Pub Date : 2024-07-23Epub Date: 2024-06-21DOI: 10.1128/msystems.00576-24
Aileen Berasategui, Hassan Salem, Abraham G Moller, Yuliana Christopher, Quimi Vidaurre Montoya, Caitlin Conn, Timothy D Read, Andre Rodrigues, Nadine Ziemert, Nicole Gerardo
The metabolic intimacy of symbiosis often demands the work of specialists. Natural products and defensive secondary metabolites can drive specificity by ensuring infection and propagation across host generations. But in contrast to bacteria, little is known about the diversity and distribution of natural product biosynthetic pathways among fungi and how they evolve to facilitate symbiosis and adaptation to their host environment. In this study, we define the secondary metabolism of Escovopsis and closely related genera, symbionts in the gardens of fungus-farming ants. We ask how the gain and loss of various biosynthetic pathways correspond to divergent lifestyles. Long-read sequencing allowed us to define the chromosomal features of representative Escovopsis strains, revealing highly reduced genomes composed of seven to eight chromosomes. The genomes are highly syntenic with macrosynteny decreasing with increasing phylogenetic distance, while maintaining a high degree of mesosynteny. An ancestral state reconstruction analysis of biosynthetic pathways revealed that, while many secondary metabolites are shared with non-ant-associated Sordariomycetes, 56 pathways are unique to the symbiotic genera. Reflecting adaptation to diverging ant agricultural systems, we observe that the stepwise acquisition of these pathways mirrors the ecological radiations of attine ants and the dynamic recruitment and replacement of their fungal cultivars. As different clades encode characteristic combinations of biosynthetic gene clusters, these delineating profiles provide important insights into the possible mechanisms underlying specificity between these symbionts and their fungal hosts. Collectively, our findings shed light on the evolutionary dynamic nature of secondary metabolism in Escovopsis and its allies, reflecting adaptation of the symbionts to an ancient agricultural system.IMPORTANCEMicrobial symbionts interact with their hosts and competitors through a remarkable array of secondary metabolites and natural products. Here, we highlight the highly streamlined genomic features of attine-associated fungal symbionts. The genomes of Escovopsis species, as well as species from other symbiont genera, many of which are common with the gardens of fungus-growing ants, are defined by seven chromosomes. Despite a high degree of metabolic conservation, we observe some variation in the symbionts' potential to produce secondary metabolites. As the phylogenetic distribution of the encoding biosynthetic gene clusters coincides with attine transitions in agricultural systems, we highlight the likely role of these metabolites in mediating adaptation by a group of highly specialized symbionts.
{"title":"Genomic insights into the evolution of secondary metabolism of <i>Escovopsis</i> and its allies, specialized fungal symbionts of fungus-farming ants.","authors":"Aileen Berasategui, Hassan Salem, Abraham G Moller, Yuliana Christopher, Quimi Vidaurre Montoya, Caitlin Conn, Timothy D Read, Andre Rodrigues, Nadine Ziemert, Nicole Gerardo","doi":"10.1128/msystems.00576-24","DOIUrl":"10.1128/msystems.00576-24","url":null,"abstract":"<p><p>The metabolic intimacy of symbiosis often demands the work of specialists. Natural products and defensive secondary metabolites can drive specificity by ensuring infection and propagation across host generations. But in contrast to bacteria, little is known about the diversity and distribution of natural product biosynthetic pathways among fungi and how they evolve to facilitate symbiosis and adaptation to their host environment. In this study, we define the secondary metabolism of <i>Escovopsis</i> and closely related genera, symbionts in the gardens of fungus-farming ants. We ask how the gain and loss of various biosynthetic pathways correspond to divergent lifestyles. Long-read sequencing allowed us to define the chromosomal features of representative <i>Escovopsis</i> strains, revealing highly reduced genomes composed of seven to eight chromosomes. The genomes are highly syntenic with macrosynteny decreasing with increasing phylogenetic distance, while maintaining a high degree of mesosynteny. An ancestral state reconstruction analysis of biosynthetic pathways revealed that, while many secondary metabolites are shared with non-ant-associated <i>Sordariomycetes</i>, 56 pathways are unique to the symbiotic genera. Reflecting adaptation to diverging ant agricultural systems, we observe that the stepwise acquisition of these pathways mirrors the ecological radiations of attine ants and the dynamic recruitment and replacement of their fungal cultivars. As different clades encode characteristic combinations of biosynthetic gene clusters, these delineating profiles provide important insights into the possible mechanisms underlying specificity between these symbionts and their fungal hosts. Collectively, our findings shed light on the evolutionary dynamic nature of secondary metabolism in <i>Escovopsis</i> and its allies, reflecting adaptation of the symbionts to an ancient agricultural system.IMPORTANCEMicrobial symbionts interact with their hosts and competitors through a remarkable array of secondary metabolites and natural products. Here, we highlight the highly streamlined genomic features of attine-associated fungal symbionts. The genomes of <i>Escovopsis</i> species, as well as species from other symbiont genera, many of which are common with the gardens of fungus-growing ants, are defined by seven chromosomes. Despite a high degree of metabolic conservation, we observe some variation in the symbionts' potential to produce secondary metabolites. As the phylogenetic distribution of the encoding biosynthetic gene clusters coincides with attine transitions in agricultural systems, we highlight the likely role of these metabolites in mediating adaptation by a group of highly specialized symbionts.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-07-23Epub Date: 2024-06-24DOI: 10.1128/msystems.00515-24
Ceylan Tanes, Vincent Tu, Scott Daniel, Kyle Bittinger
The method of 16S rRNA marker gene sequencing has fueled microbiome research and continues to be relevant. A perceived weakness of the method is that taxonomic assignments are not possible to make at the rank of species. We show that by working to rule out bacterial or archaeal species membership, we can provide an answer that is more accurate and useful. The Unassigner software operates on 16S rRNA marker gene data and computes a rule-out probability for species membership using a beta-binomial distribution. We demonstrate that our approach is accurate based on full-genome comparisons. Our method is consistent with existing approaches and dramatically improves on them based on the percentage of reads it can associate with a species in a sample. The software is available at https://github.com/PennChopMicrobiomeProgram/unassigner.IMPORTANCEWhile existing methods do not provide reliable species-level assignments for 16S rRNA marker gene data, the Unassigner software solves this problem by ruling out species membership, allowing researchers to reason at the species level.
