Pub Date : 2025-01-27DOI: 10.1038/s41564-025-01927-7
Landon J. Getz, Sam R. Fairburn, Y. Vivian Liu, Amy L. Qian, Karen L. Maxwell
Bacterial genomes have regions known as defence islands that encode diverse systems to protect against phage infection. Although genetic elements that capture and store gene cassettes in Vibrio species, called integrons, are known to play an important role in bacterial adaptation, a role in phage defence had not been defined. Here we combine bioinformatic and molecular techniques to show that the chromosomal integron of Vibrio parahaemolyticus is a hotspot for anti-phage defence genes. Using bioinformatics, we discovered that previously characterized defences localize to integrons. Intrigued by this discovery, we cloned 57 integron gene cassettes and identified 9 previously unrecognized systems that mediate defence. Our work reveals that integrons are an important reservoir of defence systems in V. parahaemolyticus. As integrons are of ancient origin and are widely distributed among Proteobacteria, these results provide an approach for the discovery of anti-phage defence systems across a broad range of bacteria.
{"title":"Integrons are anti-phage defence libraries in Vibrio parahaemolyticus","authors":"Landon J. Getz, Sam R. Fairburn, Y. Vivian Liu, Amy L. Qian, Karen L. Maxwell","doi":"10.1038/s41564-025-01927-7","DOIUrl":"https://doi.org/10.1038/s41564-025-01927-7","url":null,"abstract":"<p>Bacterial genomes have regions known as defence islands that encode diverse systems to protect against phage infection. Although genetic elements that capture and store gene cassettes in <i>Vibrio</i> species, called integrons, are known to play an important role in bacterial adaptation, a role in phage defence had not been defined. Here we combine bioinformatic and molecular techniques to show that the chromosomal integron of <i>Vibrio parahaemolyticus</i> is a hotspot for anti-phage defence genes. Using bioinformatics, we discovered that previously characterized defences localize to integrons. Intrigued by this discovery, we cloned 57 integron gene cassettes and identified 9 previously unrecognized systems that mediate defence. Our work reveals that integrons are an important reservoir of defence systems in <i>V. parahaemolyticus</i>. As integrons are of ancient origin and are widely distributed among Proteobacteria, these results provide an approach for the discovery of anti-phage defence systems across a broad range of bacteria.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"4 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044071","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 : 2025-01-24DOI: 10.1038/s41564-024-01906-4
Michael J. Tisza, Richard E. Lloyd, Kristi Hoffman, Daniel P. Smith, Marian Rewers, Sara J. Javornik Cregeen, Joseph F. Petrosino
Microbial colonization of the human gut occurs soon after birth, proceeds through well-studied phases and is affected by lifestyle and other factors. Less is known about phage community dynamics during infant gut colonization due to small study sizes, an inability to leverage large databases and a lack of appropriate bioinformatics tools. Here we reanalysed whole microbial community shotgun sequencing data of 12,262 longitudinal samples from 887 children from four countries across four years of life as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We developed an extensive metagenome-assembled genome catalogue using the Marker-MAGu pipeline, which comprised 49,111 phage taxa from existing human microbiome datasets. This was used to identify phage marker genes and their integration into the MetaPhlAn 4 bacterial marker gene database enabled simultaneous assessment of phage and bacterial dynamics. We found that individual children are colonized by hundreds of different phages, which are more transitory than bacteria, accumulating a more diverse phage community over time. Type 1 diabetes correlated with a decreased rate of change in bacterial and viral communities in children aged one and two. The addition of phage data improved the ability of machine learning models to discriminate samples by country. Finally, although phage populations were specific to individuals, we observed trends of phage ecological succession that correlated well with putative host bacteria. This resource improves our understanding of phage–bacteria interactions in the developing early life microbiome. Reanalysis of 12,262 longitudinal infant gut microbiome samples using the Marker-MAGu pipeline revealed phage–bacteria dynamics over the first year of life.
