yu, Tianqi Chen, Xing Ding, Qin Yang, Qiuyan Liu, Peng Gu, Wei Jia, Yu Chen, Peng Chen
{"title":"Zinc promotes microbial p-coumaric acid production that protects against cholestatic liver injury","authors":"Dongping Li, Meijuan Wan, Lanfeng Xue, Zhelin Zhang, Yifeng Qiu, Fengyi Mei, Niexing Tang, Chunxiao Yu, Yao Yu, Tianqi Chen, Xing Ding, Qin Yang, Qiuyan Liu, Peng Gu, Wei Jia, Yu Chen, Peng Chen","doi":"10.1016/j.chom.2024.11.002","DOIUrl":"https://doi.org/10.1016/j.chom.2024.11.002","url":null,"abstract":"Cholestatic liver disease (CLD) is a common liver disorder with limited treatment options. Here, we demonstrate that zinc (Zn) supplementation can alter the gut microbiome to mitigate cholestatic liver injury. Oral Zn altered the microbiota of mice and humans (this study was registered at <span><span>clinicaltrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> [NCT05597137]), increasing the abundance of <em>Blautia producta</em> (<em>B. producta</em>) and promoting the generation of p-coumaric acid. Additionally, p-coumaric acid concentrations were negatively correlated with liver injury parameters in CLD patients. In mice, the protective effects of Zn were partially mediated by p-coumaric acid, which directly bound to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and suppressed the production of reactive oxygen species (ROS) in hepatocytes, thus preventing hepatocyte cell death and liver damage. Additionally, knocking out the histidine ammonia-lyase, which catalyzes the conversion of tyrosine to p-coumaric acid in <em>B. producta</em>, blunted the protective effects of Zn. These findings highlight a host-microbiota interaction that is stimulated by Zn supplementation, providing potential benefits for CLD.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"79 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A nucleoside signal generated by a fungal endophyte regulates host cell death and promotes root colonization 真菌内生菌产生的核苷信号可调控宿主细胞死亡并促进根系定殖
IF 30.3 1区 医学
Cell host & microbe Pub Date : 2024-11-26 DOI: 10.1016/j.chom.2024.10.020
Nick Dunken, Heidi Widmer, Gerd U. Balcke, Henryk Straube, Gregor Langen, Nyasha M. Charura, Pia Saake, Concetta De Quattro, Jonas Schön, Hanna Rövenich, Stephan Wawra, Mamoona Khan, Armin Djamei, Matias D. Zurbriggen, Alain Tissier, Claus-Peter Witte, Alga Zuccaro
{"title":"A nucleoside signal generated by a fungal endophyte regulates host cell death and promotes root colonization","authors":"Nick Dunken, Heidi Widmer, Gerd U. Balcke, Henryk Straube, Gregor Langen, Nyasha M. Charura, Pia Saake, Concetta De Quattro, Jonas Schön, Hanna Rövenich, Stephan Wawra, Mamoona Khan, Armin Djamei, Matias D. Zurbriggen, Alain Tissier, Claus-Peter Witte, Alga Zuccaro","doi":"10.1016/j.chom.2024.10.020","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.020","url":null,"abstract":"The intracellular colonization of plant roots by the beneficial fungal endophyte <em>Serendipita indica</em> follows a biphasic strategy, including a host cell death phase that enables successful colonization of <em>Arabidopsis thaliana</em> roots. How host cell death is initiated and controlled is largely unknown. Here, we show that two fungal enzymes, the ecto-5′-nucleotidase <em>Si</em>E5NT and the nuclease <em>Si</em>NucA, act synergistically in the apoplast at the onset of cell death to produce deoxyadenosine (dAdo). The uptake of extracellular dAdo but not the structurally related adenosine activates cell death via the equilibrative nucleoside transporter ENT3. We identified a previously uncharacterized Toll-like interleukin 1 receptor (TIR)-nucleotide-binding leucine-rich repeat receptor (NLR) protein, ISI (induced by <em>S. indica</em>), as an intracellular factor that affects host cell death, fungal colonization, and growth promotion. Our data show that the combined activity of two fungal apoplastic enzymes promotes the production of a metabolite that engages TIR-NLR-modulated pathways to induce plant cell death, providing a link to immunometabolism in plants.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"64 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prenatal antibiotics reduce breast milk IgA and induce dysbiosis in mouse offspring, increasing neonatal susceptibility to bacterial sepsis 产前抗生素会降低母乳中的 IgA,诱发小鼠后代菌群失调,增加新生儿对细菌性败血症的易感性
IF 30.3 1区 医学
Cell host & microbe Pub Date : 2024-11-26 DOI: 10.1016/j.chom.2024.11.001