{"title":"Unassigning bacterial species for microbiome studies.","authors":"Ceylan Tanes, Vincent Tu, Scott Daniel, Kyle Bittinger","doi":"10.1128/msystems.00515-24","DOIUrl":"10.1128/msystems.00515-24","url":null,"abstract":"<p><p>The method of 16S rRNA marker gene sequencing has fueled microbiome research and continues to be relevant. A perceived weakness of the method is that taxonomic assignments are not possible to make at the rank of species. We show that by working to <i>rule out</i> bacterial or archaeal species membership, we can provide an answer that is more accurate and useful. The Unassigner software operates on 16S rRNA marker gene data and computes a rule-out probability for species membership using a beta-binomial distribution. We demonstrate that our approach is accurate based on full-genome comparisons. Our method is consistent with existing approaches and dramatically improves on them based on the percentage of reads it can associate with a species in a sample. The software is available at https://github.com/PennChopMicrobiomeProgram/unassigner.IMPORTANCEWhile existing methods do not provide reliable species-level assignments for 16S rRNA marker gene data, the Unassigner software solves this problem by ruling out species membership, allowing researchers to reason at the species level.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-07-23Epub Date: 2024-06-27DOI: 10.1128/msystems.00127-24
Xin Yang, Yuesong Xu, Jie Li, Ximing Ran, Zhihao Gu, Linfeng Song, Lei Zhang, Li Wen, Guang Ji, Ruirui Wang
Cholestasis is a common morbid state that may occur in different phases; however, a comprehensive evaluation of the long-term effect post-recovery is still lacking. In the hepatic cholestasis mouse model, which was induced by a temporary complete blockage of the bile duct, the stasis of bile acids and liver damage typically recovered within a short period. However, we found that the temporary hepatic cholestasis had a long-term effect on gut microbiota dysbiosis, including overgrowth of small intestinal bacteria, decreased diversity of the gut microbiota, and an overall imbalance in its composition accompanied by an elevated inflammation level. Additionally, we observed an increase in Escherichia-Shigella (represented by ASV136078), rich in virulence factors, in both small and large intestines following cholestasis. To confirm the causal role of dysregulated gut microbiota in promoting hepatic inflammation and injury, we conducted gut microbiota transplantation into germ-free mice. We found that recipient mice transplanted with feces from cholestasis mice exhibited liver inflammation, damage, and accumulation of hepatic bile acids. In conclusion, our study demonstrates that cholestasis disrupts the overall load and structural composition of the gut microbiota in mice, and these adverse effects persist after recovery from cholestatic liver injury. This finding suggests the importance of monitoring the structural composition of the gut microbiota in patients with cholestasis and during their recovery.
Importance: Our pre-clinical study using a mouse model of cholestasis underscores that cholestasis not only disrupts the equilibrium and structural configuration of the gut microbiota but also emphasizes the persistence of these adverse effects even after bile stasis restoration. This suggests the need of monitoring and initiating interventions for gut microbiota structural restoration in patients with cholestasis during and after recovery. We believe that our study contributes to novel and better understanding of the intricate interplay among bile acid homeostasis, gut microbiota, and cholestasis-associated complications. Our pre-clinical findings may provide implications for the clinical management of patients with cholestasis.
{"title":"Bile acid-gut microbiota imbalance in cholestasis and its long-term effect in mice.","authors":"Xin Yang, Yuesong Xu, Jie Li, Ximing Ran, Zhihao Gu, Linfeng Song, Lei Zhang, Li Wen, Guang Ji, Ruirui Wang","doi":"10.1128/msystems.00127-24","DOIUrl":"10.1128/msystems.00127-24","url":null,"abstract":"<p><p>Cholestasis is a common morbid state that may occur in different phases; however, a comprehensive evaluation of the long-term effect post-recovery is still lacking. In the hepatic cholestasis mouse model, which was induced by a temporary complete blockage of the bile duct, the stasis of bile acids and liver damage typically recovered within a short period. However, we found that the temporary hepatic cholestasis had a long-term effect on gut microbiota dysbiosis, including overgrowth of small intestinal bacteria, decreased diversity of the gut microbiota, and an overall imbalance in its composition accompanied by an elevated inflammation level. Additionally, we observed an increase in <i>Escherichia-Shigella</i> (represented by ASV136078), rich in virulence factors, in both small and large intestines following cholestasis. To confirm the causal role of dysregulated gut microbiota in promoting hepatic inflammation and injury, we conducted gut microbiota transplantation into germ-free mice. We found that recipient mice transplanted with feces from cholestasis mice exhibited liver inflammation, damage, and accumulation of hepatic bile acids. In conclusion, our study demonstrates that cholestasis disrupts the overall load and structural composition of the gut microbiota in mice, and these adverse effects persist after recovery from cholestatic liver injury. This finding suggests the importance of monitoring the structural composition of the gut microbiota in patients with cholestasis and during their recovery.</p><p><strong>Importance: </strong>Our pre-clinical study using a mouse model of cholestasis underscores that cholestasis not only disrupts the equilibrium and structural configuration of the gut microbiota but also emphasizes the persistence of these adverse effects even after bile stasis restoration. This suggests the need of monitoring and initiating interventions for gut microbiota structural restoration in patients with cholestasis during and after recovery. We believe that our study contributes to novel and better understanding of the intricate interplay among bile acid homeostasis, gut microbiota, and cholestasis-associated complications. Our pre-clinical findings may provide implications for the clinical management of patients with cholestasis.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The analysis and comparison of genomes rely on different tools for tasks such as annotation, orthology prediction, and phylogenetic inference. Most tools are specialized for a single task, and additional efforts are necessary to integrate and visualize the results. To fill this gap, we developed zDB, an application integrating a Nextflow analysis pipeline and a Python visualization platform built on the Django framework. The application is available on GitHub (https://github.com/metagenlab/zDB) and from the bioconda channel. Starting from annotated Genbank files, zDB identifies orthologs and infers a phylogeny for each orthogroup. A species phylogeny is also constructed from shared single-copy orthologs. The results can be enriched with Pfam protein domain prediction, Cluster of Orthologs Genes and Kyoto Encyclopedia of Genes and Genomes annotations, and Swissprot homologs. The web application allows searching for specific genes or annotations, running Blast queries, and comparing genomic regions and whole genomes. The metabolic capacities of organisms can be compared at either the module or pathway levels. Finally, users can run queries to examine the conservation of specific genes or annotations across a chosen subset of genomes and display the results as a list of genes, Venn diagram, or heatmaps. Those features make zDB useful for both bioinformaticians and researchers more accustomed to laboratory research.IMPORTANCEGenome comparison and analysis rely on many independent tools, leaving to scientists the burden to integrate and visualize their results for interpretation. To alleviate this burden, we have built zDB, a comparative genomics tool that includes both an analysis pipeline and a visualization platform. The analysis pipeline automates gene annotation, orthology prediction, and phylogenetic inference, while the visualization platform allows scientists to easily explore the results in a web browser. Among other features, the interface allows users to visually compare whole genomes and targeted regions, assess the conservation of genes or metabolic pathways, perform Blast searches, or look for specific annotations. Altogether, this tool will be useful for a broad range of applications in comparative studies between two and hundred genomes. Furthermore, it is designed to allow sharing of data sets easily at a local or international scale, thereby supporting exploratory analyses for non-bioinformaticians on the genome of their favorite organisms.
