Pub Date : 2025-01-03DOI: 10.1038/s41564-024-01886-5
Sanika Vaidya, Dibya Saha, Daniel K. H. Rode, Gabriel Torrens, Mads F. Hansen, Praveen K. Singh, Eric Jelli, Kazuki Nosho, Hannah Jeckel, Stephan Göttig, Felipe Cava, Knut Drescher
For any organism, survival is enhanced by the ability to sense and respond to threats in advance. For bacteria, danger sensing among kin cells has been observed, but the presence or impacts of general danger signals are poorly understood. Here we show that different bacterial species use exogenous peptidoglycan fragments, which are released by nearby kin or non-kin cell lysis, as a general danger signal. Using microscopy and gene expression profiling of Vibrio cholerae, we find that even brief signal exposure results in a regulatory response that causes three-dimensional biofilm formation, which protects cells from a broad range of stresses, including bacteriophage predation. A diverse set of species (Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis) also respond to exogenous peptidoglycan by forming biofilms. As peptidoglycan from different Gram-negative and Gram-positive species triggered three-dimensional biofilm formation, we propose that this danger signal and danger response are conserved among bacteria. Peptidoglycan released by neighbouring kin or non-kin cell lysis induces physiological changes that protect from a range of stresses, including phage predation.
{"title":"Bacteria use exogenous peptidoglycan as a danger signal to trigger biofilm formation","authors":"Sanika Vaidya, Dibya Saha, Daniel K. H. Rode, Gabriel Torrens, Mads F. Hansen, Praveen K. Singh, Eric Jelli, Kazuki Nosho, Hannah Jeckel, Stephan Göttig, Felipe Cava, Knut Drescher","doi":"10.1038/s41564-024-01886-5","DOIUrl":"10.1038/s41564-024-01886-5","url":null,"abstract":"For any organism, survival is enhanced by the ability to sense and respond to threats in advance. For bacteria, danger sensing among kin cells has been observed, but the presence or impacts of general danger signals are poorly understood. Here we show that different bacterial species use exogenous peptidoglycan fragments, which are released by nearby kin or non-kin cell lysis, as a general danger signal. Using microscopy and gene expression profiling of Vibrio cholerae, we find that even brief signal exposure results in a regulatory response that causes three-dimensional biofilm formation, which protects cells from a broad range of stresses, including bacteriophage predation. A diverse set of species (Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis) also respond to exogenous peptidoglycan by forming biofilms. As peptidoglycan from different Gram-negative and Gram-positive species triggered three-dimensional biofilm formation, we propose that this danger signal and danger response are conserved among bacteria. Peptidoglycan released by neighbouring kin or non-kin cell lysis induces physiological changes that protect from a range of stresses, including phage predation.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 1","pages":"144-157"},"PeriodicalIF":20.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01886-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917087","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 : 2025-01-03DOI: 10.1038/s41564-024-01877-6
Sophia Zborowsky, Ran Tahan, Debbie Lindell
Synechococcus is a significant primary producer in the oceans, coexisting with cyanophages, which are important agents of mortality. Bacterial resistance against phage infection is a topic of significant interest, yet little is known for ecologically relevant systems. Here we use exogenous gene expression and gene disruption to investigate mechanisms underlying intracellular resistance of marine Synechococcus WH5701 to the Syn9 cyanophage. The restriction–modification and Gabija defence systems possessed by Synechococcus WH5701 did not contribute to resistance. Instead, resistance was primarily driven by insufficient levels of LeuTAA tRNA, preventing translation of key phage genes in a passive, intracellular mode of resistance. Restoring cellular tRNA expression rendered the cyanobacterium sensitive to infection. We propose an evolutionary scenario whereby changes in cell codon usage, acquisition of tRNAs by the phage and loss of cell and phage tRNA expression resulted in an effective means of resistance, highlighting the dynamic interplay between bacteria and phages in shaping their co-evolutionary trajectories. Depletion of host LeuTAA tRNA levels prevents the translation of key cyanophage genes during infection and represents a passive, intracellular mode of resistance with implications for co-evolution.
