Pub Date : 2024-09-17Epub Date: 2024-08-19DOI: 10.1128/msystems.00736-24
Yujiro Hirose, Daniel C Zielinski, Saugat Poudel, Kevin Rychel, Jonathon L Baker, Yoshihiro Toya, Masaya Yamaguchi, Almut Heinken, Ines Thiele, Shigetada Kawabata, Bernhard O Palsson, Victor Nizet
Streptococcus pyogenes is responsible for a range of diseases in humans contributing significantly to morbidity and mortality. Among more than 200 serotypes of S. pyogenes, serotype M1 strains hold the greatest clinical relevance due to their high prevalence in severe human infections. To enhance our understanding of pathogenesis and discovery of potential therapeutic approaches, we have developed the first genome-scale metabolic model (GEM) for a serotype M1 S. pyogenes strain, which we name iYH543. The curation of iYH543 involved cross-referencing a draft GEM of S. pyogenes serotype M1 from the AGORA2 database with gene essentiality and autotrophy data obtained from transposon mutagenesis-based and growth screens. We achieved a 92.6% (503/543 genes) accuracy in predicting gene essentiality and a 95% (19/20 amino acids) accuracy in predicting amino acid auxotrophy. Additionally, Biolog Phenotype microarrays were employed to examine the growth phenotypes of S. pyogenes, which further contributed to the refinement of iYH543. Notably, iYH543 demonstrated 88% accuracy (168/190 carbon sources) in predicting growth on various sole carbon sources. Discrepancies observed between iYH543 and the actual behavior of living S. pyogenes highlighted areas of uncertainty in the current understanding of S. pyogenes metabolism. iYH543 offers novel insights and hypotheses that can guide future research efforts and ultimately inform novel therapeutic strategies.IMPORTANCEGenome-scale models (GEMs) play a crucial role in investigating bacterial metabolism, predicting the effects of inhibiting specific metabolic genes and pathways, and aiding in the identification of potential drug targets. Here, we have developed the first GEM for the S. pyogenes highly virulent serotype, M1, which we name iYH543. The iYH543 achieved high accuracy in predicting gene essentiality. We also show that the knowledge obtained by substituting actual measurement values for iYH543 helps us gain insights that connect metabolism and virulence. iYH543 will serve as a useful tool for rational drug design targeting S. pyogenes metabolism and computational screening to investigate the interplay between inhibiting virulence factor synthesis and growth.
{"title":"A genome-scale metabolic model of a globally disseminated hyperinvasive M1 strain of <i>Streptococcus pyogenes</i>.","authors":"Yujiro Hirose, Daniel C Zielinski, Saugat Poudel, Kevin Rychel, Jonathon L Baker, Yoshihiro Toya, Masaya Yamaguchi, Almut Heinken, Ines Thiele, Shigetada Kawabata, Bernhard O Palsson, Victor Nizet","doi":"10.1128/msystems.00736-24","DOIUrl":"10.1128/msystems.00736-24","url":null,"abstract":"<p><p><i>Streptococcus pyogenes</i> is responsible for a range of diseases in humans contributing significantly to morbidity and mortality. Among more than 200 serotypes of <i>S. pyogenes</i>, serotype M1 strains hold the greatest clinical relevance due to their high prevalence in severe human infections. To enhance our understanding of pathogenesis and discovery of potential therapeutic approaches, we have developed the first genome-scale metabolic model (GEM) for a serotype M1 <i>S. pyogenes</i> strain, which we name iYH543. The curation of iYH543 involved cross-referencing a draft GEM of <i>S. pyogenes</i> serotype M1 from the AGORA2 database with gene essentiality and autotrophy data obtained from transposon mutagenesis-based and growth screens. We achieved a 92.6% (503/543 genes) accuracy in predicting gene essentiality and a 95% (19/20 amino acids) accuracy in predicting amino acid auxotrophy. Additionally, Biolog Phenotype microarrays were employed to examine the growth phenotypes of <i>S. pyogenes,</i> which further contributed to the refinement of iYH543. Notably, iYH543 demonstrated 88% accuracy (168/190 carbon sources) in predicting growth on various sole carbon sources. Discrepancies observed between iYH543 and the actual behavior of living <i>S. pyogenes</i> highlighted areas of uncertainty in the current understanding of <i>S. pyogenes</i> metabolism. iYH543 offers novel insights and hypotheses that can guide future research efforts and ultimately inform novel therapeutic strategies.IMPORTANCEGenome-scale models (GEMs) play a crucial role in investigating bacterial metabolism, predicting the effects of inhibiting specific metabolic genes and pathways, and aiding in the identification of potential drug targets. Here, we have developed the first GEM for the <i>S. pyogenes</i> highly virulent serotype, M1, which we name iYH543. The iYH543 achieved high accuracy in predicting gene essentiality. We also show that the knowledge obtained by substituting actual measurement values for iYH543 helps us gain insights that connect metabolism and virulence. iYH543 will serve as a useful tool for rational drug design targeting <i>S. pyogenes</i> metabolism and computational screening to investigate the interplay between inhibiting virulence factor synthesis and growth.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0073624"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000350","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 : 2024-09-17Epub Date: 2024-08-19DOI: 10.1128/msystems.00242-24
Lauren M Lui, Torben N Nielsen
Although long-read sequencing has enabled obtaining high-quality and complete genomes from metagenomes, many challenges still remain to completely decompose a metagenome into its constituent prokaryotic and viral genomes. This study focuses on decomposing an estuarine metagenome to obtain a more accurate estimate of microbial diversity. To achieve this, we developed a new bead-based DNA extraction method, a novel bin refinement method, and obtained 150 Gbp of Nanopore sequencing. We estimate that there are ~500 bacterial and archaeal species in our sample and obtained 68 high-quality bins (>90% complete, <5% contamination, ≤5 contigs, contig length of >100 kbp, and all ribosomal and tRNA genes). We also obtained many contigs of picoeukaryotes, environmental DNA of larger eukaryotes such as mammals, and complete mitochondrial and chloroplast genomes and detected ~40,000 viral populations. Our analysis indicates that there are only a few strains that comprise most of the species abundances.