{"title":"Longitudinal phage–bacteria dynamics in the early life gut microbiome","authors":"Michael J. Tisza, Richard E. Lloyd, Kristi Hoffman, Daniel P. Smith, Marian Rewers, Sara J. Javornik Cregeen, Joseph F. Petrosino","doi":"10.1038/s41564-024-01906-4","DOIUrl":"10.1038/s41564-024-01906-4","url":null,"abstract":"Microbial colonization of the human gut occurs soon after birth, proceeds through well-studied phases and is affected by lifestyle and other factors. Less is known about phage community dynamics during infant gut colonization due to small study sizes, an inability to leverage large databases and a lack of appropriate bioinformatics tools. Here we reanalysed whole microbial community shotgun sequencing data of 12,262 longitudinal samples from 887 children from four countries across four years of life as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We developed an extensive metagenome-assembled genome catalogue using the Marker-MAGu pipeline, which comprised 49,111 phage taxa from existing human microbiome datasets. This was used to identify phage marker genes and their integration into the MetaPhlAn 4 bacterial marker gene database enabled simultaneous assessment of phage and bacterial dynamics. We found that individual children are colonized by hundreds of different phages, which are more transitory than bacteria, accumulating a more diverse phage community over time. Type 1 diabetes correlated with a decreased rate of change in bacterial and viral communities in children aged one and two. The addition of phage data improved the ability of machine learning models to discriminate samples by country. Finally, although phage populations were specific to individuals, we observed trends of phage ecological succession that correlated well with putative host bacteria. This resource improves our understanding of phage–bacteria interactions in the developing early life microbiome. Reanalysis of 12,262 longitudinal infant gut microbiome samples using the Marker-MAGu pipeline revealed phage–bacteria dynamics over the first year of life.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"420-430"},"PeriodicalIF":20.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01906-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026713","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 : 2025-01-24DOI: 10.1038/s41564-024-01919-z
Jeremie Alexander, Gary Liu, Jonathan M. Stokes
An explainable deep learning model enables the identification and virtual optimization of antimicrobial peptides (AMPs) from the oral microbiome, yielding novel AMPs with activity against ESKAPE pathogens and demonstrating efficacy in a mouse wound infection model.
{"title":"Explainable artificial intelligence evolves antimicrobial peptides","authors":"Jeremie Alexander, Gary Liu, Jonathan M. Stokes","doi":"10.1038/s41564-024-01919-z","DOIUrl":"10.1038/s41564-024-01919-z","url":null,"abstract":"An explainable deep learning model enables the identification and virtual optimization of antimicrobial peptides (AMPs) from the oral microbiome, yielding novel AMPs with activity against ESKAPE pathogens and demonstrating efficacy in a mouse wound infection model.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"267-269"},"PeriodicalIF":20.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026398","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}
A Bacteroides vulgatus metabolite, pantothenate, induces secretion of the hormones GLP1 in the gut and FGF21 in the liver, which act on the hypothalamus to reduce sugar intake.
{"title":"A gut microorganism turns the dial on sugar intake","authors":"Clémence Fayt, Nuria Morales-Puerto, Amandine Everard","doi":"10.1038/s41564-024-01917-1","DOIUrl":"10.1038/s41564-024-01917-1","url":null,"abstract":"A Bacteroides vulgatus metabolite, pantothenate, induces secretion of the hormones GLP1 in the gut and FGF21 in the liver, which act on the hypothalamus to reduce sugar intake.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"270-271"},"PeriodicalIF":20.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026399","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 : 2025-01-24DOI: 10.1038/s41564-024-01920-6
Douglas E. Johnson, Roshonda B. Jones
{"title":"Predicting child health with gut microbiome development trajectories","authors":"Douglas E. Johnson, Roshonda B. Jones","doi":"10.1038/s41564-024-01920-6","DOIUrl":"10.1038/s41564-024-01920-6","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"265-266"},"PeriodicalIF":20.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026604","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 : 2025-01-23DOI: 10.1038/s41564-024-01921-5
Yeranddy A. Alpizar, Kai Dallmeier
Vaccine-induced neutralizing antibodies are widely considered sufficient and required for protection from yellow fever and related viral infections. Emerging evidence shows how cellular immunity may compensate for a lack in appropriate humoral responses.
