mSystems最新文献

{"title":"Clinical severity score-guided metagenomic analysis identifying gut microbial taxonomic and functional markers for severe hepatitis E progression.","authors":"Haiyan Shi, Yanfei Chen, Xiaoli Liu, Jiezuan Yang, Dong Yan, Hua Zhang, Jun Chen, Zhengjie Wu, Danying Yuan, Haifeng Lu, Lanjuan Li","doi":"10.1128/msystems.00956-26","DOIUrl":"10.1128/msystems.00956-26","url":null,"abstract":"<p><p>Although gut microbiome alterations have been reported in hepatitis E (HE), the taxonomic and functional determinants of disease severity remain poorly defined. Here, we performed shotgun metagenomic sequencing of fecal samples from 125 individuals spanning acute non-icteric hepatitis (ANIH), acute icteric hepatitis (AIH), acute liver failure (ALF), and healthy controls. We constructed a <b>s</b>urrogate clinical severity index from routine blood parameters and developed an integrative analytical framework that combined XGBoost-based taxonomic modeling with LASSO-driven functional feature selection to explore microbiome-severity associations. The taxonomic model discriminated patients from controls (area under the curve [AUC] = 0.944) and identified nine bacterial species significantly associated with severity, independent of age, sex, and body mass index (BMI) (permutation test, <i>P</i> < 0.05), with <i>Veillonella atypica</i> emerging as the most robust candidate biomarker. The signature featured enrichment of lactate-utilizing <i>Veillonella</i> spp. and <i>Ligilactobacillus salivarius</i>, alongside depletion of beneficial commensals (<i>Dorea longicatena</i>, <i>Ruminococcus timonensis</i>, <i>Eubacterium ramulus</i>), collectively suggesting a pathogenic \"lactate axis.\" The HE-enriched lactate utilizers were positively associated with 13 core severity-increasing KOs involved in oxidative stress adaptation (<i>npr</i>, <i>hemQ</i>, <i>NUDT1</i>, <i>nfr1</i>) and secretion/biofilm formation (<i>gspD</i>, <i>fhaC</i>, <i>vpr</i>, <i>sinR</i>) and negatively with three severity-decreasing KOs, including the butyrate fermentation gene (K14534). Strikingly, the stringent 16-KO core (intersection of four methods) explained more variance in disease severity than the broader set identified by at least three methods (<i>R</i>² = 0.61 vs. 0.47). Collectively, these findings reveal a strong link between microbiome-derived lactate metabolism and HE severity, highlighting its potential as a basis for microbiome-based severity stratification and motivating further mechanistic exploration.IMPORTANCEHepatitis E virus (HEV) infection ranges from ANIH to ALF, yet the role of the gut microbiome remains poorly understood across the severity spectrum. By performing shotgun metagenomic sequencing on fecal samples from 125 individuals and applying an integrative framework combining XGBoost-based taxonomic modeling with LASSO-driven functional selection, we identified robust microbiome-severity associations as quantified by a surrogate clinical severity index derived from routine blood parameters. These associations were characterized by enrichment of lactate-utilizing <i>Veillonella</i> species (notably <i>Veillonella atypica</i>), depletion of beneficial butyrate-producing commensals, and severity-linked shifts in microbial functional gene profiles. Such patterns are consistent with a perturbed microbial \"lactate axis\" in gut-liver crosstalk, although all ","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0095626"},"PeriodicalIF":5.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039757","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}