Importance: Ocean and estuarine microbiomes play critical roles in global element cycling and ecosystem function. Despite the importance of these microbial communities, many species still have not been cultured in the lab. Environmental sequencing is the primary way the function and population dynamics of these communities can be studied. Long-read sequencing provides an avenue to overcome limitations of short-read technologies to obtain complete microbial genomes but comes with its own technical challenges, such as needed sequencing depth and obtaining high-quality DNA. We present here new sampling and bioinformatics methods to attempt decomposing an estuarine microbiome into its constituent genomes. Our results suggest there are only a few strains that comprise most of the species abundances from viruses to picoeukaryotes, and to fully decompose a metagenome of this diversity requires 1 Tbp of long-read sequencing. We anticipate that as long-read sequencing technologies continue to improve, less sequencing will be needed.
尽管长线程测序技术已经能够从元基因组中获得高质量的完整基因组,但要将元基因组完全分解为其组成的原核生物和病毒基因组,仍然存在许多挑战。本研究的重点是分解河口元基因组,以便更准确地估计微生物的多样性。为此,我们开发了一种新的基于珠子的 DNA 提取方法和一种新的 bin 细化方法,并获得了 150 Gbp 的 Nanopore 测序结果。我们估计样本中有约 500 个细菌和古细菌物种,并获得了 68 个高质量 bins(>90% 完整、100 kbp、所有核糖体和 tRNA 基因)。我们还获得了许多皮核生物的等位基因、哺乳动物等大型真核生物的环境 DNA 以及完整的线粒体和叶绿体基因组,并检测到约 4 万个病毒种群。我们的分析表明,只有少数菌株构成了大部分物种的丰度:海洋和河口微生物群在全球元素循环和生态系统功能中发挥着关键作用。尽管这些微生物群落非常重要,但许多物种仍未在实验室中培养出来。环境测序是研究这些群落的功能和种群动态的主要方法。长线程测序为克服短线程技术的局限性以获得完整的微生物基因组提供了一条途径,但也带来了自身的技术挑战,如所需的测序深度和获得高质量的 DNA。我们在此介绍新的取样和生物信息学方法,尝试将河口微生物组分解为其组成基因组。我们的研究结果表明,从病毒到皮核生物,只有少数几个菌株组成了大部分物种的丰度,而要完全分解如此多样性的元基因组,需要 1 Tbp 的长线程测序。我们预计,随着长线程测序技术的不断改进,所需的测序量将会减少。
{"title":"Decomposing a San Francisco estuary microbiome using long-read metagenomics reveals species- and strain-level dominance from picoeukaryotes to viruses.","authors":"Lauren M Lui, Torben N Nielsen","doi":"10.1128/msystems.00242-24","DOIUrl":"10.1128/msystems.00242-24","url":null,"abstract":"<p><p>Although long-read sequencing has enabled obtaining high-quality and complete genomes from metagenomes, many challenges still remain to completely decompose a metagenome into its constituent prokaryotic and viral genomes. This study focuses on decomposing an estuarine metagenome to obtain a more accurate estimate of microbial diversity. To achieve this, we developed a new bead-based DNA extraction method, a novel bin refinement method, and obtained 150 Gbp of Nanopore sequencing. We estimate that there are ~500 bacterial and archaeal species in our sample and obtained 68 high-quality bins (>90% complete, <5% contamination, ≤5 contigs, contig length of >100 kbp, and all ribosomal and tRNA genes). We also obtained many contigs of picoeukaryotes, environmental DNA of larger eukaryotes such as mammals, and complete mitochondrial and chloroplast genomes and detected ~40,000 viral populations. Our analysis indicates that there are only a few strains that comprise most of the species abundances.</p><p><strong>Importance: </strong>Ocean and estuarine microbiomes play critical roles in global element cycling and ecosystem function. Despite the importance of these microbial communities, many species still have not been cultured in the lab. Environmental sequencing is the primary way the function and population dynamics of these communities can be studied. Long-read sequencing provides an avenue to overcome limitations of short-read technologies to obtain complete microbial genomes but comes with its own technical challenges, such as needed sequencing depth and obtaining high-quality DNA. We present here new sampling and bioinformatics methods to attempt decomposing an estuarine microbiome into its constituent genomes. Our results suggest there are only a few strains that comprise most of the species abundances from viruses to picoeukaryotes, and to fully decompose a metagenome of this diversity requires 1 Tbp of long-read sequencing. We anticipate that as long-read sequencing technologies continue to improve, less sequencing will be needed.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0024224"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000351","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}
