Yuanyuan Liu, Zhiwei Zhou, J. Bryce Jarman, Haoqing Chen, Michelle Miranda-Velez, Robert Terkeltaub, Dylan Dodd
{"title":"Gut bacteria degrade purines via the 2,8-dioxopurine pathway","authors":"Yuanyuan Liu, Zhiwei Zhou, J. Bryce Jarman, Haoqing Chen, Michelle Miranda-Velez, Robert Terkeltaub, Dylan Dodd","doi":"10.1038/s41564-025-02079-4","DOIUrl":"10.1038/s41564-025-02079-4","url":null,"abstract":"Approximately one-third of urate, which at elevated levels contributes to hyperuricaemia and gout, is excreted into the intestinal tract of healthy individuals where bacteria aid its elimination. However, the molecular details of purine metabolism in the gut microbiome are unclear. Here we uncovered the 2,8-dioxopurine pathway, an anaerobic route for purine degradation in the gut bacteria, Clostridium sporogenes and Escherichia coli. Reconstitution with purified enzymes and mutational analysis combined with isotope tracking and mass spectrometry identified a selenium-dependent enzyme, 2,8-dioxopurine dehydrogenase (DOPDH), and seven additional enzymes that connect purine metabolism to short-chain fatty acid synthesis and ATP generation (measured via luciferase assay). Competition experiments in gnotobiotic mice showed that bacteria harbouring this pathway exhibit a fitness advantage, with wild-type bacteria rapidly outcompeting a DOPDH-deficient strain. Widespread presence of these genes across host-associated microbiomes suggests a host–microbe symbiosis, where host-secreted urate fosters a metabolic niche for bacteria that break it down. These findings could have therapeutic implications for the modification and enhancement of intestinal elimination of urate. Utilizing a selenium-dependent enzyme, gut bacteria degrade uric acid via a previously unrecognized anaerobic pathway which gives them a competitive advantage in the gut.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 9","pages":"2291-2305"},"PeriodicalIF":19.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786651","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}
{"title":"Applying ecological principles to microbiome engineering","authors":"Lucas P. Henry, Joy Bergelson","doi":"10.1038/s41564-025-02076-7","DOIUrl":"10.1038/s41564-025-02076-7","url":null,"abstract":"Microbiome engineering seeks to reshape microbial communities to improve ecosystem function. However, many efforts fail due to inadequate design principles, often resulting in a loss of key microorganisms and disruption of links between the engineered community and its intended function. In contrast, decades of research in macroecology have uncovered key principles governing the relationship between biodiversity and ecosystem function. Here we translate these ecological principles to microbiome engineering, focusing on three stages: microbiome design, colonization and maintenance. We propose new approaches that leverage underlying ecological dynamics—particularly niche dynamics—to optimize diversity and abundance to promote stability and functionality, especially in host-associated microbiomes. We also highlight key research priorities to apply macro-ecosystem insights to microbial systems. Improving microbiome engineering in this way holds promise for solving pressing challenges in medicine and agriculture, while providing understanding of ecological processes that maintain biodiversity across biological scales. This Perspective discusses the application of ecological principles of macro-ecosystems to microbiome engineering. The authors propose research priorities necessary to facilitate the application of these ecological principles to improve microbiome functionality.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 9","pages":"2111-2121"},"PeriodicalIF":19.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778595","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}
{"title":"Metal-induced conformational changes in the Sabiá virus spike complex","authors":"Hadas Cohen-Dvashi, Michael Katz, Ron Diskin","doi":"10.1038/s41564-025-02075-8","DOIUrl":"10.1038/s41564-025-02075-8","url":null,"abstract":"Haemorrhagic fever viruses from the Arenaviridae are a source of concern owing to their potential to cause lethal outbreaks and the lack of effective therapeutics. While structures of spike proteins from ‘Old World’ arenaviruses are available, the differences and similarities to ‘New World’ arenaviruses, such as the Sabiá virus, remain unclear owing to the lack of New World spike structures. Here we present the structure of the isolated spike complex from the Sabiá virus, which mediates viral attachment and entry to the host cells, using single-particle cryo-electron microscopy. We find two distinct conformational states of the spike, representing its native closed state at 2.6 Å resolution and an open state at 2.9 Å resolution that it assumes during cell entry. In addition, we show that the opening of the spike and subsequent cell entry are dependent on acidic pH and an unidentified metal ion. Our study suggests potential differences in the cell entry mechanisms of clade B arenaviruses compared with others in the Arenaviridae family. The Sabiá virus spike complex undergoes conformational changes upon cell entry, from a native closed to an open state, which is dependent on pH and a metal ion.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 9","pages":"2221-2230"},"PeriodicalIF":19.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756632","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}