{"title":"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/s41564-024-01877-6","DOIUrl":"10.1038/s41564-024-01877-6","url":null,"abstract":"Synechococcus is a significant primary producer in the oceans, coexisting with cyanophages, which are important agents of mortality. Bacterial resistance against phage infection is a topic of significant interest, yet little is known for ecologically relevant systems. Here we use exogenous gene expression and gene disruption to investigate mechanisms underlying intracellular resistance of marine Synechococcus WH5701 to the Syn9 cyanophage. The restriction–modification and Gabija defence systems possessed by Synechococcus WH5701 did not contribute to resistance. Instead, resistance was primarily driven by insufficient levels of LeuTAA tRNA, preventing translation of key phage genes in a passive, intracellular mode of resistance. Restoring cellular tRNA expression rendered the cyanobacterium sensitive to infection. We propose an evolutionary scenario whereby changes in cell codon usage, acquisition of tRNAs by the phage and loss of cell and phage tRNA expression resulted in an effective means of resistance, highlighting the dynamic interplay between bacteria and phages in shaping their co-evolutionary trajectories. Depletion of host LeuTAA tRNA levels prevents the translation of key cyanophage genes during infection and represents a passive, intracellular mode of resistance with implications for co-evolution.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 1","pages":"66-76"},"PeriodicalIF":20.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01877-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917088","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 : 2025-01-03DOI: 10.1038/s41564-024-01888-3
Robin R. Rohwer, Mark Kirkpatrick, Sarahi L. Garcia, Matthew Kellom, Katherine D. McMahon, Brett J. Baker
Ecology and evolution are considered distinct processes that interact on contemporary time scales in microbiomes. Here, to observe these processes in a natural system, we collected a two-decade, 471-metagenome time series from Lake Mendota (Wisconsin, USA). We assembled 2,855 species-representative genomes and found that genomic change was common and frequent. By tracking strain composition via single nucleotide variants, we identified cyclical seasonal patterns in 80% and decadal shifts in 20% of species. In the dominant freshwater family Nanopelagicaceae, environmental extremes coincided with shifts in strain composition and positive selection of amino acid and nucleic acid metabolism genes. These genes identify organic nitrogen compounds as potential drivers of freshwater responses to global change. Seasonal and long-term strain dynamics could be regarded as ecological processes or, equivalently, as evolutionary change. Rather than as distinct interacting processes, we propose a conceptualization of ecology and evolution as a continuum to better describe change in microbial communities. A 471-metagenome time series from Lake Mendota in Wisconsin, USA, reveals seasonal and decadal shifts in bacterial functional and ecological dynamics, especially in response to environmental extremes.
{"title":"Two decades of bacterial ecology and evolution in a freshwater lake","authors":"Robin R. Rohwer, Mark Kirkpatrick, Sarahi L. Garcia, Matthew Kellom, Katherine D. McMahon, Brett J. Baker","doi":"10.1038/s41564-024-01888-3","DOIUrl":"10.1038/s41564-024-01888-3","url":null,"abstract":"Ecology and evolution are considered distinct processes that interact on contemporary time scales in microbiomes. Here, to observe these processes in a natural system, we collected a two-decade, 471-metagenome time series from Lake Mendota (Wisconsin, USA). We assembled 2,855 species-representative genomes and found that genomic change was common and frequent. By tracking strain composition via single nucleotide variants, we identified cyclical seasonal patterns in 80% and decadal shifts in 20% of species. In the dominant freshwater family Nanopelagicaceae, environmental extremes coincided with shifts in strain composition and positive selection of amino acid and nucleic acid metabolism genes. These genes identify organic nitrogen compounds as potential drivers of freshwater responses to global change. Seasonal and long-term strain dynamics could be regarded as ecological processes or, equivalently, as evolutionary change. Rather than as distinct interacting processes, we propose a conceptualization of ecology and evolution as a continuum to better describe change in microbial communities. A 471-metagenome time series from Lake Mendota in Wisconsin, USA, reveals seasonal and decadal shifts in bacterial functional and ecological dynamics, especially in response to environmental extremes.