Methicillin-resistant Staphylococcus aureus (MRSA) sequence type 630 (ST630) is a rarely reported lineage worldwide. This study aimed to trace the dissemination of the emerging MRSA ST630 clones in China and investigate their virulence potential. We collected 22 ST630-MRSA isolates from across China and performed whole-genome sequencing analysis and virulence characterization on these isolates. Epidemiological results showed that MRSA ST630 isolates were primarily isolated from pus/wound secretions, mainly originating from Jiangxi province, and carried diverse virulence and drug resistance genes. Staphylococcal cassette chromosome mec type V (SCCmec V) predominated (11/22, 50.0%) among the MRSA ST630 isolates. Interestingly, nearly half (45.5%) of the 22 ST630-MRSA isolates tested lacked intact SCCmec elements. Phylogenetic analysis demonstrated that ST630-MRSA could be divided into two distinct clades, with widespread dissemination mainly in Chinese regions. Five representative isolates were selected for phenotypic assays, including hemolysin activity, real-time fluorescence quantitative PCR, western blot analysis, hydrogen peroxide killing assay, blood killing assay, cell adhesion and invasion assay, and mouse skin abscess model. The results showed that, compared to the USA300-LAC strain, ST630 isolates exhibited particularly strong invasiveness and virulence in the aforementioned phenotypic assays. This study described the emergence of a highly virulent ST630-MRSA lineage and improved our insight into the molecular epidemiology of ST630 clones in China.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) sequence type 630 (ST630) is an emerging clone with an increasing isolation rate in China. This study raises awareness of the hypervirulent MRSA ST630 clones in China and alerts people to their widespread dissemination. ST630-staphylococcal cassette chromosome mec V is a noteworthy clone in China, and we present the first comprehensive genetic and phenotypic analysis of this lineage. Our findings provide valuable insights for the prevention and control of infections caused by this emerging MRSA clone.
{"title":"Phenotypic and genomic analysis of the hypervirulent methicillin-resistant <i>Staphylococcus aureus</i> ST630 clone in China.","authors":"Junhong Shi, Yanghua Xiao, Li Shen, Cailing Wan, Bingjie Wang, Peiyao Zhou, Jiao Zhang, Weihua Han, Fangyou Yu","doi":"10.1128/msystems.00664-24","DOIUrl":"10.1128/msystems.00664-24","url":null,"abstract":"<p><p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) sequence type 630 (ST630) is a rarely reported lineage worldwide. This study aimed to trace the dissemination of the emerging MRSA ST630 clones in China and investigate their virulence potential. We collected 22 ST630-MRSA isolates from across China and performed whole-genome sequencing analysis and virulence characterization on these isolates. Epidemiological results showed that MRSA ST630 isolates were primarily isolated from pus/wound secretions, mainly originating from Jiangxi province, and carried diverse virulence and drug resistance genes. Staphylococcal cassette chromosome mec type V (SCCmec V) predominated (11/22, 50.0%) among the MRSA ST630 isolates. Interestingly, nearly half (45.5%) of the 22 ST630-MRSA isolates tested lacked intact SCCmec elements. Phylogenetic analysis demonstrated that ST630-MRSA could be divided into two distinct clades, with widespread dissemination mainly in Chinese regions. Five representative isolates were selected for phenotypic assays, including hemolysin activity, real-time fluorescence quantitative PCR, western blot analysis, hydrogen peroxide killing assay, blood killing assay, cell adhesion and invasion assay, and mouse skin abscess model. The results showed that, compared to the USA300-LAC strain, ST630 isolates exhibited particularly strong invasiveness and virulence in the aforementioned phenotypic assays. This study described the emergence of a highly virulent ST630-MRSA lineage and improved our insight into the molecular epidemiology of ST630 clones in China.IMPORTANCEMethicillin-resistant <i>Staphylococcus aureus</i> (MRSA) sequence type 630 (ST630) is an emerging clone with an increasing isolation rate in China. This study raises awareness of the hypervirulent MRSA ST630 clones in China and alerts people to their widespread dissemination. ST630-staphylococcal cassette chromosome mec V is a noteworthy clone in China, and we present the first comprehensive genetic and phenotypic analysis of this lineage. Our findings provide valuable insights for the prevention and control of infections caused by this emerging MRSA clone.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0066424"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000353","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 : 2024-09-17DOI: 10.1128/msystems.00585-24
Elizaveta VinogradovaNurislam MukhanbetzhanovMadiyar NurgaziyevZharkyn JarmukhanovRakhilya AipovaAliya SailybayevaMakhabbat BekbossynovaSamat KozhakhmetovAlmagul Kushugulova1Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan2Kazakh Research Institute of Soil Science and Agricultural Chemistry named after U.Uspanov, Almaty, Kazakhstan3JSC “National Research Cardiac Surgery Center”, Astana, KazakhstanVanni Bucci
mSystems, Ahead of Print.
mSystems, Ahead of Print.
