Pub Date : 2025-12-04DOI: 10.1038/s41564-025-02206-1
Junyeong Ma, Nayeon Kim, Jun Hyung Cha, Wonjong Kim, Chan Yeong Kim, Yong-ho Lee, Han Sang Kim, Yoon Dae Han, Dongeun Yong, Eugene Han, Sunmo Yang, Samuel Beck, Insuk Lee
Understanding the human gut microbiome requires comprehensive genomic catalogues, yet many lack geographic diversity and contain medium-quality metagenome-assembled genomes (MAGs) missing up to 50% of genomic regions, potentially distorting functional insights. Here we describe an enhanced Human Reference Gut Microbiome (HRGM2) resource, a catalogue of near-complete MAGs (≥90% completeness, ≤5% contamination) and isolate genomes. HRGM2 comprises 155,211 non-redundant near-complete genomes from 4,824 prokaryotic species across 41 countries, representing a 66% increase in genome count and a 50% boost in species diversity compared to the Unified Human Gastrointestinal Genome catalogue. It enabled improved DNA-based species profiling, resolution of strain heterogeneity and survey of the human gut resistome. The exclusive use of these genomes improved metabolic capacity assessment, enabling high-confidence, automated genome-scale metabolic models of the entire microbiota and revealing disease-associated microbial metabolic interactions. This resource will facilitate reliable functional insights into gut microbiomes. HRGM2 is a catalogue of 155,211 high-quality metagenome-assembled genomes spanning 41 countries that allows improved genome-scale metabolic modelling and functional characterization of human gut microbes.
{"title":"A human gut metagenome-assembled genome catalogue spanning 41 countries supports genome-scale metabolic models","authors":"Junyeong Ma, Nayeon Kim, Jun Hyung Cha, Wonjong Kim, Chan Yeong Kim, Yong-ho Lee, Han Sang Kim, Yoon Dae Han, Dongeun Yong, Eugene Han, Sunmo Yang, Samuel Beck, Insuk Lee","doi":"10.1038/s41564-025-02206-1","DOIUrl":"10.1038/s41564-025-02206-1","url":null,"abstract":"Understanding the human gut microbiome requires comprehensive genomic catalogues, yet many lack geographic diversity and contain medium-quality metagenome-assembled genomes (MAGs) missing up to 50% of genomic regions, potentially distorting functional insights. Here we describe an enhanced Human Reference Gut Microbiome (HRGM2) resource, a catalogue of near-complete MAGs (≥90% completeness, ≤5% contamination) and isolate genomes. HRGM2 comprises 155,211 non-redundant near-complete genomes from 4,824 prokaryotic species across 41 countries, representing a 66% increase in genome count and a 50% boost in species diversity compared to the Unified Human Gastrointestinal Genome catalogue. It enabled improved DNA-based species profiling, resolution of strain heterogeneity and survey of the human gut resistome. The exclusive use of these genomes improved metabolic capacity assessment, enabling high-confidence, automated genome-scale metabolic models of the entire microbiota and revealing disease-associated microbial metabolic interactions. This resource will facilitate reliable functional insights into gut microbiomes. HRGM2 is a catalogue of 155,211 high-quality metagenome-assembled genomes spanning 41 countries that allows improved genome-scale metabolic modelling and functional characterization of human gut microbes.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"317-334"},"PeriodicalIF":19.4,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664478","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}
Pub Date : 2025-12-04DOI: 10.1038/s41564-025-02202-5
Marion Urvoy, Cristina Howard-Varona, Carlos Owusu-Ansah, Andrew J. Stai, John A. Bouranis, Marie Burris, Natalie Solonenko, Robert L. Hettich, Karin Holmfeldt, Malak M. Tfaily, Karna Gowda, Matthew B. Sullivan
Phage–bacteria interactions shape ecology and biogeochemistry across biomes. Resistance, arising from their evolutionary arms race, is well documented for receptor mutations, but other resistance mechanisms and their ecological implications remain unexplored. Here we isolated, sequenced and characterized 13 phage-resistant mutants of marine Cellulophaga baltica (Flavobacteriia). Mechanistically, mutations in surface proteins provided broad and complete extracellular resistance against multiple phages through decreased adsorption. Intracellular mutations affecting serine, glycine and threonine metabolism produced narrower resistance against a single phage, permitting viral DNA replication, and, in one mutant, were shown to be lipid mediated. Putative ecosystem impacts inferred from in vitro experiments include: (1) altered carbon utilization for all mutants, but especially by surface ones, (2) increased metabolite secretion for one modelled intracellular mutant (including experimentally verified acetate) and (3) increased ‘stickiness’ for all mutants, with surface mutants also sedimenting faster. Our findings highlight new resistance mechanisms and suggest that the phage–host arms race could result in ecosystem-level biogeochemical impacts in marine microorganisms. Evading infection in Cellulophaga baltica comes with cellular changes that alter carbon cycling, metabolite secretion and sedimentation rates.