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 1","pages":"246-257"},"PeriodicalIF":20.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917051","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 : 2025-01-03DOI: 10.1038/s41564-024-01878-5
Wilhelm Furnon, Vanessa M. Cowton, Giuditta De Lorenzo, Richard Orton, Vanessa Herder, Diego Cantoni, Georgios Ilia, Diogo Correa Mendonca, Karen Kerr, Jay Allan, Nicole Upfold, Gavin R. Meehan, Siddharth Bakshi, Udeet Ranjan Das, Sergi Molina Arias, Marion McElwee, Sarah Little, Nicola Logan, Kirsty Kwok, Katherine Smollett, Brian J. Willett, Ana Da Silva Filipe, David L. Robertson, Joe Grove, Arvind H. Patel, Massimo Palmarini
SARS-CoV-2 variants are mainly defined by mutations in their spike. It is therefore critical to understand how the evolutionary trajectories of spike affect virus phenotypes. So far, it has been challenging to comprehensively compare the many spikes that emerged during the pandemic in a single experimental platform. Here we generated a panel of recombinant viruses carrying different spike proteins from 27 variants circulating between 2020 and 2024 in the same genomic background. We then assessed several of their phenotypic traits both in vitro and in vivo. We found distinct phenotypic trajectories of spike among and between variants circulating before and after the emergence of Omicron variants. Spike of post-Omicron variants maintained enhanced tropism for the nasal epithelium and large airways but displayed, over time, several phenotypic traits typical of the pre-Omicron variants. Hence, spike with phenotypic features of both pre- and post-Omicron variants may continue to emerge in the future. Systematic comparison of SARS-CoV-2 spike proteins from pre- and post-Omicron variants in cell lines, primary respiratory epithelial cells and Syrian hamsters show distinct phenotypic trajectories in replication kinetics, cell tropism, cell-to-cell fusion, spike processing, cell entry routes and virulence.
{"title":"Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic","authors":"Wilhelm Furnon, Vanessa M. Cowton, Giuditta De Lorenzo, Richard Orton, Vanessa Herder, Diego Cantoni, Georgios Ilia, Diogo Correa Mendonca, Karen Kerr, Jay Allan, Nicole Upfold, Gavin R. Meehan, Siddharth Bakshi, Udeet Ranjan Das, Sergi Molina Arias, Marion McElwee, Sarah Little, Nicola Logan, Kirsty Kwok, Katherine Smollett, Brian J. Willett, Ana Da Silva Filipe, David L. Robertson, Joe Grove, Arvind H. Patel, Massimo Palmarini","doi":"10.1038/s41564-024-01878-5","DOIUrl":"10.1038/s41564-024-01878-5","url":null,"abstract":"SARS-CoV-2 variants are mainly defined by mutations in their spike. It is therefore critical to understand how the evolutionary trajectories of spike affect virus phenotypes. So far, it has been challenging to comprehensively compare the many spikes that emerged during the pandemic in a single experimental platform. Here we generated a panel of recombinant viruses carrying different spike proteins from 27 variants circulating between 2020 and 2024 in the same genomic background. We then assessed several of their phenotypic traits both in vitro and in vivo. We found distinct phenotypic trajectories of spike among and between variants circulating before and after the emergence of Omicron variants. Spike of post-Omicron variants maintained enhanced tropism for the nasal epithelium and large airways but displayed, over time, several phenotypic traits typical of the pre-Omicron variants. Hence, spike with phenotypic features of both pre- and post-Omicron variants may continue to emerge in the future. Systematic comparison of SARS-CoV-2 spike proteins from pre- and post-Omicron variants in cell lines, primary respiratory epithelial cells and Syrian hamsters show distinct phenotypic trajectories in replication kinetics, cell tropism, cell-to-cell fusion, spike processing, cell entry routes and virulence.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 1","pages":"77-93"},"PeriodicalIF":20.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01878-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917050","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 : 2025-01-02DOI: 10.1038/s41564-024-01890-9