{"title":"Carbon source-dependent metabolic states govern redox homeostasis and cofactor biosynthesis in <i>Propionibacterium freudenreichii</i>.","authors":"Kirsi Savijoki, Bhawani Chamlagain, Minnamari Edelmann, Kaisa Hiippala, Paulina Deptula, Susanna Kariluoto, Tuula A Nyman, Vieno Piironen, Pekka Varmanen","doi":"10.1128/msystems.01023-26","DOIUrl":"10.1128/msystems.01023-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Microbial adaptation to fluctuating nutrient and oxygen conditions requires coordinated regulation of the metabolic network to maintain redox homeostasis within physicochemical and energetic constraints. While oxygen-dependent responses in &lt;i&gt;Propionibacterium freudenreichii&lt;/i&gt; (PFR) have been characterized at the transcriptomic level, the role of carbon source in defining system-level metabolic states remains unclear. Here, we investigated carbon source-dependent metabolic reprogramming and cofactor biosynthesis in PFR strain DSM 20271&lt;sup&gt;T&lt;/sup&gt; using label-free quantitative proteomics integrated with physiological and metabolite analyses. Distinct carbon sources defined discrete metabolic states shaped by redox constraints, carbon routing, and biosynthetic prioritization. Lactate supported a comparatively balanced physiological state characterized by enhanced respiratory metabolism, amino acid biosynthesis, and riboflavin metabolism, enabling high specific vitamin B12 yields (~100 µg g&lt;sup&gt;-1&lt;/sup&gt; wet biomass). In contrast, hexose metabolism (glucose and fructose) imposed a redox-constrained state marked by upregulation of transport systems, glycolysis, and the pentose phosphate pathway, resulting in increased biomass but reduced biosynthetic efficiency. A defining feature of the hexose-driven state was activation of aspartate metabolism. Proteomic and metabolite data, together with functional assays, support a model in which aspartate is converted to fumarate and subsequently reduced to succinate consistent with an alternative electron sink that could facilitate NADH reoxidation under redox-constrained conditions. Together, these findings establish that carbon source shapes physiological state through carbon routing, redox homeostasis, and differential resource allocation, with cofactor biosynthesis emerging as a system-level property rather than a simple consequence of biosynthetic enzyme abundance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;&lt;i&gt;Propionibacterium freudenreichii&lt;/i&gt; is used in food fermentations and is one of the few microorganisms able to synthesize biologically active vitamin B12, making it valuable for industry and biotechnology. Yet the metabolic principles governing its performance across growth conditions remain poorly understood. Here, we show that carbon source is a key determinant of metabolic state, dictating how cells resolve redox constraints and allocate biosynthetic resources. We identify an adaptation in sugar-grown cells in which aspartate metabolism provides a potential alternative electron sink to sustain redox balance under constrained conditions. By contrast, lactate supports a physiological state that promotes efficient vitamin B12 biosynthesis. These findings reveal a central role for carbon source in shaping metabolic configuration and identify redox balancing as a critical lever linking environmental inputs to biosynthetic output. This work provides mechanistic insight into redox-constrained metabolism","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0102326"},"PeriodicalIF":5.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070004","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}

{"title":"FNR/ArcA-2,3-butanediol regulatory axis enhances glucose uptake and <i>adhE</i> expression in high alcohol-producing <i>Klebsiella pneumoniae</i>.","authors":"Zheng Fan, Tongtong Fu, Yuchen Chen, Hongbo Liu, Zhoufei Li, Yufei Yin, Bing Du, Xiaohu Cui, Lin Gan, Guanhua Xue, Yanling Feng, Hanqing Zhao, Jinghua Cui, Chao Yan, Junxia Feng, Ziying Xu, Zihui Yu, Yang Yang, Yuehua Ke, Jing Yuan","doi":"10.1128/msystems.01007-26","DOIUrl":"https://doi.org/10.1128/msystems.01007-26","url":null,"abstract":"<p><p>Previously, we found that <i>Klebsiella pneumoniae</i> is a high-alcohol producer, which contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, the molecular mechanisms underlying its high-alcohol production remain unclear. By comparing biological phenotypes of <i>K. pneumoniae</i> with those of <i>Escherichia coli</i>, we found that the former is better at metabolizing high concentrations of glucose, exhibits faster growth rates, and produces higher levels of alcohol, with the 2,3-butanediol (2,3-BD) pathway being the key determinant underlying these differences. More importantly, species possessing the 2,3-BD pathway, including <i>Klebsiella aerogenes</i>, <i>Klebsiella oxytoca</i>, <i>Enterobacter cloacae</i>, and <i>Enterobacter hormaechei</i>, have all demonstrated high-alcohol production capabilities similar to that of <i>K. pneumoniae</i>, suggesting a conserved mechanism for alcohol production among 2,3-BD-positive <i>Enterobacteriaceae</i>. Deletion of the 2,3-BD pathway reduced the expression of the phosphotransferase system (PTS) and the alcohol dehydrogenase gene <i>adhE</i>, which normally confer enhanced glucose metabolism and alcohol production. Pathway deletion also downregulated multiple virulence determinants, including capsular polysaccharides (CPS), lipopolysaccharides (LPS), and type 1 and 3 fimbriae, thereby attenuating virulence in a murine pneumonia model. In addition, the regulator FNR enhanced alcohol production by upregulating <i>adhE</i> and 2,3-BD pathway genes, whereas ArcA activated the 2,3-BD pathway in an ArcB-independent manner, revealing a non-canonical signaling mechanism that couples metabolic adaptation with virulence. Collectively, our findings identify the \"FNR/ArcA-2,3-BD pathway axis\" as a key molecular mechanism driving high alcohol production in <i>K. pneumoniae</i>, highlighting the 2,3-BD pathway as a key link between bacterial metabolism and virulence and a potential therapeutic target for controlling <i>K. pneumoniae</i> infections.IMPORTANCE<i>Klebsiella pneumoniae</i> has emerged as a novel cause of NAFLD due to its high alcohol-producing capacity. However, the molecular basis of this phenotype remains unclear. In this study, we demonstrate that the FNR/ArcA-2,3-BD pathway axis drives high levels of alcohol production by enhancing glucose-PTS system and <i>adhE</i> expression, and that this pathway is conserved among <i>Enterobacteriaceae</i> with strong alcohol-producing abilities. Moreover, loss of the 2,3-BD pathway reduces the expression of multiple virulence factors and attenuates pathogenicity in a murine pneumonia model. These findings identify the FNR/ArcA-2,3-BD axis as a potential target for mitigating excessive alcohol production and virulence in bacteria.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0100726"},"PeriodicalIF":5.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195327","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}