{"title":"zDB: bacterial comparative genomics made easy.","authors":"Bastian Marquis, Trestan Pillonel, Alessia Carrara, Claire Bertelli","doi":"10.1128/msystems.00473-24","DOIUrl":"10.1128/msystems.00473-24","url":null,"abstract":"<p><p>The analysis and comparison of genomes rely on different tools for tasks such as annotation, orthology prediction, and phylogenetic inference. Most tools are specialized for a single task, and additional efforts are necessary to integrate and visualize the results. To fill this gap, we developed zDB, an application integrating a Nextflow analysis pipeline and a Python visualization platform built on the Django framework. The application is available on GitHub (https://github.com/metagenlab/zDB) and from the bioconda channel. Starting from annotated Genbank files, zDB identifies orthologs and infers a phylogeny for each orthogroup. A species phylogeny is also constructed from shared single-copy orthologs. The results can be enriched with Pfam protein domain prediction, Cluster of Orthologs Genes and Kyoto Encyclopedia of Genes and Genomes annotations, and Swissprot homologs. The web application allows searching for specific genes or annotations, running Blast queries, and comparing genomic regions and whole genomes. The metabolic capacities of organisms can be compared at either the module or pathway levels. Finally, users can run queries to examine the conservation of specific genes or annotations across a chosen subset of genomes and display the results as a list of genes, Venn diagram, or heatmaps. Those features make zDB useful for both bioinformaticians and researchers more accustomed to laboratory research.IMPORTANCEGenome comparison and analysis rely on many independent tools, leaving to scientists the burden to integrate and visualize their results for interpretation. To alleviate this burden, we have built zDB, a comparative genomics tool that includes both an analysis pipeline and a visualization platform. The analysis pipeline automates gene annotation, orthology prediction, and phylogenetic inference, while the visualization platform allows scientists to easily explore the results in a web browser. Among other features, the interface allows users to visually compare whole genomes and targeted regions, assess the conservation of genes or metabolic pathways, perform Blast searches, or look for specific annotations. Altogether, this tool will be useful for a broad range of applications in comparative studies between two and hundred genomes. Furthermore, it is designed to allow sharing of data sets easily at a local or international scale, thereby supporting exploratory analyses for non-bioinformaticians on the genome of their favorite organisms.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-07-23Epub Date: 2024-06-21DOI: 10.1128/msystems.00263-24
Maria Daniela Silva, Graça Pinto, Angela França, Joana Azeredo, Luís D R Melo
In nature, bacteria often survive in a stationary state with low metabolic activity. Phages use the metabolic machinery of the host cell to replicate, and, therefore, their efficacy against non-dividing cells is usually limited. Nevertheless, it was previously shown that the Staphylococcus epidermidis phage SEP1 has the remarkable capacity to actively replicate in stationary-phase cells, reducing their numbers. Here, we studied for the first time the transcriptomic profiles of both exponential and stationary cells infected with SEP1 phage using RNA-seq to gain a better understanding of this rare phenomenon. We showed that SEP1 successfully takes over the transcriptional apparatus of both exponential and stationary cells. Infection was, however, delayed in stationary cells, with genes within the gp142-gp154 module putatively implicated in host takeover. S. epidermidis responded to SEP1 infection by upregulating three genes involved in a DNA modification system, with this being observed already 5 min after infection in exponential cells and later in stationary cells. In stationary cells, a significant number of genes involved in translation and RNA metabolic and biosynthetic processes were upregulated after 15 and 30 min of SEP1 infection in comparison with the uninfected control, showing that SEP1 activates metabolic and biosynthetic pathways necessary to its successful replication.IMPORTANCEMost phage-host interaction studies are performed with exponentially growing cells. However, this cell state is not representative of what happens in natural environments. Additionally, most phages fail to replicate in stationary cells. The Staphylococcus epidermidis phage SEP1 is one of the few phages reported to date to be able to infect stationary cells. Here, we unveiled the interaction of SEP1 with its host in both exponential and stationary states of growth at the transcriptomic level. The findings of this study provide valuable insights for a better implementation of phage therapy since phages able to infect stationary cells could be more efficient in the treatment of recalcitrant infections.