Carlo Pietrasanta, Carolina Carlosama, Michela Lizier, Giulia Fornasa, Tanja Rezzonico Jost, Sara Carloni, Silvia Giugliano, Alessandra Silvestri, Paola Brescia, Benedetta De Ponte Conti, Daniele Braga, Martin Mihula, Lavinia Morosi, Alessandro Bernardinello, Andrea Ronchi, Giuseppe Martano, Fabio Mosca, Giuseppe Penna, Fabio Grassi, Lorenza Pugni, Maria Rescigno
{"title":"Prenatal antibiotics reduce breast milk IgA and induce dysbiosis in mouse offspring, increasing neonatal susceptibility to bacterial sepsis","authors":"Carlo Pietrasanta, Carolina Carlosama, Michela Lizier, Giulia Fornasa, Tanja Rezzonico Jost, Sara Carloni, Silvia Giugliano, Alessandra Silvestri, Paola Brescia, Benedetta De Ponte Conti, Daniele Braga, Martin Mihula, Lavinia Morosi, Alessandro Bernardinello, Andrea Ronchi, Giuseppe Martano, Fabio Mosca, Giuseppe Penna, Fabio Grassi, Lorenza Pugni, Maria Rescigno","doi":"10.1016/j.chom.2024.11.001","DOIUrl":"https://doi.org/10.1016/j.chom.2024.11.001","url":null,"abstract":"Antibiotics (Abx) are administered to 20%–30% of pregnant women, but their effects on neonatal immune development are poorly understood. We show that newborn mice born to Abx-treated dams are more susceptible to late-onset sepsis. This susceptibility is linked to lower maternal breast milk immunoglobulin A (IgA), neonatal fecal IgA, and IgA coating of intestinal bacteria, thus causing the translocation of intestinal pathobionts. Weaned young adults born to Abx-treated mothers had reduced IgA+ plasma cells in the ileum and colon, fecal secretory IgA (SIgA), colonic CD4<sup>+</sup> T regulatory lymphocytes and T helper 17-like lymphocytes, and a less diverse fecal microbiome. However, treatment with apyrase, which restores SIgA secretion, prompted IgA production in breast milk and protected pups from sepsis. Additionally, breast milk from untreated mothers rescued the phenotypes of pups born to Abx-treated mothers. Our data highlight the impact of prenatal Abx on breast milk IgA and their long-term influence on intestinal mucosal immune function mediated by breastfeeding.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"4688 1 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A metagenome-assembled genome inventory for children reveals early-life gut bacteriome and virome dynamics 元基因组组装的儿童基因组清单揭示了生命早期肠道细菌组和病毒组的动态变化
IF 30.3 1区 医学
Cell host & microbe Pub Date : 2024-11-25 DOI: 10.1016/j.chom.2024.10.017
Ye Peng, Jie Zhu, Shilan Wang, Yingzhi Liu, Xin Liu, Orlando DeLeon, Wenyi Zhu, Zhilu Xu, Xi Zhang, Shilin Zhao, Suisha Liang, Hang Li, Brian Ho, Jessica Yuet-Ling Ching, Chun Pan Cheung, Ting Fan Leung, Wing Hung Tam, Tak Yeung Leung, Eugene B. Chang, Francis Ka Leung Chan, Hein Min Tun
{"title":"A metagenome-assembled genome inventory for children reveals early-life gut bacteriome and virome dynamics","authors":"Ye Peng, Jie Zhu, Shilan Wang, Yingzhi Liu, Xin Liu, Orlando DeLeon, Wenyi Zhu, Zhilu Xu, Xi Zhang, Shilin Zhao, Suisha Liang, Hang Li, Brian Ho, Jessica Yuet-Ling Ching, Chun Pan Cheung, Ting Fan Leung, Wing Hung Tam, Tak Yeung Leung, Eugene B. Chang, Francis Ka Leung Chan, Hein Min Tun","doi":"10.1016/j.chom.2024.10.017","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.017","url":null,"abstract":"Existing microbiota databases are biased toward adult samples, hampering accurate profiling of the infant gut microbiome. Here, we generated a metagenome-assembled genome inventory for children (MAGIC) from a large collection of bulk and viral-like particle-enriched metagenomes from 0 to 7 years of age, encompassing 3,299 prokaryotic and 139,624 viral species-level genomes, 8.5% and 63.9% of which are unique to MAGIC. MAGIC improves early-life microbiome profiling, with the greatest improvement in read mapping observed in Africans. We then identified 54 candidate keystone species, including several <em>Bifidobacterium</em> spp. and four phages, forming guilds that fluctuated in abundance with time. Their abundances were reduced in preterm infants and were associated with childhood allergies. By analyzing the <em>B. longum</em> pangenome, we found evidence of phage-mediated evolution and quorum sensing-related ecological adaptation. Together, the MAGIC database recovers genomes that enable characterization of the dynamics of early-life microbiomes, identification of candidate keystone species, and strain-level study of target species.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"1 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A trivalent mucosal vaccine encoding phylogenetically inferred ancestral RBD sequences confers pan-Sarbecovirus protection in mice 编码系统发育推断出的祖先 RBD 序列的三价粘膜疫苗可为小鼠提供泛沙巴病毒保护