{"title":"Phage resistance mutations in a marine bacterium impact biogeochemically relevant cellular processes","authors":"Marion Urvoy, Cristina Howard-Varona, Carlos Owusu-Ansah, Andrew J. Stai, John A. Bouranis, Marie Burris, Natalie Solonenko, Robert L. Hettich, Karin Holmfeldt, Malak M. Tfaily, Karna Gowda, Matthew B. Sullivan","doi":"10.1038/s41564-025-02202-5","DOIUrl":"10.1038/s41564-025-02202-5","url":null,"abstract":"Phage–bacteria interactions shape ecology and biogeochemistry across biomes. Resistance, arising from their evolutionary arms race, is well documented for receptor mutations, but other resistance mechanisms and their ecological implications remain unexplored. Here we isolated, sequenced and characterized 13 phage-resistant mutants of marine Cellulophaga baltica (Flavobacteriia). Mechanistically, mutations in surface proteins provided broad and complete extracellular resistance against multiple phages through decreased adsorption. Intracellular mutations affecting serine, glycine and threonine metabolism produced narrower resistance against a single phage, permitting viral DNA replication, and, in one mutant, were shown to be lipid mediated. Putative ecosystem impacts inferred from in vitro experiments include: (1) altered carbon utilization for all mutants, but especially by surface ones, (2) increased metabolite secretion for one modelled intracellular mutant (including experimentally verified acetate) and (3) increased ‘stickiness’ for all mutants, with surface mutants also sedimenting faster. Our findings highlight new resistance mechanisms and suggest that the phage–host arms race could result in ecosystem-level biogeochemical impacts in marine microorganisms. Evading infection in Cellulophaga baltica comes with cellular changes that alter carbon cycling, metabolite secretion and sedimentation rates.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"195-210"},"PeriodicalIF":19.4,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664477","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}
Pub Date : 2025-12-03DOI: 10.1038/s41564-025-02197-z
Lu Zhang, Andrea Marfil-Sánchez, Ting-Hao Kuo, Bastian Seelbinder, Loes van Dam, Ana Depetris-Chauvin, Leonie Johanna Jahn, Morten O. A. Sommer, Michael Zimmermann, Yueqiong Ni, Gianni Panagiotou
Food, especially plant-based diet, has complex chemical diversity. However, large-scale phytonutrient-metabolizing activities of gut bacteria are largely unknown. Here we integrated and systematically analysed multiple databases containing information on enzymatic reactions and food health benefits, and 3,068 global public human microbiomes. Transformation of 775 phytonutrients from edible plants was associated with enzymes encoded by diverse gut microbes. In vitro assays validated the biotransformation activity of gut species, for example, Eubacterium ramulus. The biotransformation of phytonutrients demonstrated high interpersonal and geographical variability. Machine learning models based on 2,486 public case–control microbiomes, using the abundances of enzymes associated with modification of phytonutrients present in health-associated foods, discriminated the health status of individuals in multiple disease contexts, suggesting altered biotransformation potential in disease. We validated the association of microbiome-encoded enzymes with the anti-inflammatory activity of common edible plants by combining metagenomics and metatranscriptomics analysis in specific-pathogen-free and germ-free mice. These findings have implications for designing precise, personalized diets to guide an individual towards a healthy state. Systematic analysis and machine learning coupled with in vitro and in vivo validation link gut microbiome-mediated transformation of dietary phytonutrients to health outcomes.