{"title":"T cell-mediated protection in absence of virus neutralizing antibodies","authors":"Yeranddy A. Alpizar, Kai Dallmeier","doi":"10.1038/s41564-024-01921-5","DOIUrl":"10.1038/s41564-024-01921-5","url":null,"abstract":"Vaccine-induced neutralizing antibodies are widely considered sufficient and required for protection from yellow fever and related viral infections. Emerging evidence shows how cellular immunity may compensate for a lack in appropriate humoral responses.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"277-278"},"PeriodicalIF":20.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020618","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 : 2025-01-23DOI: 10.1038/s41564-024-01904-6
Romana Vargová, Roxanne Chevreau, Marine Alves, Camille Courbin, Kara Terry, Pierre Legrand, Marek Eliáš, Julie Ménétrey, Joel B. Dacks, Catherine L. Jackson
The evolution of eukaryotes is a fundamental event in the history of life. The closest prokaryotic lineage to eukaryotes, the Asgardarchaeota, encode proteins previously found only in eukaryotes, providing insight into their archaeal ancestor. Eukaryotic cells are characterized by endomembrane organelles, and the Arf family GTPases regulate organelle dynamics by recruiting effector proteins to membranes upon activation. The Arf family is ubiquitous among eukaryotes, but its origins remain elusive. Here we report a group of prokaryotic GTPases, the ArfRs, which are widely present in Asgardarchaeota. Phylogenetic analyses reveal that eukaryotic Arf family proteins arose from the ArfR group. Expression of representative Asgardarchaeota ArfR proteins in yeast and X-ray crystallographic studies show that ArfR GTPases possess the mechanism of membrane binding and structural features unique to Arf family proteins. Our results indicate that Arf family GTPases originated in the archaeal ancestor of eukaryotes, consistent with aspects of the endomembrane system evolving early in eukaryogenesis. Eukaryotic Arf family proteins involved in endomembrane organelle dynamics arose from the Asgard archaeal ArfR GTPases, indicating this capability likely originated in the archaeal ancestor of eukaryotes.
{"title":"The Asgard archaeal origins of Arf family GTPases involved in eukaryotic organelle dynamics","authors":"Romana Vargová, Roxanne Chevreau, Marine Alves, Camille Courbin, Kara Terry, Pierre Legrand, Marek Eliáš, Julie Ménétrey, Joel B. Dacks, Catherine L. Jackson","doi":"10.1038/s41564-024-01904-6","DOIUrl":"10.1038/s41564-024-01904-6","url":null,"abstract":"The evolution of eukaryotes is a fundamental event in the history of life. The closest prokaryotic lineage to eukaryotes, the Asgardarchaeota, encode proteins previously found only in eukaryotes, providing insight into their archaeal ancestor. Eukaryotic cells are characterized by endomembrane organelles, and the Arf family GTPases regulate organelle dynamics by recruiting effector proteins to membranes upon activation. The Arf family is ubiquitous among eukaryotes, but its origins remain elusive. Here we report a group of prokaryotic GTPases, the ArfRs, which are widely present in Asgardarchaeota. Phylogenetic analyses reveal that eukaryotic Arf family proteins arose from the ArfR group. Expression of representative Asgardarchaeota ArfR proteins in yeast and X-ray crystallographic studies show that ArfR GTPases possess the mechanism of membrane binding and structural features unique to Arf family proteins. Our results indicate that Arf family GTPases originated in the archaeal ancestor of eukaryotes, consistent with aspects of the endomembrane system evolving early in eukaryogenesis. Eukaryotic Arf family proteins involved in endomembrane organelle dynamics arose from the Asgard archaeal ArfR GTPases, indicating this capability likely originated in the archaeal ancestor of eukaryotes.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"495-508"},"PeriodicalIF":20.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020842","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 : 2025-01-23DOI: 10.1038/s41564-024-01915-3
Thomas C. McLean, Francisco Balaguer-Pérez, Joshua Chandanani, Christopher M. Thomas, Clara Aicart-Ramos, Sophia Burick, Paul Dominic B. Olinares, Giulia Gobbato, Julia E. A. Mundy, Brian T. Chait, David M. Lawson, Seth A. Darst, Elizabeth A. Campbell, Fernando Moreno-Herrero, Tung B. K. Le
Examples of long-range gene regulation in bacteria are rare and generally thought to involve DNA looping. Here, using a combination of biophysical approaches including X-ray crystallography and single-molecule analysis for the KorB–KorA system in Escherichia coli, we show that long-range gene silencing on the plasmid RK2, a source of multi-drug resistance across diverse Gram-negative bacteria, is achieved cooperatively by a DNA-sliding clamp, KorB, and a clamp-locking protein, KorA. We show that KorB is a CTPase clamp that can entrap and slide along DNA to reach distal target promoters up to 1.5 kb away. We resolved the tripartite crystal structure of a KorB–KorA–DNA co-complex, revealing that KorA latches KorB into a closed clamp state. DNA-bound KorA thus stimulates repression by stalling KorB sliding at target promoters to occlude RNA polymerase holoenzymes. Together, our findings explain the mechanistic basis for KorB role switching from a DNA-sliding clamp to a co-repressor and provide an alternative mechanism for long-range regulation of gene expression in bacteria. Structural and single-molecule analyses show the CTPase, KorB, is a sliding DNA clamp that interacts with a clamp-locking protein KorA to inhibit gene expression over distances of more than 1 kb in the multi-drug resistance RK2 plasmid.