Xueliang Wang, Yi Fang, Wei Liang, Yuhong Cai, Chi Chun Wong, Junlin Wang, Na Wang, Harry Cheuk-Hay Lau, Ying Jiao, Xingyu Zhou, Liufang Ye, Mengmiao Mo, Tao Yang, Miao Fan, Lei Song, Heming Zhou, Qiang Zhao, Eagle Siu-Hong Chu, Meinong Liang, Weixin Liu, Xin Liu, Shuaiyin Zhang, Haitao Shang, Hong Wei, Xiaoxing Li, Lixia Xu, Bing Liao, Joseph J. Y. Sung, Ming Kuang, Jun Yu
Hepatocellular carcinoma (HCC) is accompanied by an altered gut microbiota but whether the latter contributes to carcinogenesis is unclear. Here we show that faecal microbiota transplantation (FMT) using stool samples from patients with HCC spontaneously initiate liver inflammation, fibrosis and dysplasia in wild-type mice, and accelerate disease progression in a mouse model of HCC. We find that HCC-FMT results in gut barrier injury and translocation of live bacteria to the liver. Metagenomic analyses and bacterial culture of liver tissues reveal enrichment of the gut pathogen Klebsiella pneumoniae in patients with HCC and mice transplanted with the HCC microbiota. Moreover, K. pneumoniae monocolonization recapitulates the effect of HCC-FMT in promoting liver inflammation and hepatocarcinogenesis. Mechanistically, K. pneumoniae surface protein PBP1B interacts with and activates TLR4 on HCC cells, leading to increased cell proliferation and activation of oncogenic signalling. Targeting gut colonization using K. oxytoca or TLR4 inhibition represses K. pneumoniae-induced HCC progression. These findings indicate a role for an altered gut microbiota in hepatocarcinogenesis. Transfer of faecal microbiota from hepatocellular carcinoma patients to mice promotes carcinogenesis via live gut pathogenic Klebsiella pneumoniae translocating to the liver.
{"title":"Gut–liver translocation of pathogen Klebsiella pneumoniae promotes hepatocellular carcinoma in mice","authors":"Xueliang Wang, Yi Fang, Wei Liang, Yuhong Cai, Chi Chun Wong, Junlin Wang, Na Wang, Harry Cheuk-Hay Lau, Ying Jiao, Xingyu Zhou, Liufang Ye, Mengmiao Mo, Tao Yang, Miao Fan, Lei Song, Heming Zhou, Qiang Zhao, Eagle Siu-Hong Chu, Meinong Liang, Weixin Liu, Xin Liu, Shuaiyin Zhang, Haitao Shang, Hong Wei, Xiaoxing Li, Lixia Xu, Bing Liao, Joseph J. Y. Sung, Ming Kuang, Jun Yu","doi":"10.1038/s41564-024-01890-9","DOIUrl":"10.1038/s41564-024-01890-9","url":null,"abstract":"Hepatocellular carcinoma (HCC) is accompanied by an altered gut microbiota but whether the latter contributes to carcinogenesis is unclear. Here we show that faecal microbiota transplantation (FMT) using stool samples from patients with HCC spontaneously initiate liver inflammation, fibrosis and dysplasia in wild-type mice, and accelerate disease progression in a mouse model of HCC. We find that HCC-FMT results in gut barrier injury and translocation of live bacteria to the liver. Metagenomic analyses and bacterial culture of liver tissues reveal enrichment of the gut pathogen Klebsiella pneumoniae in patients with HCC and mice transplanted with the HCC microbiota. Moreover, K. pneumoniae monocolonization recapitulates the effect of HCC-FMT in promoting liver inflammation and hepatocarcinogenesis. Mechanistically, K. pneumoniae surface protein PBP1B interacts with and activates TLR4 on HCC cells, leading to increased cell proliferation and activation of oncogenic signalling. Targeting gut colonization using K. oxytoca or TLR4 inhibition represses K. pneumoniae-induced HCC progression. These findings indicate a role for an altered gut microbiota in hepatocarcinogenesis. Transfer of faecal microbiota from hepatocellular carcinoma patients to mice promotes carcinogenesis via live gut pathogenic Klebsiella pneumoniae translocating to the liver.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 1","pages":"169-184"},"PeriodicalIF":20.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01890-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911428","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 : 2025-01-02DOI: 10.1038/s41564-024-01883-8