{"title":"Gut microbiome-mediated transformation of dietary phytonutrients is associated with health outcomes","authors":"Lu Zhang, Andrea Marfil-Sánchez, Ting-Hao Kuo, Bastian Seelbinder, Loes van Dam, Ana Depetris-Chauvin, Leonie Johanna Jahn, Morten O. A. Sommer, Michael Zimmermann, Yueqiong Ni, Gianni Panagiotou","doi":"10.1038/s41564-025-02197-z","DOIUrl":"10.1038/s41564-025-02197-z","url":null,"abstract":"Food, especially plant-based diet, has complex chemical diversity. However, large-scale phytonutrient-metabolizing activities of gut bacteria are largely unknown. Here we integrated and systematically analysed multiple databases containing information on enzymatic reactions and food health benefits, and 3,068 global public human microbiomes. Transformation of 775 phytonutrients from edible plants was associated with enzymes encoded by diverse gut microbes. In vitro assays validated the biotransformation activity of gut species, for example, Eubacterium ramulus. The biotransformation of phytonutrients demonstrated high interpersonal and geographical variability. Machine learning models based on 2,486 public case–control microbiomes, using the abundances of enzymes associated with modification of phytonutrients present in health-associated foods, discriminated the health status of individuals in multiple disease contexts, suggesting altered biotransformation potential in disease. We validated the association of microbiome-encoded enzymes with the anti-inflammatory activity of common edible plants by combining metagenomics and metatranscriptomics analysis in specific-pathogen-free and germ-free mice. These findings have implications for designing precise, personalized diets to guide an individual towards a healthy state. Systematic analysis and machine learning coupled with in vitro and in vivo validation link gut microbiome-mediated transformation of dietary phytonutrients to health outcomes.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"94-110"},"PeriodicalIF":19.4,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02197-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664340","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}
Pub Date : 2025-12-03DOI: 10.1038/s41564-025-02201-6
Barbara Bosch, Vanisha Munsamy-Govender, Jansy Sarathy, Mirjana Lilic, Paul Dominic B. Olinares, Kathryn A. Eckartt, Pranav Nalam, Markus Lang, Marcell Simon, Adrian Richter, Jeremy M. Rock, Elizabeth A. Campbell
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, remains the deadliest human pathogen. Treatment is hampered by drug resistance and the persistence of slow-growing or non-replicating populations. Rifampicin, a cornerstone of first-line therapy, inhibits transcription during promoter escape, but resistance mutations undermine efficacy and drive resistance spread. We revisited the transcription cycle as an antibacterial target by characterizing AAP-SO2, an RNA polymerase inhibitor with whole-cell activity against Mtb. AAP-SO2 slows the nucleotide addition cycle, disrupting elongation and termination. Rifampicin-resistant mutations impose fitness costs by perturbing the balance of these steps, creating exploitable weaknesses. Inhibition of transcription with AAP-SO2 reduced the evolution of rifampicin resistance and was especially effective against the most common resistant mutant. Combination treatment with rifampicin and AAP-SO2 synergistically killed non-replicating Mtb in an ex vivo rabbit granuloma model. These findings show that exploiting functional vulnerabilities of the transcription cycle can counter rifampicin resistance and improve clearance of recalcitrant Mtb populations. Targeting two distinct steps of the transcription process yields synergistic antibiotics that kill non-replicating Mycobacterium tuberculosis and reduce drug resistance.