{"title":"Impact of urbanization on gut microbiome mosaics across geographic and dietary contexts","authors":"Elizaveta VinogradovaNurislam MukhanbetzhanovMadiyar NurgaziyevZharkyn JarmukhanovRakhilya AipovaAliya SailybayevaMakhabbat BekbossynovaSamat KozhakhmetovAlmagul Kushugulova1Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan2Kazakh Research Institute of Soil Science and Agricultural Chemistry named after U.Uspanov, Almaty, Kazakhstan3JSC “National Research Cardiac Surgery Center”, Astana, KazakhstanVanni Bucci","doi":"10.1128/msystems.00585-24","DOIUrl":"https://doi.org/10.1128/msystems.00585-24","url":null,"abstract":"mSystems, Ahead of Print. <br/>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":"22 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1128/msystems.00626-24
Abel A. VlasblomBirgitta DuimShriram PatelRoosmarijn E. C. LuikenDaniel Crespo-PiazueloJulia EckenbergerChloe E. HuseyinPeadar G. LawlorChristian ElendJaap A. WagenaarMarcus J. ClaessonAldert L. Zomer1Faculty of Veterinary Medicine, Division of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands2WHO Collaborating Centre for Reference and Research on Campylobacter and Antimicrobial Resistance from a One Health Perspective/WOAH Reference Laboratory for Campylobacteriosis, Utrecht, The Netherlands3School of Microbiology and APC Microbiome Ireland, University College Cork, Cork, Ireland4SeqBiome Ltd., Cork, Ireland5Pig Development Department,Teagasc Animal & Grassland Research & Innovation Centre, Moorepark, Fermoy, Co. Cork, Ireland6EW Nutrition Innovation GmbH & Co.KG, Cologne, Germany7Wageningen Bioveterinary Research, Lelystad, The NetherlandsTricia A. Van Laar
mSystems, Ahead of Print.
mSystems, Ahead of Print.
{"title":"The developing pig respiratory microbiome harbors strains antagonistic to common respiratory pathogens","authors":"Abel A. VlasblomBirgitta DuimShriram PatelRoosmarijn E. C. LuikenDaniel Crespo-PiazueloJulia EckenbergerChloe E. HuseyinPeadar G. LawlorChristian ElendJaap A. WagenaarMarcus J. ClaessonAldert L. Zomer1Faculty of Veterinary Medicine, Division of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands2WHO Collaborating Centre for Reference and Research on Campylobacter and Antimicrobial Resistance from a One Health Perspective/WOAH Reference Laboratory for Campylobacteriosis, Utrecht, The Netherlands3School of Microbiology and APC Microbiome Ireland, University College Cork, Cork, Ireland4SeqBiome Ltd., Cork, Ireland5Pig Development Department,Teagasc Animal & Grassland Research & Innovation Centre, Moorepark, Fermoy, Co. Cork, Ireland6EW Nutrition Innovation GmbH & Co.KG, Cologne, Germany7Wageningen Bioveterinary Research, Lelystad, The NetherlandsTricia A. Van Laar","doi":"10.1128/msystems.00626-24","DOIUrl":"https://doi.org/10.1128/msystems.00626-24","url":null,"abstract":"mSystems, Ahead of Print. <br/>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":"17 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17Epub Date: 2024-08-21DOI: 10.1128/msystems.00434-24
Suet-Ying Kwan, Caroline M Sabotta, Lorenzo R Cruz, Matthew C Wong, Nadim J Ajami, Joseph B McCormick, Susan P Fisher-Hoch, Laura Beretta
Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of Inoviridae was associated with both diabetes and liver steatosis. Diabetes was further associated with the enrichment of predominantly temperate Escherichia phages, some of which possessed virulence factors. Liver steatosis was associated with the depletion of Lactococcus phages r1t and BK5-T, and enrichment of the globally prevalent Crassvirales phages, including members of genus cluster IX (Burzaovirus coli, Burzaovirus faecalis) and VI (Kahnovirus oralis). The Lactococcus phages showed strong correlations and co-occurrence with Lactococcus lactis, while the Crassvirales phages, B. coli, B. faecalis, and UAG-readthrough crAss clade correlated and co-occurred with Prevotella copri. In conclusion, we identified the gut phageome signatures for two closely linked metabolic diseases with significant global burden. These phage signatures may have utility in risk modeling and disease prevention in this high-risk population, and identification of potential bacterial targets for phage therapy.IMPORTANCEPhages influence human health and disease by shaping the gut bacterial community. Using stool samples from a high-risk Mexican American population, we provide insights into the gut phageome changes associated with diabetes and liver steatosis, two closely linked metabolic diseases with significant global burden. Common to both diseases was an enrichment of Inoviridae, a group of phages that infect bacterial hosts chronically without lysis, allowing them to significantly influence bacterial growth, virulence, motility, biofilm formation, and horizontal gene transfer. Diabetes was additionally associated with the enrichment of Escherichia coli-infecting phages, some of which contained virulence factors. Liver steatosis was additionally associated with the depletion of Lactococcus lactis-infecting phages, and enrichment of Crassvirales phages, a group of virulent phages with high global prevalence and persistence across generations. These phageome signatures may have utility in risk modeling, as well as identify potential bacterial targets for phage therapy.