Megan M. Tu, Lindsey A. Carfrae, Kenneth Rachwalski, Shawn French, Denise Catacutan, Rodion Gordzevich, Craig R. MacNair, Melissa E. Speagle, Firas Werah, Jonathan M. Stokes, Eric D. Brown
Carbapenems are last-resort antibiotics for treating bacterial infections. The widespread acquisition of metallo-β-lactamases, such as VIM-2, contributes to the emergence of carbapenem-resistant pathogens, and currently, no metallo-β-lactamase inhibitors are available in the clinic. Here we show that bacteria expressing VIM-2 have impaired growth in zinc-deprived environments, including human serum and murine infection models. Using transcriptomic, genomic and chemical probes, we identified molecular pathways critical for VIM-2 expression under zinc limitation. In particular, disruption of envelope stress response pathways reduced the growth of VIM-2-expressing bacteria in vitro and in vivo. Furthermore, we showed that VIM-2 expression disrupts the integrity of the outer membrane, rendering VIM-2-expressing bacteria more susceptible to azithromycin. Using a systemic murine infection model, we showed azithromycin’s therapeutic potential against VIM-2-expressing pathogens. In all, our findings provide a framework to exploit the fitness trade-offs of resistance, potentially accelerating the discovery of additional treatments for infections caused by multidrug-resistant bacteria. Expression of VIM-2 leads to physiological trade-offs for bacterial pathogens that can be exploited to treat infections caused by multidrug-resistant bacteria.
{"title":"Exploiting the fitness cost of metallo-β-lactamase expression can overcome antibiotic resistance in bacterial pathogens","authors":"Megan M. Tu, Lindsey A. Carfrae, Kenneth Rachwalski, Shawn French, Denise Catacutan, Rodion Gordzevich, Craig R. MacNair, Melissa E. Speagle, Firas Werah, Jonathan M. Stokes, Eric D. Brown","doi":"10.1038/s41564-024-01883-8","DOIUrl":"10.1038/s41564-024-01883-8","url":null,"abstract":"Carbapenems are last-resort antibiotics for treating bacterial infections. The widespread acquisition of metallo-β-lactamases, such as VIM-2, contributes to the emergence of carbapenem-resistant pathogens, and currently, no metallo-β-lactamase inhibitors are available in the clinic. Here we show that bacteria expressing VIM-2 have impaired growth in zinc-deprived environments, including human serum and murine infection models. Using transcriptomic, genomic and chemical probes, we identified molecular pathways critical for VIM-2 expression under zinc limitation. In particular, disruption of envelope stress response pathways reduced the growth of VIM-2-expressing bacteria in vitro and in vivo. Furthermore, we showed that VIM-2 expression disrupts the integrity of the outer membrane, rendering VIM-2-expressing bacteria more susceptible to azithromycin. Using a systemic murine infection model, we showed azithromycin’s therapeutic potential against VIM-2-expressing pathogens. In all, our findings provide a framework to exploit the fitness trade-offs of resistance, potentially accelerating the discovery of additional treatments for infections caused by multidrug-resistant bacteria. Expression of VIM-2 leads to physiological trade-offs for bacterial pathogens that can be exploited to treat infections caused by multidrug-resistant bacteria.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 1","pages":"53-65"},"PeriodicalIF":20.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911426","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 : 2025-01-02DOI: 10.1038/s41564-024-01881-w
Tiffany Y. Hsu, Etienne Nzabarushimana, Dennis Wong, Chengwei Luo, Robert G. Beiko, Morgan Langille, Curtis Huttenhower, Long H. Nguyen, Eric A. Franzosa
Lateral gene transfer (LGT), also known as horizontal gene transfer, facilitates genomic diversification in microbial populations. While previous work has surveyed LGT in human-associated microbial isolate genomes, the landscape of LGT arising in personal microbiomes is not well understood, as there are no widely adopted methods to characterize LGT from complex communities. Here we developed, benchmarked and validated a computational algorithm (WAAFLE or Workflow to Annotate Assemblies and Find LGT Events) to profile LGT from assembled metagenomes. WAAFLE prioritizes specificity while maintaining high sensitivity for intergenus LGT. Applying WAAFLE to >2,000 human