{"title":"Phage SEP1 hijacks <i>Staphylococcus epidermidis</i> stationary cells' metabolism to replicate.","authors":"Maria Daniela Silva, Graça Pinto, Angela França, Joana Azeredo, Luís D R Melo","doi":"10.1128/msystems.00263-24","DOIUrl":"10.1128/msystems.00263-24","url":null,"abstract":"<p><p>In nature, bacteria often survive in a stationary state with low metabolic activity. Phages use the metabolic machinery of the host cell to replicate, and, therefore, their efficacy against non-dividing cells is usually limited. Nevertheless, it was previously shown that the <i>Staphylococcus epidermidis</i> phage SEP1 has the remarkable capacity to actively replicate in stationary-phase cells, reducing their numbers. Here, we studied for the first time the transcriptomic profiles of both exponential and stationary cells infected with SEP1 phage using RNA-seq to gain a better understanding of this rare phenomenon. We showed that SEP1 successfully takes over the transcriptional apparatus of both exponential and stationary cells. Infection was, however, delayed in stationary cells, with genes within the <i>gp142-gp154</i> module putatively implicated in host takeover. <i>S. epidermidis</i> responded to SEP1 infection by upregulating three genes involved in a DNA modification system, with this being observed already 5 min after infection in exponential cells and later in stationary cells. In stationary cells, a significant number of genes involved in translation and RNA metabolic and biosynthetic processes were upregulated after 15 and 30 min of SEP1 infection in comparison with the uninfected control, showing that SEP1 activates metabolic and biosynthetic pathways necessary to its successful replication.IMPORTANCEMost phage-host interaction studies are performed with exponentially growing cells. However, this cell state is not representative of what happens in natural environments. Additionally, most phages fail to replicate in stationary cells. The <i>Staphylococcus epidermidis</i> phage SEP1 is one of the few phages reported to date to be able to infect stationary cells. Here, we unveiled the interaction of SEP1 with its host in both exponential and stationary states of growth at the transcriptomic level. The findings of this study provide valuable insights for a better implementation of phage therapy since phages able to infect stationary cells could be more efficient in the treatment of recalcitrant infections.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-07-23Epub Date: 2024-06-10DOI: 10.1128/msystems.00709-23
Lauren E Krausfeldt, Elizaveta Shmakova, Hyo Won Lee, Viviana Mazzei, Keith A Loftin, Robert P Smith, Emily Karwacki, P Eric Fortman, Barry H Rosen, Hidetoshi Urakawa, Manoj Dadlani, Rita R Colwell, Jose V Lopez
The occurrence of cyanobacterial harmful algal blooms (cyanoHABs) is related to their physical and chemical environment. However, less is known about their associated microbial interactions and processes. In this study, cyanoHABs were analyzed as a microbial ecosystem, using 1 year of 16S rRNA sequencing and 70 metagenomes collected during the bloom season from Lake Okeechobee (Florida, USA). Biogeographical patterns observed in microbial community composition and function reflected ecological zones distinct in their physical and chemical parameters that resulted in bloom "hotspots" near major lake inflows. Changes in relative abundances of taxa within multiple phyla followed increasing bloom severity. Functional pathways that correlated with increasing bloom severity encoded organic nitrogen and phosphorus utilization, storage of nutrients, exchange of genetic material, phage defense, and protection against oxidative stress, suggesting that microbial interactions may promote cyanoHAB resilience. Cyanobacterial communities were highly diverse, with picocyanobacteria ubiquitous and oftentimes most abundant, especially in the absence of blooms. The identification of novel bloom-forming cyanobacteria and genomic comparisons indicated a functionally diverse cyanobacterial community with differences in its capability to store nitrogen using cyanophycin and to defend against phage using CRISPR and restriction-modification systems. Considering blooms in the context of a microbial ecosystem and their interactions in nature, physiologies and interactions supporting the proliferation and stability of cyanoHABs are proposed, including a role for phage infection of picocyanobacteria. This study displayed the power of "-omics" to reveal important biological processes that could support the effective management and prediction of cyanoHABs.
Importance: Cyanobacterial harmful algal blooms pose a significant threat to aquatic ecosystems and human health. Although physical and chemical conditions in aquatic systems that facilitate bloom development are well studied, there are fundamental gaps in the biological understanding of the microbial ecosystem that makes a cyanobacterial bloom. High-throughput sequencing was used to determine the drivers of cyanobacteria blooms in nature. Multiple functions and interactions important to consider in cyanobacterial bloom ecology were identified. The microbial biodiversity of blooms revealed microbial functions, genomic characteristics, and interactions between cyanobacterial populations that could be involved in bloom stability and more coherently define cyanobacteria blooms. Our results highlight the importance of considering cyanobacterial blooms as a microbial ecosystem to predict, prevent, and mitigate them.