{"title":"Gut phageome in Mexican Americans: a population at high risk for metabolic dysfunction-associated steatotic liver disease and diabetes.","authors":"Suet-Ying Kwan, Caroline M Sabotta, Lorenzo R Cruz, Matthew C Wong, Nadim J Ajami, Joseph B McCormick, Susan P Fisher-Hoch, Laura Beretta","doi":"10.1128/msystems.00434-24","DOIUrl":"10.1128/msystems.00434-24","url":null,"abstract":"<p><p>Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of <i>Inoviridae</i> was associated with both diabetes and liver steatosis. Diabetes was further associated with the enrichment of predominantly temperate <i>Escherichia</i> phages, some of which possessed virulence factors. Liver steatosis was associated with the depletion of <i>Lactococcus</i> phages r1t and BK5-T, and enrichment of the globally prevalent <i>Crassvirales</i> phages, including members of genus cluster IX (<i>Burzaovirus coli</i>, <i>Burzaovirus faecalis</i>) and VI (<i>Kahnovirus oralis</i>). The <i>Lactococcus</i> phages showed strong correlations and co-occurrence with <i>Lactococcus lactis</i>, while the <i>Crassvirales</i> phages, <i>B. coli</i>, <i>B. faecalis</i>, and UAG-readthrough crAss clade correlated and co-occurred with <i>Prevotella copri</i>. In conclusion, we identified the gut phageome signatures for two closely linked metabolic diseases with significant global burden. These phage signatures may have utility in risk modeling and disease prevention in this high-risk population, and identification of potential bacterial targets for phage therapy.IMPORTANCEPhages influence human health and disease by shaping the gut bacterial community. Using stool samples from a high-risk Mexican American population, we provide insights into the gut phageome changes associated with diabetes and liver steatosis, two closely linked metabolic diseases with significant global burden. Common to both diseases was an enrichment of <i>Inoviridae</i>, a group of phages that infect bacterial hosts chronically without lysis, allowing them to significantly influence bacterial growth, virulence, motility, biofilm formation, and horizontal gene transfer. Diabetes was additionally associated with the enrichment of <i>Escherichia coli</i>-infecting phages, some of which contained virulence factors. Liver steatosis was additionally associated with the depletion of <i>Lactococcus lactis</i>-infecting phages, and enrichment of <i>Crassvirales</i> phages, a group of virulent phages with high global prevalence and persistence across generations. These phageome signatures may have utility in risk modeling, as well as identify potential bacterial targets for phage therapy.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0043424"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018072","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 : 2024-09-17Epub Date: 2024-08-27DOI: 10.1128/msystems.00706-24
Karel Kopejtka, Jürgen Tomasch, Sahana Shivaramu, Mohit Kumar Saini, David Kaftan, Michal Koblížek
The first phototrophic member of the bacterial phylum Gemmatimonadota, Gemmatimonas phototrophica AP64T, received all its photosynthesis genes via distant horizontal gene transfer from a purple bacterium. Here, we investigated how these acquired genes, which are tightly controlled by oxygen and light in the ancestor, are integrated into the regulatory system of its new host. G. phototrophica grew well under aerobic and semiaerobic conditions, with almost no difference in gene expression. Under aerobic conditions, the growth of G. phototrophica was optimal at 80 µmol photon m-2 s-1, while higher light intensities had an inhibitory effect. The transcriptome showed only a minimal response to the dark-light shift at optimal light intensity, while the exposure to a higher light intensity (200 µmol photon m-2 s-1) induced already stronger but still transient changes in gene expression. Interestingly, a singlet oxygen defense was not activated under any conditions tested. Our results indicate that G. phototrophica possesses neither the oxygen-dependent repression of photosynthesis genes known from purple bacteria nor the light-dependent repression described in aerobic anoxygenic phototrophs. Instead, G. phototrophica has evolved as a low-light species preferring reduced oxygen concentrations. Under these conditions, the bacterium can safely employ its photoheterotrophic metabolism without the need for complex regulatory mechanisms.
Importance: Horizontal gene transfer is one of the main mechanisms by which bacteria acquire new genes. However, it represents only the first step as the transferred genes have also to be functionally and regulatory integrated into the recipient's cellular machinery. Gemmatimonas phototrophica, a member of bacterial phylum Gemmatimonadota, acquired its photosynthesis genes via distant horizontal gene transfer from a purple bacterium. Thus, it represents a unique natural experiment, in which the entire package of photosynthesis genes was transplanted into a distant host. We show that G. phototrophica lacks the regulation of photosynthesis gene expressions in response to oxygen concentration and light intensity that are common in purple bacteria. This restricts its growth to low-light habitats with reduced oxygen. Understanding the regulation of horizontally transferred genes is important not only for microbial evolution but also for synthetic biology and the engineering of novel organisms, as these rely on the successful integration of foreign genes.