{"title":"Transcription co-inhibition alters drug resistance evolution and enhances Mycobacterium tuberculosis clearance from granulomas","authors":"Barbara Bosch, Vanisha Munsamy-Govender, Jansy Sarathy, Mirjana Lilic, Paul Dominic B. Olinares, Kathryn A. Eckartt, Pranav Nalam, Markus Lang, Marcell Simon, Adrian Richter, Jeremy M. Rock, Elizabeth A. Campbell","doi":"10.1038/s41564-025-02201-6","DOIUrl":"10.1038/s41564-025-02201-6","url":null,"abstract":"Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, remains the deadliest human pathogen. Treatment is hampered by drug resistance and the persistence of slow-growing or non-replicating populations. Rifampicin, a cornerstone of first-line therapy, inhibits transcription during promoter escape, but resistance mutations undermine efficacy and drive resistance spread. We revisited the transcription cycle as an antibacterial target by characterizing AAP-SO2, an RNA polymerase inhibitor with whole-cell activity against Mtb. AAP-SO2 slows the nucleotide addition cycle, disrupting elongation and termination. Rifampicin-resistant mutations impose fitness costs by perturbing the balance of these steps, creating exploitable weaknesses. Inhibition of transcription with AAP-SO2 reduced the evolution of rifampicin resistance and was especially effective against the most common resistant mutant. Combination treatment with rifampicin and AAP-SO2 synergistically killed non-replicating Mtb in an ex vivo rabbit granuloma model. These findings show that exploiting functional vulnerabilities of the transcription cycle can counter rifampicin resistance and improve clearance of recalcitrant Mtb populations. Targeting two distinct steps of the transcription process yields synergistic antibiotics that kill non-replicating Mycobacterium tuberculosis and reduce drug resistance.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"180-194"},"PeriodicalIF":19.4,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664341","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}
Pub Date : 2025-12-01DOI: 10.1038/s41564-025-02211-4
We uncover hundreds of inhibitory interactions between industrial and agricultural chemicals and gut bacteria. Systematic genetic analyses reveal bacterial survival mechanisms against pollutants and their commonality with antibiotic resistance. Our data enable machine learning-based predictive toxicology and make a case for considering antibacterial activity in chemical safety assessment.
{"title":"Common chemical pollutants inhibit human gut bacteria","authors":"","doi":"10.1038/s41564-025-02211-4","DOIUrl":"10.1038/s41564-025-02211-4","url":null,"abstract":"We uncover hundreds of inhibitory interactions between industrial and agricultural chemicals and gut bacteria. Systematic genetic analyses reveal bacterial survival mechanisms against pollutants and their commonality with antibiotic resistance. Our data enable machine learning-based predictive toxicology and make a case for considering antibacterial activity in chemical safety assessment.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 12","pages":"3047-3048"},"PeriodicalIF":19.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645165","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}
Pub Date : 2025-12-01DOI: 10.1038/s41564-025-02221-2
A new community-led checklist provides reporting guidelines for microbiome research across environments.