{"title":"Microbial diversity, genomics, and phage-host interactions of cyanobacterial harmful algal blooms.","authors":"Lauren E Krausfeldt, Elizaveta Shmakova, Hyo Won Lee, Viviana Mazzei, Keith A Loftin, Robert P Smith, Emily Karwacki, P Eric Fortman, Barry H Rosen, Hidetoshi Urakawa, Manoj Dadlani, Rita R Colwell, Jose V Lopez","doi":"10.1128/msystems.00709-23","DOIUrl":"10.1128/msystems.00709-23","url":null,"abstract":"<p><p>The occurrence of cyanobacterial harmful algal blooms (cyanoHABs) is related to their physical and chemical environment. However, less is known about their associated microbial interactions and processes. In this study, cyanoHABs were analyzed as a microbial ecosystem, using 1 year of 16S rRNA sequencing and 70 metagenomes collected during the bloom season from Lake Okeechobee (Florida, USA). Biogeographical patterns observed in microbial community composition and function reflected ecological zones distinct in their physical and chemical parameters that resulted in bloom \"hotspots\" near major lake inflows. Changes in relative abundances of taxa within multiple phyla followed increasing bloom severity. Functional pathways that correlated with increasing bloom severity encoded organic nitrogen and phosphorus utilization, storage of nutrients, exchange of genetic material, phage defense, and protection against oxidative stress, suggesting that microbial interactions may promote cyanoHAB resilience. Cyanobacterial communities were highly diverse, with picocyanobacteria ubiquitous and oftentimes most abundant, especially in the absence of blooms. The identification of novel bloom-forming cyanobacteria and genomic comparisons indicated a functionally diverse cyanobacterial community with differences in its capability to store nitrogen using cyanophycin and to defend against phage using CRISPR and restriction-modification systems. Considering blooms in the context of a microbial ecosystem and their interactions in nature, physiologies and interactions supporting the proliferation and stability of cyanoHABs are proposed, including a role for phage infection of picocyanobacteria. This study displayed the power of \"-omics\" to reveal important biological processes that could support the effective management and prediction of cyanoHABs.</p><p><strong>Importance: </strong>Cyanobacterial harmful algal blooms pose a significant threat to aquatic ecosystems and human health. Although physical and chemical conditions in aquatic systems that facilitate bloom development are well studied, there are fundamental gaps in the biological understanding of the microbial ecosystem that makes a cyanobacterial bloom. High-throughput sequencing was used to determine the drivers of cyanobacteria blooms in nature. Multiple functions and interactions important to consider in cyanobacterial bloom ecology were identified. The microbial biodiversity of blooms revealed microbial functions, genomic characteristics, and interactions between cyanobacterial populations that could be involved in bloom stability and more coherently define cyanobacteria blooms. Our results highlight the importance of considering cyanobacterial blooms as a microbial ecosystem to predict, prevent, and mitigate them.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Corynebacterium pseudotuberculosis (C. p), a facultative intracellular bacterium, is an important zoonotic pathogen that causes abscesses and pyogenic granulomas. The relationship between gut microbiota and host health or diseases has received increasing attention. However, the role of gut microbiota in the process of C. p infection is still unclear. In this study, we established a C. p infection model in C57BL/6 mice and examined the impact of preemptive oral administration Lactobacillus acidophilus (L. acidophilus) on infection. Our findings revealed that C. p infection led to pronounced pathological alterations in the liver and kidneys, characterized by abscess formation, intense inflammatory responses, and bacterial overload. Remarkably, these deleterious effects were greatly relieved by oral administration of L. acidophilus before infection with C. p. Additionally, we further found that during C. p infection, peritoneal macrophages (PMs) of mice orally administered with L. acidophilus accumulated more rapidly at sites of infection. Furthermore, our results showed that PMs from mice with oral L. acidophilus administration showed a stronger C. p clearance effect, and this was mediated by high expression of LC3-II protein. Meanwhile, oral administration of L. acidophilus protected the gut microbiota disorder in C57BL/6 mice caused by C. p infection. In summary, our study demonstrates that oral administration of L. acidophilus confers effective protection against C. p infection in C57BL/6 mice by modulating macrophage autophagy, thereby augmenting bacterial clearance and preserving gut microbiota and function stability. These findings position L. acidophilus as a viable probiotic candidate for the clinical prevention of C. p infection.
Importance: Corynebacterium pseudotuberculosis (C. p) is known to induce a range of chronic diseases in both animals and humans. Currently, clinical treatment for C. p infection mainly relies on antibiotic therapy or surgical intervention. However, excessive use of antibiotics may increase the risk of drug-resistant strains, and the effectiveness of treatment remains unsatisfactory. Furthermore, surgical procedures do not completely eradicate pathogens and can easily cause environmental pollution. Probiotic interventions are receiving increasing attention for improving the body's immune system and maintaining health. In this study, we established a C. p infection model in C57BL/6 mice to explore the impact of Lactobacillus acidophilus during C. p infection. Our results showed that L. acidophilus effectively protected against C. p infection by regulating the autophagy of macrophages and maintaining intestinal microbiota homeostasis. This study may provide a new strategy for the prevention of C. p