IF 30.3 1区 医学
Cell host & microbe Pub Date : 2024-11-18 DOI: 10.1016/j.chom.2024.10.016
James Brett Case, Shilpa Sanapala, Carly Dillen, Victoria Rhodes, Christian Zmasek, Taras M. Chicz, Charlotte E. Switzer, Suzanne M. Scheaffer, George Georgiev, Catherine Jacob-Dolan, Blake M. Hauser, Déborah Carolina Carvalho Dos Anjos, Lucas J. Adams, Nadia Soudani, Chieh-Yu Liang, Baoling Ying, Ryan P. McNamara, Richard H. Scheuermann, Adrianus C.M. Boon, Daved H. Fremont, Michael S. Diamond
{"title":"A trivalent mucosal vaccine encoding phylogenetically inferred ancestral RBD sequences confers pan-Sarbecovirus protection in mice","authors":"James Brett Case, Shilpa Sanapala, Carly Dillen, Victoria Rhodes, Christian Zmasek, Taras M. Chicz, Charlotte E. Switzer, Suzanne M. Scheaffer, George Georgiev, Catherine Jacob-Dolan, Blake M. Hauser, Déborah Carolina Carvalho Dos Anjos, Lucas J. Adams, Nadia Soudani, Chieh-Yu Liang, Baoling Ying, Ryan P. McNamara, Richard H. Scheuermann, Adrianus C.M. Boon, Daved H. Fremont, Michael S. Diamond","doi":"10.1016/j.chom.2024.10.016","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.016","url":null,"abstract":"The continued emergence of SARS-CoV-2 variants and the threat of future Sarbecovirus zoonoses have spurred the design of vaccines that can induce broad immunity against multiple coronaviruses. Here, we use computational methods to infer ancestral phylogenetic reconstructions of receptor binding domain (RBD) sequences across multiple Sarbecovirus clades and incorporate them into a multivalent adenoviral-vectored vaccine. Mice immunized with this pan-Sarbecovirus vaccine are protected in the upper and lower respiratory tracts against infection by historical and contemporary SARS-CoV-2 variants, SARS-CoV, and pre-emergent SHC014 and Pangolin/GD coronavirus strains. Using genetic and immunological approaches, we demonstrate that vaccine-induced protection unexpectedly is conferred principally by CD4<sup>+</sup> and CD8<sup>+</sup> T cell-mediated anamnestic responses. Importantly, prior mRNA vaccination or SARS-CoV-2 respiratory infection does not alter the efficacy of the mucosally delivered pan-Sarbecovirus vaccine. These data highlight the promise of a phylogenetic approach for antigen and vaccine design against existing and pre-emergent Sarbecoviruses with pandemic potential.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"8 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Harnessing biosynthesized selenium nanoparticles for recruitment of beneficial soil microbes to plant roots 利用生物合成的硒纳米颗粒招募有益的土壤微生物进入植物根系
IF 30.3 1区 医学
Cell host & microbe Pub Date : 2024-11-18 DOI: 10.1016/j.chom.2024.10.015
Chenyu Sun, Bin Sun, Lin Chen, Meilin Zhang, Pingping Lu, Mengfan Wu, Quanhong Xue, Qiao Guo, Dejian Tang, Hangxian Lai
{"title":"Harnessing biosynthesized selenium nanoparticles for recruitment of beneficial soil microbes to plant roots","authors":"Chenyu Sun, Bin Sun, Lin Chen, Meilin Zhang, Pingping Lu, Mengfan Wu, Quanhong Xue, Qiao Guo, Dejian Tang, Hangxian Lai","doi":"10.1016/j.chom.2024.10.015","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.015","url":null,"abstract":"Root exudates can benefit plant growth and health by reshaping the rhizosphere microbiome. Whether nanoparticles biosynthesized by rhizosphere microbes play a similar role in plant microbiome manipulation remains enigmatic. Herein, we collect elemental selenium nanoparticles (SeNPs) from selenobacteria associated with maize roots. <em>In vitro</em> and soil assays show that the SeNPs enhanced plant performance by recruiting plant growth-promoting bacteria (e.g., <em>Bacillus</em>) in a dose-dependent manner. Multiomic profilings unravel a cross-kingdom-signaling cascade that mediates efficient biosynthesis of SeNPs by selenobacteria. Specifically, maize roots perceive histamine signaling from <em>Bacillus</em> spp., which stimulates the plant to produce <em>p</em>-coumarate via root exudation. The <em>rpoS</em> gene in selenobacteria (e.g., <em>Pseudomonas</em> sp. ZY71) responds to <em>p</em>-coumarate signaling and positively regulates the biosynthesis of SeNPs. This study demonstrates a novel mechanism for recruiting host-beneficial soil microbes by microbially synthesized nanoparticles and unlocks promising possibilities for plant microbiome manipulation.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"21 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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