{"title":"HIV-1 capsid found guilty of breaking and entering","authors":"Adarsh Dharan, Edward M. Campbell","doi":"10.1038/s41564-025-02071-y","DOIUrl":"10.1038/s41564-025-02071-y","url":null,"abstract":"Two new studies find that HIV-1 can enter the nucleus by cracking or distorting nuclear pore structures, explaining how the HIV-1 capsid can seemingly ignore the size limitations associated with conventional nuclear import.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"1800-1801"},"PeriodicalIF":19.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747386","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}
{"title":"Rethinking approaches to overcome infectious disease","authors":"","doi":"10.1038/s41564-025-02093-6","DOIUrl":"10.1038/s41564-025-02093-6","url":null,"abstract":"We summarize our Focus issue on ‘Strategies to overcome infectious disease’ and present some of the approaches to tackle heightening rates of infectious diseases.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"1791-1792"},"PeriodicalIF":19.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02093-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756284","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}
Yong Fan, Liwei Lyu, Ruben Vazquez-Uribe, Wanliang Zhang, Mareike Bongers, Andreas Koulouktsis, Mengliu Yang, Vita Sereika-Bejder, Tulika Arora, Evelina Stankevic, Jeremy Armetta, Franziska Zosel, Charlotta D. de la Cour, Lotte Simonsen, Alina Kulakova, Michael Wierer, Pernille Harris, Joachim Gæde, Peter Rossing, Filip K. Knop, Tune H. Pers, Tue Haldor Hansen, Trine Nielsen, Ling Li, Kristian Strømgaard, Gangyi Yang, Morten Otto Alexander Sommer, Oluf Pedersen
{"title":"Polypeptides synthesized by common bacteria in the human gut improve rodent metabolism","authors":"Yong Fan, Liwei Lyu, Ruben Vazquez-Uribe, Wanliang Zhang, Mareike Bongers, Andreas Koulouktsis, Mengliu Yang, Vita Sereika-Bejder, Tulika Arora, Evelina Stankevic, Jeremy Armetta, Franziska Zosel, Charlotta D. de la Cour, Lotte Simonsen, Alina Kulakova, Michael Wierer, Pernille Harris, Joachim Gæde, Peter Rossing, Filip K. Knop, Tune H. Pers, Tue Haldor Hansen, Trine Nielsen, Ling Li, Kristian Strømgaard, Gangyi Yang, Morten Otto Alexander Sommer, Oluf Pedersen","doi":"10.1038/s41564-025-02064-x","DOIUrl":"10.1038/s41564-025-02064-x","url":null,"abstract":"The human gut microbiota has the potential to synthesize proteins that may influence host metabolism. Here we report two polypeptides, RUMTOR-derived peptide (RORDEP) 1 and RORDEP2, circulating in human blood and synthesized by specific strains of gut commensal Ruminococcus torques that correlate inversely with adiposity in humans. Oral gavage with RORDEP-expressing strains improved glucose tolerance, increased bone density and reduced fat mass with an enhanced expression of genes and proteins involved in thermogenesis and lipolysis in lean mice on a high-fat diet and diet-induced obese mice. Recombinant RORDEP1 given to rats intraperitoneally decreased plasma gastric inhibitory polypeptide but increased glucagon-like peptide 1, peptide YY and insulin. Intestinal delivery of recombinant RORDEP1 to rats potentiated insulin-mediated inhibition of hepatic glucose production by downregulating genes and proteins controlling liver gluconeogenesis, glycogenolysis and lipogenesis but upregulating those involved in insulin signalling, glycogenesis and glycolysis. These preclinical findings warrant the exploration of RORDEPs for the prevention and treatment of human metabolic disorders. Two polypeptides synthesized by common bacterial strains in human gut microbiota lower body fat and blood glucose and increase bone density, improving the metabolism of rodents.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"1918-1939"},"PeriodicalIF":19.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02064-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747387","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}
{"title":"From farm to factory to fork","authors":"Kate S. Baker, Alison E. Mather","doi":"10.1038/s41564-025-02069-6","DOIUrl":"10.1038/s41564-025-02069-6","url":null,"abstract":"A recent study has examined the flow of antimicrobial resistance genes in food production using nearly 2,000 metagenomes, indicating a potential role for contamination in processing facilities.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"1798-1799"},"PeriodicalIF":19.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747385","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}
{"title":"Deep, long-read metagenome sequencing expands knowledge of prokaryotic phylogenetic diversity","authors":"","doi":"10.1038/s41564-025-02073-w","DOIUrl":"10.1038/s41564-025-02073-w","url":null,"abstract":"Deep, long-read metagenome sequencing of 154 soil and sediment samples from diverse habitats in Denmark enabled recovery of 4,894 high-quality and highly contiguous microbial genomes. The vast untapped microbial diversity in complex ecosystems can now be systematically explored, categorized and capitalized on.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"1802-1803"},"PeriodicalIF":19.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747586","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}