假结核棒状杆菌(Corynebacterium pseudotuberculosis,C. p)是一种兼性细胞内细菌,是一种重要的人畜共患病原体,可引起脓肿和化脓性肉芽肿。肠道微生物群与宿主健康或疾病之间的关系日益受到关注。然而,肠道微生物群在 C. p. 感染过程中的作用仍不清楚。在本研究中,我们在 C57BL/6 小鼠中建立了嗜酸乳杆菌感染模型,并研究了预先口服嗜酸乳杆菌对感染的影响。我们的研究结果表明,C. p感染会导致肝脏和肾脏发生明显的病理改变,其特点是脓肿形成、强烈的炎症反应和细菌超载。值得注意的是,在感染 C. p.之前口服嗜酸乳杆菌可大大缓解这些有害影响。此外,我们进一步发现,在 C. p.感染期间,口服嗜酸乳杆菌的小鼠腹腔巨噬细胞(PMs)在感染部位聚集得更快。此外,我们的研究结果表明,口服嗜酸乳杆菌的小鼠腹腔巨噬细胞具有更强的C. p清除效果,而这是由LC3-II蛋白的高表达所介导的。同时,口服嗜酸乳杆菌可保护C57BL/6小鼠因C. p感染而导致的肠道微生物群紊乱。总之,我们的研究表明,口服嗜酸乳杆菌可通过调节巨噬细胞自噬作用有效保护C57BL/6小鼠免受C. p感染,从而提高细菌清除率并保护肠道微生物群和功能稳定性。这些发现将嗜酸乳杆菌定位为临床预防假丝酵母感染的一种可行的候选益生菌:众所周知,假结核棒状杆菌(C. p)会诱发动物和人类的一系列慢性疾病。目前,假丝酵母菌感染的临床治疗主要依靠抗生素治疗或手术干预。然而,过度使用抗生素可能会增加耐药菌株的风险,而且治疗效果仍不尽如人意。此外,外科手术并不能完全根除病原体,而且容易造成环境污染。益生菌干预措施在改善人体免疫系统和维护健康方面正受到越来越多的关注。在本研究中,我们在 C57BL/6 小鼠中建立了梭状芽孢杆菌感染模型,以探讨嗜酸乳杆菌在梭状芽孢杆菌感染过程中的影响。结果表明,嗜酸乳杆菌通过调节巨噬细胞的自噬和维持肠道微生物群的平衡,有效地防止了 C. p 的感染。这项研究可为预防嗜酸乳杆菌感染提供一种新策略。
{"title":"<i>Lactobacillus acidophilus</i> protects against <i>Corynebacterium pseudotuberculosis</i> infection by regulating the autophagy of macrophages and maintaining gut microbiota homeostasis in C57BL/6 mice.","authors":"Dengliang Li, Yuecai Jiang, Zhanding Cui, Mengzhen Ma, Fang Zhu, Guanhua Li, Haoyue Yang, Shaofei Li, Tianliang Zhang, Dekun Chen, Wentao Ma","doi":"10.1128/msystems.00484-24","DOIUrl":"10.1128/msystems.00484-24","url":null,"abstract":"<p><p><i>Corynebacterium pseudotuberculosis</i> (<i>C. p</i>), a facultative intracellular bacterium, is an important zoonotic pathogen that causes abscesses and pyogenic granulomas. The relationship between gut microbiota and host health or diseases has received increasing attention. However, the role of gut microbiota in the process of <i>C. p</i> infection is still unclear. In this study, we established a <i>C. p</i> infection model in C57BL/6 mice and examined the impact of preemptive oral administration <i>Lactobacillus acidophilus</i> (<i>L. acidophilus</i>) on infection. Our findings revealed that <i>C. p</i> infection led to pronounced pathological alterations in the liver and kidneys, characterized by abscess formation, intense inflammatory responses, and bacterial overload. Remarkably, these deleterious effects were greatly relieved by oral administration of <i>L. acidophilus</i> before infection with <i>C. p</i>. Additionally, we further found that during <i>C. p</i> infection, peritoneal macrophages (PMs) of mice orally administered with <i>L. acidophilus</i> accumulated more rapidly at sites of infection. Furthermore, our results showed that PMs from mice with oral <i>L. acidophilus</i> administration showed a stronger <i>C. p</i> clearance effect, and this was mediated by high expression of LC3-II protein. Meanwhile, oral administration of <i>L. acidophilus</i> protected the gut microbiota disorder in C57BL/6 mice caused by <i>C. p</i> infection. In summary, our study demonstrates that oral administration of <i>L. acidophilus</i> confers effective protection against <i>C. p</i> infection in C57BL/6 mice by modulating macrophage autophagy, thereby augmenting bacterial clearance and preserving gut microbiota and function stability. These findings position <i>L. acidophilus</i> as a viable probiotic candidate for the clinical prevention of <i>C. p</i> infection.</p><p><strong>Importance: </strong><i>Corynebacterium pseudotuberculosis</i> (C. <i>p</i>) is known to induce a range of chronic diseases in both animals and humans. Currently, clinical treatment for C. <i>p</i> infection mainly relies on antibiotic therapy or surgical intervention. However, excessive use of antibiotics may increase the risk of drug-resistant strains, and the effectiveness of treatment remains unsatisfactory. Furthermore, surgical procedures do not completely eradicate pathogens and can easily cause environmental pollution. Probiotic interventions are receiving increasing attention for improving the body's immune system and maintaining health. In this study, we established a C. <i>p</i> infection model in C57BL/6 mice to explore the impact of <i>Lactobacillus</i> acidophilus during C. <i>p</i> infection. Our results showed that <i>L. acidophilus</i> effectively protected against C. <i>p</i> infection by regulating the autophagy of macrophages and maintaining intestinal microbiota homeostasis. This study may provide a new strategy for the prevention of C. <i>p</","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-07-23Epub Date: 2024-06-27DOI: 10.1128/msystems.00516-24
Renee E Oles, Marvic Carrillo Terrazas, Luke R Loomis, Chia-Yun Hsu, Caitlin Tribelhorn, Pedro Belda-Ferre, Allison C Ea, MacKenzie Bryant, Jocelyn A Young, Hannah C Carrow, William J Sandborn, Parambir S Dulai, Mamata Sivagnanam, David Pride, Rob Knight, Hiutung Chu
Bacteroides fragilis is a Gram-negative commensal bacterium commonly found in the human colon, which differentiates into two genomospecies termed divisions I and II. Through a comprehensive collection of 694 B. fragilis whole genome sequences, we identify novel features distinguishing these divisions. Our study reveals a distinct geographic distribution with division I strains predominantly found in North America and division II strains in Asia. Additionally, division II strains are more frequently associated with bloodstream infections, suggesting a distinct pathogenic potential. We report differences between the two divisions in gene abundance related to metabolism, virulence, stress response, and colonization strategies. Notably, division II strains harbor more antimicrobial resistance (AMR) genes than division I strains. These findings offer new insights into the functional roles of division I and II strains, indicating specialized niches within the intestine and potential pathogenic roles in extraintestinal sites.
Importance: Understanding the distinct functions of microbial species in the gut microbiome is crucial for deciphering their impact on human health. Classifying division II strains as Bacteroides fragilis can lead to erroneous associations, as researchers may mistakenly attribute characteristics observed in division II strains to the more extensively studied division I B. fragilis. Our findings underscore the necessity of recognizing these divisions as separate species with distinct functions. We unveil new findings of differential gene prevalence between division I and II strains in genes associated with intestinal colonization and survival strategies, potentially influencing their role as gut commensals and their pathogenicity in extraintestinal sites. Despite the significant niche overlap and colonization patterns between these groups, our study highlights the complex dynamics that govern strain distribution and behavior, emphasizing the need for a nuanced understanding of these microorganisms.