一个新的社区主导的清单为跨环境的微生物组研究提供了报告指南。
{"title":"STREAM-lining guidelines for microbiome research","authors":"","doi":"10.1038/s41564-025-02221-2","DOIUrl":"10.1038/s41564-025-02221-2","url":null,"abstract":"A new community-led checklist provides reporting guidelines for microbiome research across environments.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 12","pages":"3041-3042"},"PeriodicalIF":19.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02221-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145646815","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}
Pub Date : 2025-12-01DOI: 10.1038/s41564-025-02186-2
Julia M. Kelliher, Chloe Mirzayi, Sarah R. Bordenstein, Aaron Oliver, Christina A. Kellogg, Eneida L. Hatcher, Maureen Berg, Petr Baldrian, Mashael Aljumaah, Cassandra Maria Luz Miller, Christopher Mungall, Vlastimil Novak, Alexis Palucki, Ethan Smith, Nazifa Tabassum, Gregory Bonito, J. Rodney Brister, Patrick S. G. Chain, Mingfei Chen, Samuel Degregori, Jose Pablo Dundore-Arias, Joanne B. Emerson, Vanessa Moreira C. Fernandes, Roberto Flores, Antonio Gonzalez, Zoe A. Hansen, Scott A. Jackson, Ahmed M. Moustafa, Trent R. Northen, Nonia Pariente, Jennifer Pett-Ridge, Sydne Record, Linta Reji, Anna-Louise Reysenbach, Virginia I. Rich, Lorna Richardson, Simon Roux, Lynn M. Schriml, Reed S. Shabman, Maria A. Sierra, Matthew B. Sullivan, Punithavathi Sundaramurthy, Katherine M. Thibault, Luke R. Thompson, Scott Tighe, Ethell Vereen, STREAMS Consortium, Emiley A. Eloe-Fadrosh
The interdisciplinary nature of microbiome research, coupled with the generation of complex multi-omics data, makes knowledge sharing challenging. The Strengthening the Organization and Reporting of Microbiome Studies (STORMS) guidelines provide a checklist for the reporting of study information, experimental design and analytical methods within a scientific manuscript on human microbiome research. Here, in this Consensus Statement, we present the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines. The guidelines expand on STORMS and include 67 items to support the reporting and review of environmental (for example, terrestrial, aquatic, atmospheric and engineered), synthetic and non-human host-associated microbiome studies in a standardized and machine-actionable manner. Based on input from 248 researchers spanning 28 countries, we provide detailed guidance, including comparisons with STORMS, and case studies that demonstrate the usage of the STREAMS guidelines. STREAMS, like STORMS, will be a living community resource updated by the Consortium with consensus-building input of the broader community. This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.
{"title":"STREAMS guidelines: standards for technical reporting in environmental and host-associated microbiome studies","authors":"Julia M. Kelliher, Chloe Mirzayi, Sarah R. Bordenstein, Aaron Oliver, Christina A. Kellogg, Eneida L. Hatcher, Maureen Berg, Petr Baldrian, Mashael Aljumaah, Cassandra Maria Luz Miller, Christopher Mungall, Vlastimil Novak, Alexis Palucki, Ethan Smith, Nazifa Tabassum, Gregory Bonito, J. Rodney Brister, Patrick S. G. Chain, Mingfei Chen, Samuel Degregori, Jose Pablo Dundore-Arias, Joanne B. Emerson, Vanessa Moreira C. Fernandes, Roberto Flores, Antonio Gonzalez, Zoe A. Hansen, Scott A. Jackson, Ahmed M. Moustafa, Trent R. Northen, Nonia Pariente, Jennifer Pett-Ridge, Sydne Record, Linta Reji, Anna-Louise Reysenbach, Virginia I. Rich, Lorna Richardson, Simon Roux, Lynn M. Schriml, Reed S. Shabman, Maria A. Sierra, Matthew B. Sullivan, Punithavathi Sundaramurthy, Katherine M. Thibault, Luke R. Thompson, Scott Tighe, Ethell Vereen, STREAMS Consortium, Emiley A. Eloe-Fadrosh","doi":"10.1038/s41564-025-02186-2","DOIUrl":"10.1038/s41564-025-02186-2","url":null,"abstract":"The interdisciplinary nature of microbiome research, coupled with the generation of complex multi-omics data, makes knowledge sharing challenging. The Strengthening the Organization and Reporting of Microbiome Studies (STORMS) guidelines provide a checklist for the reporting of study information, experimental design and analytical methods within a scientific manuscript on human microbiome research. Here, in this Consensus Statement, we present the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines. The