{"title":"Minimal transcriptional regulation of horizontally transferred photosynthesis genes in phototrophic bacterium <i>Gemmatimonas phototrophica</i>.","authors":"Karel Kopejtka, Jürgen Tomasch, Sahana Shivaramu, Mohit Kumar Saini, David Kaftan, Michal Koblížek","doi":"10.1128/msystems.00706-24","DOIUrl":"10.1128/msystems.00706-24","url":null,"abstract":"<p><p>The first phototrophic member of the bacterial phylum <i>Gemmatimonadota</i>, <i>Gemmatimonas phototrophica</i> AP64<sup>T</sup>, received all its photosynthesis genes via distant horizontal gene transfer from a purple bacterium. Here, we investigated how these acquired genes, which are tightly controlled by oxygen and light in the ancestor, are integrated into the regulatory system of its new host. <i>G. phototrophica</i> grew well under aerobic and semiaerobic conditions, with almost no difference in gene expression. Under aerobic conditions, the growth of <i>G. phototrophica</i> was optimal at 80 µmol photon m<sup>-2</sup> s<sup>-1</sup>, while higher light intensities had an inhibitory effect. The transcriptome showed only a minimal response to the dark-light shift at optimal light intensity, while the exposure to a higher light intensity (200 µmol photon m<sup>-2</sup> s<sup>-1</sup>) induced already stronger but still transient changes in gene expression. Interestingly, a singlet oxygen defense was not activated under any conditions tested. Our results indicate that <i>G. phototrophica</i> possesses neither the oxygen-dependent repression of photosynthesis genes known from purple bacteria nor the light-dependent repression described in aerobic anoxygenic phototrophs. Instead, <i>G. phototrophica</i> has evolved as a low-light species preferring reduced oxygen concentrations. Under these conditions, the bacterium can safely employ its photoheterotrophic metabolism without the need for complex regulatory mechanisms.</p><p><strong>Importance: </strong>Horizontal gene transfer is one of the main mechanisms by which bacteria acquire new genes. However, it represents only the first step as the transferred genes have also to be functionally and regulatory integrated into the recipient's cellular machinery. <i>Gemmatimonas phototrophica</i>, a member of bacterial phylum Gemmatimonadota, acquired its photosynthesis genes via distant horizontal gene transfer from a purple bacterium. Thus, it represents a unique natural experiment, in which the entire package of photosynthesis genes was transplanted into a distant host. We show that <i>G. phototrophica</i> lacks the regulation of photosynthesis gene expressions in response to oxygen concentration and light intensity that are common in purple bacteria. This restricts its growth to low-light habitats with reduced oxygen. Understanding the regulation of horizontally transferred genes is important not only for microbial evolution but also for synthetic biology and the engineering of novel organisms, as these rely on the successful integration of foreign genes.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0070624"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073320","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 : 2024-09-17Epub Date: 2024-08-21DOI: 10.1128/msystems.00422-24
Jack D Parsons, Clare R Cocker, Alison K East, Rachel M Wheatley, Vinoy K Ramachandran, Farnusch Kaschani, Markus Kaiser, Philip S Poole
Rhizobial attachment to host legume roots is the first physical interaction of bacteria and plants in symbiotic nitrogen fixation. The pH-dependent primary attachment of Rhizobium leguminosarum biovar viciae 3841 to Pisum sativum (pea) roots was investigated by genome-wide insertion sequencing, luminescence-based attachment assays, and proteomic analysis. Under acid, neutral, or alkaline pH, a total of 115 genes are needed for primary attachment under one or more environmental pH, with 22 genes required for all. These include components of cell surfaces and membranes, together with enzymes that construct and modify them. Mechanisms of dealing with stress also play a part; however, exact requirements vary depending on environmental pH. RNASeq showed that knocking out the two transcriptional regulators required for attachment causes massive changes in the bacterial cell surface. Approximately half of the 54 proteins required for attachment at pH 7.0 have a role in the later stages of nodule formation. We found no evidence for a single rhicadhesin responsible for alkaline attachment, although sonicated cell surface fractions inhibited root attachment at alkaline pH. Our results demonstrate the complexity of primary root attachment and illustrate the diversity of mechanisms involved.
Importance: The first step by which bacteria interact with plant roots is by attachment. In this study, we use a combination of insertion sequencing and biochemical analysis to determine how bacteria attach to pea roots and how this is influenced by pH. We identify several key adhesins, which are molecules that enable bacteria to stick to roots. This includes a novel filamentous hemagglutinin which is needed at all pHs for attachment. Overall, 115 proteins are required for attachment at one or more pHs.