metagenomes from diverse body sites, we identified >100,000 high-confidence previously uncharacterized LGT (~2 per microbial genome-equivalent). These were enriched for mobile elements, as well as restriction–modification functions associated with the destruction of foreign DNA. LGT frequency was influenced by biogeography, phylogenetic similarity of involved pairs (for example, Fusobacterium periodonticum and F. nucleatum) and donor abundance. These forces manifest as networks in which hub taxa donate unequally with phylogenetic neighbours. Our findings suggest that human microbiome LGT may be more ubiquitous than previously described. Applying WAAFLE to metagenomic data from human samples reveals over 100,000 putative LGTs not currently found in reference genomes, highlighting an underappreciated microbiome phenomenon.
{"title":"Profiling lateral gene transfer events in the human microbiome using WAAFLE","authors":"Tiffany Y. Hsu, Etienne Nzabarushimana, Dennis Wong, Chengwei Luo, Robert G. Beiko, Morgan Langille, Curtis Huttenhower, Long H. Nguyen, Eric A. Franzosa","doi":"10.1038/s41564-024-01881-w","DOIUrl":"10.1038/s41564-024-01881-w","url":null,"abstract":"Lateral gene transfer (LGT), also known as horizontal gene transfer, facilitates genomic diversification in microbial populations. While previous work has surveyed LGT in human-associated microbial isolate genomes, the landscape of LGT arising in personal microbiomes is not well understood, as there are no widely adopted methods to characterize LGT from complex communities. Here we developed, benchmarked and validated a computational algorithm (WAAFLE or Workflow to Annotate Assemblies and Find LGT Events) to profile LGT from assembled metagenomes. WAAFLE prioritizes specificity while maintaining high sensitivity for intergenus LGT. Applying WAAFLE to >2,000 human metagenomes from diverse body sites, we identified >100,000 high-confidence previously uncharacterized LGT (~2 per microbial genome-equivalent). These were enriched for mobile elements, as well as restriction–modification functions associated with the destruction of foreign DNA. LGT frequency was influenced by biogeography, phylogenetic similarity of involved pairs (for example, Fusobacterium periodonticum and F. nucleatum) and donor abundance. These forces manifest as networks in which hub taxa donate unequally with phylogenetic neighbours. Our findings suggest that human microbiome LGT may be more ubiquitous than previously described. Applying WAAFLE to metagenomic data from human samples reveals over 100,000 putative LGTs not currently found in reference genomes, highlighting an underappreciated microbiome phenomenon.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 1","pages":"94-111"},"PeriodicalIF":20.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911429","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 : 2025-01-02DOI: 10.1038/s41564-024-01874-9
Grégoire Michoud, Hannes Peter, Susheel Bhanu Busi, Massimo Bourquin, Tyler J. Kohler, Aileen Geers, Leila Ezzat, The Vanishing Glaciers Field Team, Tom J. Battin
Glacier-fed streams (GFS) feature among Earth’s most extreme aquatic ecosystems marked by pronounced oligotrophy and environmental fluctuations. Microorganisms mainly organize in biofilms within them, but how they cope with such conditions is unknown. Here, leveraging 156 metagenomes from the Vanishing Glaciers project obtained from sediment samples in GFS from 9 mountains ranges, we report thousands of metagenome-assembled genomes (MAGs) encompassing prokaryotes, algae, fungi and viruses, that shed light on biotic interactions within glacier-fed stream biofilms. A total of 2,855 bacterial MAGs were characterized by diverse strategies to exploit inorganic and organic energy sources, in part via functional redundancy and mixotrophy. We show that biofilms probably become more complex and switch from chemoautotrophy to heterotrophy as algal biomass increases in GFS owing to glacier shrinkage. Our MAG compendium sheds light on the success of microbial life in GFS and provides a resource for future research on a microbiome potentially impacted by climate change. Thousands of metagenome-assembled genomes from the Vanishing Glaciers project showcase the interactions between prokaryotes, algae, fungi and viruses in glacier-fed stream environments.