guidelines expand on STORMS and include 67 items to support the reporting and review of environmental (for example, terrestrial, aquatic, atmospheric and engineered), synthetic and non-human host-associated microbiome studies in a standardized and machine-actionable manner. Based on input from 248 researchers spanning 28 countries, we provide detailed guidance, including comparisons with STORMS, and case studies that demonstrate the usage of the STREAMS guidelines. STREAMS, like STORMS, will be a living community resource updated by the Consortium with consensus-building input of the broader community. This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 12","pages":"3059-3068"},"PeriodicalIF":19.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02186-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145646816","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}
Pub Date : 2025-11-28DOI: 10.1038/s41564-025-02173-7
Samuel Pazicky, Seth Tjia, Guilherme B. Farias, Nick Piwon, Nisha Philip, Radoslaw M. Sobota, Andrew P. Waters, Tim-Wolf Gilberger, Zbynek Bozdech
The malaria parasite Plasmodium falciparum undergoes a complex intraerythrocytic developmental cycle (IDC) that relies on a dynamic network of protein–protein interactions. These are usually mapped ex vivo, limiting our understanding of their dynamics and composition in natural environments. Here we introduce the meltome-assisted profiling of protein complexes (MAP-X) that maps the complexome through thermal proteome profiling in intact cells. We applied MAP-X across seven timepoints in the P. falciparum IDC. MAP-X predicted more than 20,000 interactions, resolving conserved protein complexes, reproducing previously identified interactions and finding previously unreported associations. We found that malaria protein complexes undergo distinct dynamic alterations, and we predicted their moonlighting subunits that dissociate from their native complex to assume different biological functions. Altogether, our findings provide a resource for uncovering Plasmodium biology and show that MAP-X can characterize protein complexes in intact cells to reveal cellular physiology at a proteome-wide level. MAP-X is used to map protein complexes in P. falciparum, identifying previously undescribed interactions, revealing stage-specific dynamics and predicting moonlighting behaviour of subunits.
疟疾寄生虫恶性疟原虫经历一个复杂的红细胞内发育周期（IDC），依赖于蛋白质-蛋白质相互作用的动态网络。这些通常是在体外绘制的，限制了我们对它们在自然环境中的动态和组成的理解。在这里，我们介绍了meltome-assisted profiling of protein complexes (MAP-X)，它通过在完整细胞中的热蛋白质组分析来绘制络合物。我们将MAP-X应用于恶性疟原虫IDC的7个时间点。MAP-X预测了超过20,000种相互作用，分解了保守的蛋白质复合物，重现了以前确定的相互作用，并发现了以前未报道的关联。我们发现疟疾蛋白复合物经历了不同的动态变化，我们预测了它们的兼职亚基，这些亚基与它们的天然复合物分离，承担不同的生物学功能。总之，我们的研究结果为揭示疟原虫生物学提供了资源，并表明MAP-X可以表征完整细胞中的蛋白质复合物，从而在蛋白质组水平上揭示细胞生理学。map - x用于绘制恶性疟原虫的蛋白质复合物，识别以前未描述的相互作用，揭示特定阶段的动力学并预测亚单位的兼职行为。
{"title":"MAP-X reveals distinct protein complex dynamics across Plasmodium falciparum blood stages","authors":"Samuel Pazicky, Seth Tjia, Guilherme B. Farias, Nick Piwon, Nisha Philip, Radoslaw M. Sobota, Andrew P. Waters, Tim-Wolf Gilberger, Zbynek Bozdech","doi":"10.1038/s41564-025-02173-7","DOIUrl":"10.1038/s41564-025-02173-7","url":null,"abstract":"The malaria parasite Plasmodium falciparum undergoes a complex intraerythrocytic developmental cycle (IDC) that relies on a dynamic network of protein–protein interactions. These are usually mapped ex vivo, limiting our understanding of their dynamics and composition in natural environments. Here we introduce the meltome-assisted profiling of protein complexes (MAP-X) that maps the complexome through thermal proteome profiling in intact cells. We applied MAP-X across seven timepoints in the P. falciparum IDC. MAP-X predicted more than 20,000 interactions, resolving conserved protein complexes, reproducing previously identified interactions and finding previously unreported associations. We found that malaria protein complexes undergo distinct dynamic alterations, and we predicted their moonlighting subunits that dissociate from their native complex to assume different biological functions. Altogether, our findings provide a resource for uncovering Plasmodium biology and show that MAP-X can characterize protein complexes in intact cells to reveal cellular physiology at a proteome-wide level. MAP-X is used to map protein complexes in P. falciparum, identifying previously undescribed interactions, revealing stage-specific dynamics and predicting moonlighting behaviour of subunits.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 12","pages":"3229-3244"},"PeriodicalIF":19.4,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611575","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}