{"title":"Factors governing attachment of <i>Rhizobium leguminosarum</i> to legume roots at acid, neutral, and alkaline pHs.","authors":"Jack D Parsons, Clare R Cocker, Alison K East, Rachel M Wheatley, Vinoy K Ramachandran, Farnusch Kaschani, Markus Kaiser, Philip S Poole","doi":"10.1128/msystems.00422-24","DOIUrl":"10.1128/msystems.00422-24","url":null,"abstract":"<p><p>Rhizobial attachment to host legume roots is the first physical interaction of bacteria and plants in symbiotic nitrogen fixation. The pH-dependent primary attachment of <i>Rhizobium leguminosarum</i> biovar viciae 3841 to <i>Pisum sativum</i> (pea) roots was investigated by genome-wide insertion sequencing, luminescence-based attachment assays, and proteomic analysis. Under acid, neutral, or alkaline pH, a total of 115 genes are needed for primary attachment under one or more environmental pH, with 22 genes required for all. These include components of cell surfaces and membranes, together with enzymes that construct and modify them. Mechanisms of dealing with stress also play a part; however, exact requirements vary depending on environmental pH. RNASeq showed that knocking out the two transcriptional regulators required for attachment causes massive changes in the bacterial cell surface. Approximately half of the 54 proteins required for attachment at pH 7.0 have a role in the later stages of nodule formation. We found no evidence for a single rhicadhesin responsible for alkaline attachment, although sonicated cell surface fractions inhibited root attachment at alkaline pH. Our results demonstrate the complexity of primary root attachment and illustrate the diversity of mechanisms involved.</p><p><strong>Importance: </strong>The first step by which bacteria interact with plant roots is by attachment. In this study, we use a combination of insertion sequencing and biochemical analysis to determine how bacteria attach to pea roots and how this is influenced by pH. We identify several key adhesins, which are molecules that enable bacteria to stick to roots. This includes a novel filamentous hemagglutinin which is needed at all pHs for attachment. Overall, 115 proteins are required for attachment at one or more pHs.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0042224"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018070","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 : 2024-09-17Epub Date: 2024-08-21DOI: 10.1128/msystems.00849-24
Dennis Tin Chat Chan, Hans C Bernstein
Engineering identical genetic circuits into different species typically results in large differences in performance due to the unique cellular environmental context of each host, a phenomenon known as the "chassis-effect" or "context-dependency". A better understanding of how genomic and physiological contexts underpin the chassis-effect will improve biodesign strategies across diverse microorganisms. Here, we combined a pangenomic-based gene expression analysis with quantitative measurements of performance from an engineered genetic inverter device to uncover how genome structure and function relate to the observed chassis-effect across six closely related Stutzerimonas hosts. Our results reveal that genome architecture underpins divergent responses between our chosen non-model bacterial hosts to the engineered device. Specifically, differential expression of the core genome, gene clusters shared between all hosts, was found to be the main source of significant concordance to the observed differential genetic device performance, whereas specialty genes from respective accessory genomes were not significant. A data-driven investigation revealed that genes involved in denitrification and components of trans-membrane transporter proteins were among the most differentially expressed gene clusters between hosts in response to the genetic device. Our results show that the chassis-effect can be traced along differences among the most conserved genome-encoded functions and that these differences create a unique biodesign space among closely related species.IMPORTANCEContemporary synthetic biology endeavors often default to a handful of model organisms to host their engineered systems. Model organisms such as Escherichia coli serve as attractive hosts due to their tractability but do not necessarily provide the ideal environment to optimize performance. As more novel microbes are domesticated for use as biotechnology platforms, synthetic biologists are urged to explore the chassis-design space to optimize their systems and deliver on the promises of synthetic biology. The consequences of the chassis-effect will therefore only become more relevant as the field of biodesign grows. In our work, we demonstrate that the performance of a genetic device is highly dependent on the host environment it operates within, promoting the notion that the chassis can be considered a design variable to tune circuit function. Importantly, our results unveil that the chassis-effect can be traced along similarities in genome architecture, specifically the shared core genome. Our study advocates for the exploration of the chassis-design space and is a step forward to empowering synthetic biologists with knowledge for more efficient exploration of the chassis-design space to enable the next generation of broad-host-range synthetic biology.
{"title":"Pangenomic landscapes shape performances of a synthetic genetic circuit across <i>Stutzerimonas</i> species.","authors":"Dennis Tin Chat Chan, Hans C Bernstein","doi":"10.1128/msystems.00849-24","DOIUrl":"10.1128/msystems.00849-24","url":null,"abstract":"<p><p>Engineering identical genetic circuits into different species typically results in large differences in performance due to the unique cellular environmental context of each host, a phenomenon known as the \"chassis-effect\" or \"context-dependency\". A better understanding of how genomic and physiological contexts underpin the chassis-effect will improve biodesign strategies across diverse microorganisms. Here, we combined a pangenomic-based gene expression analysis with quantitative measurements of performance from an engineered genetic inverter device to uncover how genome structure and function relate to the observed chassis-effect across six closely related <i>Stutzerimonas</i> hosts. Our results reveal that genome architecture underpins divergent responses between our chosen non-model bacterial hosts to the engineered device. Specifically, differential expression of the core genome, gene clusters shared between all hosts, was found to be the main source of significant concordance to the observed differential genetic device performance, whereas specialty genes from respective accessory genomes were not significant. A data-driven investigation revealed that genes involved in denitrification and components of trans-membrane transporter proteins were among the most differentially expressed gene clusters between hosts in response to the genetic device. Our results show that the chassis-effect can be traced along differences among the most conserved genome-encoded functions and that these differences create a unique biodesign space among closely related species.IMPORTANCEContemporary synthetic biology endeavors often default to a handful of model organisms to host their engineered systems. Model organisms such as <i>Escherichia coli</i> serve as attractive hosts due to their tractability but do not necessarily provide the ideal environment to optimize performance. As more novel microbes are domesticated for use as biotechnology platforms, synthetic biologists are urged to explore the chassis-design space to optimize their systems and deliver on the promises of synthetic biology. The consequences of the chassis-effect will therefore only become more relevant as the field of biodesign grows. In our work, we demonstrate that the performance of a genetic device is highly dependent on the host environment it operates within, promoting the notion that the chassis can be considered a design variable to tune circuit function. Importantly, our results unveil that the chassis-effect can be traced along similarities in genome architecture, specifically the shared core genome. Our study advocates for the exploration of the chassis-design space and is a step forward to empowering synthetic biologists with knowledge for more efficient exploration of the chassis-design space to enable the next generation of broad-host-range synthetic biology.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0084924"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018074","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 : 2024-09-17Epub Date: 2024-08-27DOI: 10.1128/msystems.00919-24
Tomás A Rush, Ann M Wymore, Miguel Rodríguez, Sara Jawdy, Rytas J Vilgalys, Madhavi Z Martin, Hunter B Andrews
Elemental profiling of fungal species as a phenotyping tool is an understudied topic and is typically performed to examine plant tissue or non-biological materials. Traditional analytical techniques such as inductively coupled plasma-optical emission spectroscopy (ICP-OES) and inductively coupled plasma-mass spectrometry (ICP-MS) have been used to identify elemental profiles of fungi; however, these techniques can be cumbersome due to the difficulty of preparing samples. Additionally, the instruments used for these techniques can be expensive to procure and operate. Laser-induced breakdown spectroscopy (LIBS) is an alternative elemental analytical technique-one that is sensitive across the periodic table, easy to use on various sample types, and is cost-effective in both procurement and operation. LIBS has not been used on axenic filamentous fungal isolates grown in substrate media. In this work, as a proof of concept, we used LIBS on two genetically distinct fungal species grown on a nutrient-rich and nutrient-poor substrate media to determine whether robust elemental profiles can be detected and whether differences between the fungal isolates can be identified. Our results demonstrate a distinct correlation between fungal species and their elemental profile, regardless of the substrate media, as the same strains shared a similar uptake of carbon, zinc, phosphorus, manganese, and magnesium, which could play a vital role in their survival and propagation. Independently, each fungal species exhibited a unique elemental profile. This work demonstrates a unique and valuable approach to rapidly phenotype fungi through optical spectroscopy, and this approach can be critical in understanding these fungi's behavior and interactions with the environment.