脆弱拟杆菌(Bacteroides fragilis)是一种常见于人类结肠的革兰氏阴性共生菌,分为两个基因组种,分别称为 I 和 II。通过全面收集 694 个脆弱拟杆菌全基因组序列,我们发现了区分这两个分支的新特征。我们的研究揭示了其独特的地理分布,I分部菌株主要分布在北美,II分部菌株主要分布在亚洲。此外,II 部菌株更常见于血液感染,这表明它们具有不同的致病潜力。我们报告了两个分部在新陈代谢、毒力、应激反应和定殖策略方面的基因丰度差异。值得注意的是,II 部菌株比 I 部菌株携带更多抗菌素耐药性(AMR)基因。这些发现为了解 I 部和 II 部菌株的功能作用提供了新的视角,表明了它们在肠道内的特殊生态位以及在肠道外的潜在致病作用:重要意义:了解肠道微生物组中微生物物种的不同功能对于解读它们对人类健康的影响至关重要。将第二分部菌株归类为脆弱拟杆菌可能会导致错误的关联,因为研究人员可能会错误地将在第二分部菌株中观察到的特征归因于研究更为广泛的第一分部脆弱拟杆菌。我们的研究结果强调,有必要将这些分部视为具有不同功能的独立物种。我们揭示了新的发现,即在与肠道定殖和生存策略相关的基因中,I 部和 II 部菌株的基因流行率不同,这可能会影响它们作为肠道共生菌的角色及其在肠道外的致病性。尽管这两类菌株之间存在明显的生态位重叠和定植模式,但我们的研究强调了制约菌株分布和行为的复杂动态,强调了对这些微生物进行细致入微的了解的必要性。
{"title":"Pangenome comparison of <i>Bacteroides fragilis</i> genomospecies unveils genetic diversity and ecological insights.","authors":"Renee E Oles, Marvic Carrillo Terrazas, Luke R Loomis, Chia-Yun Hsu, Caitlin Tribelhorn, Pedro Belda-Ferre, Allison C Ea, MacKenzie Bryant, Jocelyn A Young, Hannah C Carrow, William J Sandborn, Parambir S Dulai, Mamata Sivagnanam, David Pride, Rob Knight, Hiutung Chu","doi":"10.1128/msystems.00516-24","DOIUrl":"10.1128/msystems.00516-24","url":null,"abstract":"<p><p><i>Bacteroides fragilis</i> is a Gram-negative commensal bacterium commonly found in the human colon, which differentiates into two genomospecies termed divisions I and II. Through a comprehensive collection of 694 <i>B. fragilis</i> whole genome sequences, we identify novel features distinguishing these divisions. Our study reveals a distinct geographic distribution with division I strains predominantly found in North America and division II strains in Asia. Additionally, division II strains are more frequently associated with bloodstream infections, suggesting a distinct pathogenic potential. We report differences between the two divisions in gene abundance related to metabolism, virulence, stress response, and colonization strategies. Notably, division II strains harbor more antimicrobial resistance (AMR) genes than division I strains. These findings offer new insights into the functional roles of division I and II strains, indicating specialized niches within the intestine and potential pathogenic roles in extraintestinal sites.</p><p><strong>Importance: </strong>Understanding the distinct functions of microbial species in the gut microbiome is crucial for deciphering their impact on human health. Classifying division II strains as <i>Bacteroides fragilis</i> can lead to erroneous associations, as researchers may mistakenly attribute characteristics observed in division II strains to the more extensively studied division I <i>B. fragilis</i>. Our findings underscore the necessity of recognizing these divisions as separate species with distinct functions. We unveil new findings of differential gene prevalence between division I and II strains in genes associated with intestinal colonization and survival strategies, potentially influencing their role as gut commensals and their pathogenicity in extraintestinal sites. Despite the significant niche overlap and colonization patterns between these groups, our study highlights the complex dynamics that govern strain distribution and behavior, emphasizing the need for a nuanced understanding of these microorganisms.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-07-23Epub Date: 2024-07-03DOI: 10.1128/msystems.00556-24
Robyn L Prueitt, Julie E Goodman
{"title":"Real-world bisphenol A exposure not linked to microbiota dynamics in childhood obesity.","authors":"Robyn L Prueitt, Julie E Goodman","doi":"10.1128/msystems.00556-24","DOIUrl":"10.1128/msystems.00556-24","url":null,"abstract":"","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Skin ulceration syndrome (SUS) is currently the main disease threatening Apostichopus japonicus aquaculture due to its higher mortality rate and infectivity, which is caused by Vibrio splendidus. Our previous studies have demonstrated that SUS is accompanied by intestinal microbiota (IM) dysbiosis, alteration of short-chain fatty acids (SCFAs) content and the damage to the intestinal barrier. However, the mediating effect of IM on intestine dysfunction is largely unknown. Herein, we conducted comprehensive intestinal microbiota transplantation (IMT) to explore the link between IM and SUS development. Furthermore, we isolated and identified a Bacillus coagulans strain with an ability to produce acetic acid from both healthy individual and SUS individual with IM from healthy donors. We found that dysbiotic IM and intestinal barrier function in SUS recipients A. japonicus could be restored by IM from healthy donors. The B. coagulans strain could restore IM community and intestinal barrier function. Consistently, acetate supply also restores intestinal homeostasis of SUS-diseased and V. splendidus-infected A. japonicus. Mechanically, acetate was found to specifically bind to its receptor-free fatty acid receptor 2 (FFAR2) to mediate IM structure community and intestinal barrier function. Knockdown of FFAR2 by transfection of specific FFAR2 siRNA could hamper acetate-mediated intestinal homeostasis in vivo. Furthermore, we confirmed that acetate/FFAR2 could inhibit V. splendidus-activated NF-κB-MLCK-MLC signaling pathway to restore intestinal epithelium integrity and upregulated the expression of ZO-1 and Occludin. Our findings provide the first evidence that B. coagulans restores pathogen-induced intestinal barrier dysfunction via acetate/FFAR2-NF-κB-MLCK-MLC axis, which