Pub Date : 2025-11-28DOI: 10.1038/s41564-025-02190-6
Sofia Medvedeva, Ulysse Guyet, Eric Pelletier, Hans-Joachim Ruscheweyh, Shinichi Sunagawa, Hiroyuki Ogata, Frank O. Aylward, Morgan Gaïa, Natalya Yutin, Eugene V. Koonin, Mart Krupovic, Tom O. Delmont
Mirusviruses infect unicellular eukaryotes and are related to tailed bacteriophages and herpesviruses. Here we expand the known diversity of mirusviruses by screening diverse metagenomic assemblies and characterizing 1,202 non-redundant environmental genomes. Mirusviricota comprises a highly diversified phylum of large and giant eukaryotic viruses that rivals the evolutionary scope and functional complexity of nucleocytoviruses. Critically, major Mirusviricota lineages lack essential genes encoding components of the replication and transcription machineries and, concomitantly, encompass numerous spliceosomal introns that are enriched in virion morphogenesis genes. These features point to multiple transitions from cytoplasmic to nuclear reproduction during mirusvirus evolution. Many mirusvirus introns encode diverse homing endonucleases, suggestive of a previously undescribed mechanism promoting the horizontal mobility of spliceosomal introns. Available metatranscriptomes reveal long-range trans-splicing in a virion morphogenesis gene. Collectively, our data strongly suggest that nuclei of unicellular eukaryotes across marine and freshwater ecosystems worldwide are a major niche for replication of intron-rich mirusviruses. Environmental metagenomic explorations show that Mirusviricota lineages lack essential replication and transcription genes and contain spliceosomal introns, suggesting nuclear reproduction.
{"title":"Widespread and intron-rich mirusviruses are predicted to reproduce in nuclei of unicellular eukaryotes","authors":"Sofia Medvedeva, Ulysse Guyet, Eric Pelletier, Hans-Joachim Ruscheweyh, Shinichi Sunagawa, Hiroyuki Ogata, Frank O. Aylward, Morgan Gaïa, Natalya Yutin, Eugene V. Koonin, Mart Krupovic, Tom O. Delmont","doi":"10.1038/s41564-025-02190-6","DOIUrl":"10.1038/s41564-025-02190-6","url":null,"abstract":"Mirusviruses infect unicellular eukaryotes and are related to tailed bacteriophages and herpesviruses. Here we expand the known diversity of mirusviruses by screening diverse metagenomic assemblies and characterizing 1,202 non-redundant environmental genomes. Mirusviricota comprises a highly diversified phylum of large and giant eukaryotic viruses that rivals the evolutionary scope and functional complexity of nucleocytoviruses. Critically, major Mirusviricota lineages lack essential genes encoding components of the replication and transcription machineries and, concomitantly, encompass numerous spliceosomal introns that are enriched in virion morphogenesis genes. These features point to multiple transitions from cytoplasmic to nuclear reproduction during mirusvirus evolution. Many mirusvirus introns encode diverse homing endonucleases, suggestive of a previously undescribed mechanism promoting the horizontal mobility of spliceosomal introns. Available metatranscriptomes reveal long-range trans-splicing in a virion morphogenesis gene. Collectively, our data strongly suggest that nuclei of unicellular eukaryotes across marine and freshwater ecosystems worldwide are a major niche for replication of intron-rich mirusviruses. Environmental metagenomic explorations show that Mirusviricota lineages lack essential replication and transcription genes and contain spliceosomal introns, suggesting nuclear reproduction.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"228-239"},"PeriodicalIF":19.4,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02190-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611571","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}
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