Importance: Historically, ionomics, the elemental profiling of an organism or materials, has been used to understand the elemental composition in waste materials to identify and recycle heavy metals or rare earth elements, identify the soil composition in space exploration on the moon or Mars, or understand human disorders or disease. To our knowledge, ionomic profiling of microbes, particularly fungi, has not been investigated to answer applied and fundamental biological questions. The reason is that current ionomic analytical techniques can be laborious in sample preparation, fail to measure all potential elements accurately, are cost-prohibitive, or provide inconsistent results across replications. In our previous efforts, we explored whether laser-induced breakdown spectroscopy (LIBS) could be used in determining the elemental profiles of poplar tissue, which was successful. In this proof-of-concept endeavor, we undertook a transdisciplinary effort between applied and fundamental mycology and elemental analytical techniques to address the biological question of how LIBS can used for fungi grown axenically in a nutrient-rich and nutrient-poor environment.
{"title":"Fungal elemental profiling unleashed through rapid laser-induced breakdown spectroscopy (LIBS).","authors":"Tomás A Rush, Ann M Wymore, Miguel Rodríguez, Sara Jawdy, Rytas J Vilgalys, Madhavi Z Martin, Hunter B Andrews","doi":"10.1128/msystems.00919-24","DOIUrl":"10.1128/msystems.00919-24","url":null,"abstract":"<p><p>Elemental profiling of fungal species as a phenotyping tool is an understudied topic and is typically performed to examine plant tissue or non-biological materials. Traditional analytical techniques such as inductively coupled plasma-optical emission spectroscopy (ICP-OES) and inductively coupled plasma-mass spectrometry (ICP-MS) have been used to identify elemental profiles of fungi; however, these techniques can be cumbersome due to the difficulty of preparing samples. Additionally, the instruments used for these techniques can be expensive to procure and operate. Laser-induced breakdown spectroscopy (LIBS) is an alternative elemental analytical technique-one that is sensitive across the periodic table, easy to use on various sample types, and is cost-effective in both procurement and operation. LIBS has not been used on axenic filamentous fungal isolates grown in substrate media. In this work, as a proof of concept, we used LIBS on two genetically distinct fungal species grown on a nutrient-rich and nutrient-poor substrate media to determine whether robust elemental profiles can be detected and whether differences between the fungal isolates can be identified. Our results demonstrate a distinct correlation between fungal species and their elemental profile, regardless of the substrate media, as the same strains shared a similar uptake of carbon, zinc, phosphorus, manganese, and magnesium, which could play a vital role in their survival and propagation. Independently, each fungal species exhibited a unique elemental profile. This work demonstrates a unique and valuable approach to rapidly phenotype fungi through optical spectroscopy, and this approach can be critical in understanding these fungi's behavior and interactions with the environment.</p><p><strong>Importance: </strong>Historically, ionomics, the elemental profiling of an organism or materials, has been used to understand the elemental composition in waste materials to identify and recycle heavy metals or rare earth elements, identify the soil composition in space exploration on the moon or Mars, or understand human disorders or disease. To our knowledge, ionomic profiling of microbes, particularly fungi, has not been investigated to answer applied and fundamental biological questions. The reason is that current ionomic analytical techniques can be laborious in sample preparation, fail to measure all potential elements accurately, are cost-prohibitive, or provide inconsistent results across replications. In our previous efforts, we explored whether laser-induced breakdown spectroscopy (LIBS) could be used in determining the elemental profiles of poplar tissue, which was successful. In this proof-of-concept endeavor, we undertook a transdisciplinary effort between applied and fundamental mycology and elemental analytical techniques to address the biological question of how LIBS can used for fungi grown axenically in a nutrient-rich and nutrient-poor environment.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0091924"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073269","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}