provides new insights into the control and prevention of SUS outbreak from an ecological perspective.IMPORTANCESkin ulceration syndrome (SUS) as a main disease in Apostichopus japonicus aquaculture has severely restricted the developmental A. japonicus aquaculture industry. Intestinal microbiota (IM) has been studied extensively due to its immunomodulatory properties. Short-chain fatty acids (SCFAs) as an essential signal molecule for microbial regulation of host health also have attracted wide attention. Therefore, it is beneficial to explore the link between IM and SUS for prevention and control of SUS. In the study, the contribution of IM to SUS development has been examined. Additionally, our research further validated the restoration of SCFAs on intestinal barrier dysfunction caused by SUS via isolating SCFAs-producing bacteria. Notably, this restoration might be achieved by inhibition of NF-κB-MLCK-MLC signal pathway, which could be activated by V. splendidus. These findings may have important implications for exploration of the role of IM in SUS occurrence and provide insight into
皮肤溃疡综合征(SUS)是目前威胁日本狎鸥鱼养殖的主要疾病,因其死亡率和感染性较高,由绚丽弧菌引起。我们之前的研究表明,SUS伴随着肠道微生物群(IM)失调、短链脂肪酸(SCFAs)含量的改变和肠道屏障的破坏。然而,IM 对肠道功能障碍的介导作用在很大程度上是未知的。在此,我们进行了全面的肠道微生物群移植(IMT),以探索 IM 与 SUS 发生之间的联系。此外,我们还从健康个体和SUS个体的健康供体中分离并鉴定出了具有产生醋酸能力的凝结芽孢杆菌菌株。我们发现,健康供体的 IM 可以恢复 SUS 受体 A. japonicus 中菌群失调的 IM 和肠道屏障功能。凝结芽孢杆菌菌株可以恢复肠内生物群落和肠道屏障功能。同样,醋酸盐也能恢复 SUS 疾病和白芨感染的日本豚鼠的肠道平衡。在机制上,研究发现醋酸与其无受体的脂肪酸受体 2(FFAR2)特异性结合,以介导 IM 结构群落和肠屏障功能。通过转染特异性 FFAR2 siRNA 来敲除 FFAR2 可阻碍醋酸介导的体内肠道平衡。此外,我们还证实醋酸/FFAR2能抑制白芨激活的NF-κB-MLCK-MLC信号通路,从而恢复肠上皮细胞的完整性,并上调ZO-1和Occludin的表达。我们的研究结果首次证明了凝结芽孢杆菌可通过醋酸酯/FFAR2-NF-κB-MLCK-MLC 轴恢复病原体诱导的肠屏障功能障碍,这为从生态学角度控制和预防 SUS 的爆发提供了新的见解。 重要意义皮肤溃疡综合征(SUS)作为日本狎鸥鱼养殖过程中的一种主要疾病,严重制约了日本狎鸥鱼养殖业的发展。肠道微生物群(IM)因其免疫调节特性而被广泛研究。短链脂肪酸(SCFAs)作为微生物调节宿主健康的重要信号分子也引起了广泛关注。因此,探讨 IM 与 SUS 之间的联系有利于预防和控制 SUS。本研究探讨了 IM 对 SUS 发展的贡献。此外,我们的研究还通过分离产生 SCFAs 的细菌,进一步验证了 SCFAs 对 SUS 引起的肠屏障功能障碍的修复作用。值得注意的是,这种修复作用可能是通过抑制芨芨草菌激活的 NF-κB-MLCK-MLC 信号通路实现的。这些发现可能对探索 IM 在 SUS 发生中的作用具有重要意义,并为 SUS 的治疗提供了启示。
{"title":"<i>Bacillus coagulans</i> restores pathogen-induced intestinal dysfunction via acetate-FFAR2-NF-κB-MLCK-MLC axis in <i>Apostichopus japonicus</i>.","authors":"Mingshan Song, Shanshan Zhang, Zhen Zhang, Liyuan Guo, Weikang Liang, Chenghua Li, Zhonghua Wang","doi":"10.1128/msystems.00602-24","DOIUrl":"10.1128/msystems.00602-24","url":null,"abstract":"<p><p>Skin ulceration syndrome (SUS) is currently the main disease threatening <i>Apostichopus japonicus</i> aquaculture due to its higher mortality rate and infectivity, which is caused by <i>Vibrio splendidus</i>. Our previous studies have demonstrated that SUS is accompanied by intestinal microbiota (IM) dysbiosis, alteration of short-chain fatty acids (SCFAs) content and the damage to the intestinal barrier. However, the mediating effect of IM on intestine dysfunction is largely unknown. Herein, we conducted comprehensive intestinal microbiota transplantation (IMT) to explore the link between IM and SUS development. Furthermore, we isolated and identified a <i>Bacillus coagulans</i> strain with an ability to produce acetic acid from both healthy individual and SUS individual with IM from healthy donors. We found that dysbiotic IM and intestinal barrier function in SUS recipients <i>A. japonicus</i> could be restored by IM from healthy donors. The <i>B. coagulans</i> strain could restore IM community and intestinal barrier function. Consistently, acetate supply also restores intestinal homeostasis of SUS-diseased and <i>V. splendidus</i>-infected <i>A. japonicus</i>. Mechanically, acetate was found to specifically bind to its receptor-free fatty acid receptor 2 (FFAR2) to mediate IM structure community and intestinal barrier function. Knockdown of FFAR2 by transfection of specific FFAR2 siRNA could hamper acetate-mediated intestinal homeostasis <i>in vivo</i>. Furthermore, we confirmed that acetate/FFAR2 could inhibit <i>V. splendidus</i>-activated NF-κB-MLCK-MLC signaling pathway to restore intestinal epithelium integrity and upregulated the expression of ZO-1 and Occludin. Our findings provide the first evidence that <i>B. coagulans</i> restores pathogen-induced intestinal barrier dysfunction via acetate/FFAR2-NF-κB-MLCK-MLC axis, which provides new insights into the control and prevention of SUS outbreak from an ecological perspective.IMPORTANCESkin ulceration syndrome (SUS) as a main disease in <i>Apostichopus japonicus</i> aquaculture has severely restricted the developmental <i>A. japonicus</i> aquaculture industry. Intestinal microbiota (IM) has been studied extensively due to its immunomodulatory properties. Short-chain fatty acids (SCFAs) as an essential signal molecule for microbial regulation of host health also have attracted wide attention. Therefore, it is beneficial to explore the link between IM and SUS for prevention and control of SUS. In the study, the contribution of IM to SUS development has been examined. Additionally, our research further validated the restoration of SCFAs on intestinal barrier dysfunction caused by SUS via isolating SCFAs-producing bacteria. Notably, this restoration might be achieved by inhibition of NF-κB-MLCK-MLC signal pathway, which could be activated by <i>V. splendidus</i>. These findings may have important implications for exploration of the role of IM in SUS occurrence and provide insight into ","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}