{"title":"Mapping the metagenomic diversity of the multi-kingdom glacier-fed stream microbiome","authors":"Grégoire Michoud, Hannes Peter, Susheel Bhanu Busi, Massimo Bourquin, Tyler J. Kohler, Aileen Geers, Leila Ezzat, The Vanishing Glaciers Field Team, Tom J. Battin","doi":"10.1038/s41564-024-01874-9","DOIUrl":"10.1038/s41564-024-01874-9","url":null,"abstract":"Glacier-fed streams (GFS) feature among Earth’s most extreme aquatic ecosystems marked by pronounced oligotrophy and environmental fluctuations. Microorganisms mainly organize in biofilms within them, but how they cope with such conditions is unknown. Here, leveraging 156 metagenomes from the Vanishing Glaciers project obtained from sediment samples in GFS from 9 mountains ranges, we report thousands of metagenome-assembled genomes (MAGs) encompassing prokaryotes, algae, fungi and viruses, that shed light on biotic interactions within glacier-fed stream biofilms. A total of 2,855 bacterial MAGs were characterized by diverse strategies to exploit inorganic and organic energy sources, in part via functional redundancy and mixotrophy. We show that biofilms probably become more complex and switch from chemoautotrophy to heterotrophy as algal biomass increases in GFS owing to glacier shrinkage. Our MAG compendium sheds light on the success of microbial life in GFS and provides a resource for future research on a microbiome potentially impacted by climate change. Thousands of metagenome-assembled genomes from the Vanishing Glaciers project showcase the interactions between prokaryotes, algae, fungi and viruses in glacier-fed stream environments.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 1","pages":"217-230"},"PeriodicalIF":20.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911430","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 : 2025-01-02DOI: 10.1038/s41564-024-01889-2
Hugo Vaysset, Chance Meers, Jean Cury, Aude Bernheim, Samuel H. Sternberg
Transposase genes are ubiquitous in all domains of life and provide a rich reservoir for the evolution of novel protein functions. Here we report deep evolutionary links between bacterial IS110-family transposases, which catalyse RNA-guided DNA recombination using bridge RNAs, and archaeal/eukaryotic Nop5-family proteins, which promote RNA-guided RNA 2′-O-methylation using C/D-box snoRNAs. On the basis of conservation of protein sequence, domain architecture, three-dimensional structure and non-coding RNA features, alongside phylogenetic analyses, we propose that programmable RNA modification emerged through the exaptation of components derived from IS110-like transposons. These findings underscore how recurrent domestication events of transposable elements have driven the evolution of RNA-guided mechanisms. Structural and phylogenetic analyses show that programmable RNA modifications ubiquitous in archaea and eukarya arose from bacterial transposons.