细菌中远程基因调控的例子很少，通常认为与DNA环有关。在这里，我们结合使用生物物理方法，包括x射线晶体学和对大肠杆菌KorB - KorA系统的单分子分析，我们发现质粒RK2上的远程基因沉默是由dna滑动夹（KorB）和夹锁蛋白（KorA）共同实现的，RK2是多种革兰氏阴性菌的多药耐药来源。我们发现KorB是一种CTPase夹子，可以捕获并沿着DNA滑动，到达最远1.5 kb的远端目标启动子。我们解析了KorB - KorA - dna共络合物的三方晶体结构，揭示了KorA将KorB锁存为闭合箝位状态。因此，dna结合的KorA通过阻止KorB在目标启动子处滑动以阻断RNA聚合酶全酶来刺激抑制。总之，我们的发现解释了KorB角色从dna滑动钳转换为协同抑制因子的机制基础，并为细菌中基因表达的远程调控提供了另一种机制。
{"title":"KorB switching from DNA-sliding clamp to repressor mediates long-range gene silencing in a multi-drug resistance plasmid","authors":"Thomas C. McLean, Francisco Balaguer-Pérez, Joshua Chandanani, Christopher M. Thomas, Clara Aicart-Ramos, Sophia Burick, Paul Dominic B. Olinares, Giulia Gobbato, Julia E. A. Mundy, Brian T. Chait, David M. Lawson, Seth A. Darst, Elizabeth A. Campbell, Fernando Moreno-Herrero, Tung B. K. Le","doi":"10.1038/s41564-024-01915-3","DOIUrl":"10.1038/s41564-024-01915-3","url":null,"abstract":"Examples of long-range gene regulation in bacteria are rare and generally thought to involve DNA looping. Here, using a combination of biophysical approaches including X-ray crystallography and single-molecule analysis for the KorB–KorA system in Escherichia coli, we show that long-range gene silencing on the plasmid RK2, a source of multi-drug resistance across diverse Gram-negative bacteria, is achieved cooperatively by a DNA-sliding clamp, KorB, and a clamp-locking protein, KorA. We show that KorB is a CTPase clamp that can entrap and slide along DNA to reach distal target promoters up to 1.5 kb away. We resolved the tripartite crystal structure of a KorB–KorA–DNA co-complex, revealing that KorA latches KorB into a closed clamp state. DNA-bound KorA thus stimulates repression by stalling KorB sliding at target promoters to occlude RNA polymerase holoenzymes. Together, our findings explain the mechanistic basis for KorB role switching from a DNA-sliding clamp to a co-repressor and provide an alternative mechanism for long-range regulation of gene expression in bacteria. Structural and single-molecule analyses show the CTPase, KorB, is a sliding DNA clamp that interacts with a clamp-locking protein KorA to inhibit gene expression over distances of more than 1 kb in the multi-drug resistance RK2 plasmid.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"448-467"},"PeriodicalIF":20.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01915-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020619","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 : 2025-01-22DOI: 10.1038/s41564-024-01922-4
Lauren C. Radlinski, Andreas J. Bäumler
Microbiome science is a multi-disciplinary field, but classical microbiologists are needed to ensure advances are grounded in our understanding of basic microbiological concepts.
{"title":"Microbiome science needs more microbiologists","authors":"Lauren C. Radlinski, Andreas J. Bäumler","doi":"10.1038/s41564-024-01922-4","DOIUrl":"10.1038/s41564-024-01922-4","url":null,"abstract":"Microbiome science is a multi-disciplinary field, but classical microbiologists are needed to ensure advances are grounded in our understanding of basic microbiological concepts.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"263-264"},"PeriodicalIF":20.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991908","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":"Author Correction: Adaptive loss of tRNA gene expression leads to phage resistance in a marine Synechococcus cyanobacterium","authors":"Sophia Zborowsky, Ran Tahan, Debbie Lindell","doi":"10.1038/s41564-025-01934-8","DOIUrl":"https://doi.org/10.1038/s41564-025-01934-8","url":null,"abstract":"<p>Correction to: <i>Nature Microbiology</i> https://doi.org/10.1038/s41564-024-01877-6, published online 3 January 2025.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"28 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989808","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}
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