Narciso M. Quijada, José F. Cobo-Díaz, Vincenzo Valentino, Coral Barcenilla, Francesca De Filippis, Raul Cabrera-Rubio, Niccolò Carlino, Federica Pinto, Monika Dzieciol, Inés Calvete-Torre, Carlos Sabater, Francesco Rubino, Stephen Knobloch, Sigurlaug Skirnisdottir, Lorena Ruiz, Mercedes López, Miguel Prieto, Viggó Thór Marteinsson, Abelardo Margolles, Nicola Segata, Paul D. Cotter, Martin Wagner, Danilo Ercolini, Avelino Alvarez-Ordóñez
{"title":"The food-associated resistome is shaped by processing and production environments","authors":"Narciso M. Quijada, José F. Cobo-Díaz, Vincenzo Valentino, Coral Barcenilla, Francesca De Filippis, Raul Cabrera-Rubio, Niccolò Carlino, Federica Pinto, Monika Dzieciol, Inés Calvete-Torre, Carlos Sabater, Francesco Rubino, Stephen Knobloch, Sigurlaug Skirnisdottir, Lorena Ruiz, Mercedes López, Miguel Prieto, Viggó Thór Marteinsson, Abelardo Margolles, Nicola Segata, Paul D. Cotter, Martin Wagner, Danilo Ercolini, Avelino Alvarez-Ordóñez","doi":"10.1038/s41564-025-02059-8","DOIUrl":"10.1038/s41564-025-02059-8","url":null,"abstract":"Food production systems may act as transmission routes for antimicrobial-resistant (AMR) bacteria and AMR genes (AMRGs) to humans. However, the food resistome remains poorly characterized. Here 1,780 raw-material (milk, brine, fresh meat and so on), end-product (cheese, fish, meat products and vegetables) and surface (processing, cooling, smoking, ripening and packing rooms) samples from 113 food processing facilities were subjected to whole-metagenome sequencing. Assembly-free analyses demonstrated that >70% of all known AMRGs, including many predicted to confer resistance to critically important antibiotics, circulate throughout food production chains, with those conferring resistance to tetracyclines, β-lactams, aminoglycosides and macrolides being the most abundant overall. An assembly-based analysis highlighted that bacteria from the ESKAPEE group, together with Staphylococcus equorum and Acinetobacter johnsonii, were the main AMRG carriers. Further evaluation demonstrated that ~40% of the AMRGs were associated with mobile genetic elements, mainly plasmids. These findings will help guide the appropriate use of biocides and other antimicrobials in food production settings when designing efficient antimicrobial stewardship policies. Whole-metagenome sequencing of 1,780 raw-material, end-product and surface samples from 113 food processing facilities reveals the occurrence of antimicrobial resistance determinants in foods and their processing environments.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"1854-1867"},"PeriodicalIF":19.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02059-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737012","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}
Virginie Girault, Alexey Stukalov, Madalina Elena Carter-Timofte, Jonny Hertzog, Melissa Verin, Katharina Austen, Darya A. Haas, Lila Oubraham, Antonio Piras, Susanne Maidl, Rupert Öllinger, Roland Rad, Ulrike Protzer, Benedikt B. Kaufer, Robert J. Lebbink, Jan Rehwinkel, Trine H. Mogensen, Andreas Pichlmair
{"title":"Multi-proteomic profiling of the varicella-zoster virus–host interface reveals host susceptibilities to severe infection","authors":"Virginie Girault, Alexey Stukalov, Madalina Elena Carter-Timofte, Jonny Hertzog, Melissa Verin, Katharina Austen, Darya A. Haas, Lila Oubraham, Antonio Piras, Susanne Maidl, Rupert Öllinger, Roland Rad, Ulrike Protzer, Benedikt B. Kaufer, Robert J. Lebbink, Jan Rehwinkel, Trine H. Mogensen, Andreas Pichlmair","doi":"10.1038/s41564-025-02068-7","DOIUrl":"10.1038/s41564-025-02068-7","url":null,"abstract":"Varicella-zoster virus (VZV) infects most humans and causes chickenpox, shingles and central nervous system pathologies. The molecular basis for these phenotypes remains elusive. Here we conducted a multi-proteomic survey on 64 individual VZV proteins and infection-induced perturbations in a neuronal cell line, identifying 900 interactors and 3,618 regulated host proteins. Data integration suggested molecular functions of viral proteins, such as a mechanism for the ORF61-mediated IFI16 degradation via the recruitment of E3 ligase co-factors. Moreover, we identified proviral host factors (MPP8 and ZNF280D) as potential targets to limit infection. Integration of exome sequencing analysis from patients with VZV-associated central nervous system pathologies identified nephrocystin 4 as a viral restriction factor, and its S862N variant, which showed reduced activity and decreased binding to the regulatory proteins 14-3-3. Collectively, our study provides a comprehensive herpesvirus–host interface resource, which aids our understanding of disease-associated molecular perturbations and data-driven identification of antiviral treatment options. Proteomic characterization of varicella-zoster virus–host protein interactions and infection-induced changes in a neuronal cell line identifies potential targets for drug discovery and molecular insights into severe disease.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 8","pages":"2048-2072"},"PeriodicalIF":19.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02068-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737011","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}