转座酶基因普遍存在于生命的各个领域，并为新蛋白质功能的进化提供了丰富的储备。在这里，我们报告了细菌is110家族转座酶和古细菌/真核生物nop5家族蛋白之间的深层进化联系，前者通过桥接RNA催化RNA引导的DNA重组，后者通过C/D-box snoRNAs促进RNA引导的RNA 2 ' - o -甲基化。基于蛋白质序列的保守性、结构域结构、三维结构和非编码RNA的特征，以及系统发育分析，我们提出可编程RNA修饰是通过提取来自is110样转座子的成分而出现的。这些发现强调了转座因子的反复驯化事件如何推动rna引导机制的进化。
{"title":"Evolutionary origins of archaeal and eukaryotic RNA-guided RNA modification in bacterial IS110 transposons","authors":"Hugo Vaysset, Chance Meers, Jean Cury, Aude Bernheim, Samuel H. Sternberg","doi":"10.1038/s41564-024-01889-2","DOIUrl":"10.1038/s41564-024-01889-2","url":null,"abstract":"Transposase genes are ubiquitous in all domains of life and provide a rich reservoir for the evolution of novel protein functions. Here we report deep evolutionary links between bacterial IS110-family transposases, which catalyse RNA-guided DNA recombination using bridge RNAs, and archaeal/eukaryotic Nop5-family proteins, which promote RNA-guided RNA 2′-O-methylation using C/D-box snoRNAs. On the basis of conservation of protein sequence, domain architecture, three-dimensional structure and non-coding RNA features, alongside phylogenetic analyses, we propose that programmable RNA modification emerged through the exaptation of components derived from IS110-like transposons. These findings underscore how recurrent domestication events of transposable elements have driven the evolution of RNA-guided mechanisms. Structural and phylogenetic analyses show that programmable RNA modifications ubiquitous in archaea and eukarya arose from bacterial transposons.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 1","pages":"20-27"},"PeriodicalIF":20.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911431","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 : 2025-01-02DOI: 10.1038/s41564-024-01887-4
Matthew R. Olm, Sean P. Spencer, Tadashi Takeuchi, Evelyn Lemus Silva, Justin L. Sonnenburg
IgA, the primary human antibody secreted from the gut mucosa, shapes the intestinal microbiota. Methodological limitations have hindered defining which microbial strains are targeted by IgA and the implications of binding. Here we develop a technique, metagenomic immunoglobulin sequencing (MIg-seq), that provides strain-level resolution of microbes coated by IgA and use it to determine IgA coating levels for 3,520 gut microbiome strains in healthy human faeces. We find that both health and disease-associated bacteria are targeted by IgA. Microbial genes are highly predictive of IgA binding levels; in particular, mucus degradation genes are correlated with high binding, and replication rates are significantly reduced for microbes bound by IgA. We demonstrate that IgA binding is more correlated with host immune status than traditional relative abundance measures of microbial community composition. This study introduces a powerful technique for assessing strain-level IgA binding in human stool, paving the way for deeper understanding of IgA-based host–microbe interactions. Metagenomic immunoglobulin sequencing (MIg-seq) uncovered patterns of IgA antibody binding of bacterial strains in the healthy human gut microbiome.
{"title":"Metagenomic immunoglobulin sequencing reveals IgA coating of microbial strains in the healthy human gut","authors":"Matthew R. Olm, Sean P. Spencer, Tadashi Takeuchi, Evelyn Lemus Silva, Justin L. Sonnenburg","doi":"10.1038/s41564-024-01887-4","DOIUrl":"10.1038/s41564-024-01887-4","url":null,"abstract":"IgA, the primary human antibody secreted from the gut mucosa, shapes the intestinal microbiota. Methodological limitations have hindered defining which microbial strains are targeted by IgA and the implications of binding. Here we develop a technique, metagenomic immunoglobulin sequencing (MIg-seq), that provides strain-level resolution of microbes coated by IgA and use it to determine IgA coating levels for 3,520 gut microbiome strains in healthy human faeces. We find that both health and disease-associated bacteria are targeted by IgA. Microbial genes are highly predictive of IgA binding levels; in particular, mucus degradation genes are correlated with high binding, and replication rates are significantly reduced for microbes bound by IgA. We demonstrate that IgA binding is more correlated with host immune status than traditional relative abundance measures of microbial community composition. This study introduces a powerful technique for assessing strain-level IgA binding in human stool, paving the way for deeper understanding of IgA-based host–microbe interactions. Metagenomic immunoglobulin sequencing (MIg-seq) uncovered patterns of IgA antibody binding of bacterial strains in the healthy human gut microbiome.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 1","pages":"112-125"},"PeriodicalIF":20.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911425","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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