{"title":"Dynamic nutrient competition (de-)stabilizes photosymbiosis.","authors":"Edvin Löthgren, Nils Rädecker, Ursula Gaedke, Toni Klauschies","doi":"10.1128/msystems.00631-26","DOIUrl":"https://doi.org/10.1128/msystems.00631-26","url":null,"abstract":"<p><p>Photosymbioses between heterotrophic hosts and phototrophic symbionts are critical to productivity in oligotrophic aquatic ecosystems. The ecological success of this relationship is rooted in the efficient metabolic exchange between symbiotic partners, yet this nutritional dependency may render these systems highly sensitive to anthropogenic changes. Recent studies suggest that competitive partitioning of nutrients between partners is critical for the maintenance and regulation of symbiotic interactions. However, a solid theoretical foundation for the nutritional regulation of photosymbioses is still lacking. Thus, we designed a mechanistic population model to investigate whether observed ecological dynamics of photosymbioses can be explained by competition for the same limiting nutrient within the holobiont. Our model gives rise to a bistable system where a disturbance in nutrient competition can shift the symbiosis from a \"symbiotic\" state of efficient carbon recycling between the two partners into a \"dysbiotic\" state where no photosynthates are allocated to the host. We show that environmental factors such as temperature and nutrient availability, as well as symbiont traits such as nutrient-assimilation rates, may affect the sensitivity of the system to such disturbances. Critically, this nutritional regulation results in a trade-off in which the traits that enhance the fitness of symbiotic partners under stable conditions also enhance their susceptibility to environmental change. The model results reveal that nutrient competition is sufficient to explain ecological dynamics of establishment and initial breakdown of the symbiosis, and provide key insights into an evolutionary trajectory that favors productivity over heat resistance.IMPORTANCEPhotosymbiosis, the partnership between heterotrophic hosts and phototrophic symbionts, is a cornerstone of evolutionary innovation that sustains biodiversity from tropical coral reefs to temperate lakes. Despite their evolutionary success, these associations are surprisingly susceptible to anthropogenic change. By developing a universal population growth model, we demonstrate that the very metabolic interactions that sustain their immense productivity also create an inherent sensitivity to anthropogenic stress. We show that the competition for essential nutrients within the partnership makes the most productive symbioses the most vulnerable to breakdown. This work provides a mechanistic framework to predict how global change threatens the stability of these vital ecological cornerstones, offering a new lens through which to understand and mitigate symbiotic collapse.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0063126"},"PeriodicalIF":5.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195358","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}

{"title":"MIMEco: multi-objective metabolic modeling to predict and explain pairwise interactions.","authors":"Anna Lambert, Samuel Chaffron, Damien Eveillard","doi":"10.1128/msystems.01195-26","DOIUrl":"https://doi.org/10.1128/msystems.01195-26","url":null,"abstract":"<p><p>Genome-scale metabolic models provide a mechanistic framework for quantitatively exploring an organism's physiology and its interactions with the environment. However, their use in microbial community modeling has been limited since it usually relies on community-wide objective functions or the integration of community abundance data. Nevertheless, predicting microbial interactions is crucial for understanding ecosystem dynamics and thus requires dedicated methods. Here, we introduce Metabolic Interaction Modeling in Ecosystems (MIMEco), an open-source Python package that predicts pairwise microbial interactions through multi-objective optimization. MIMEco does not require abundance data, provides a user-friendly workflow, and predicts interaction types, strengths, and exchanged metabolites directly from Pareto fronts. In this study, MIMEco is validated by replicating experimental results of an <i>in vitro</i> co-culture of two auxotrophic <i>Escherichia coli</i> strains. By combining mechanistic inference with usability, MIMEco makes metabolic interaction modeling accessible to non-specialists while remaining flexible for experts, establishing a versatile platform for advancing metabolic ecology across biomedical and environmental fields.</p><p><strong>Importance: </strong>Deciphering microbial interactions through <i>in vitro</i> experiments is often costly and limited in scope, while existing bioinformatics tools can be complex to use or limited by actual sample data. Metabolic Interaction Modeling in Ecosystem (MIMEco) offers an open-source and user-friendly multi-objective framework for predicting and quantifying pairwise microbial ecosystem interactions and nutrient exchanges. We demonstrate its reliability by replicating a well-characterized laboratory experiment, showing that MIMEco can accurately reflect real biological behavior. This tool improves the community's ability to explore and understand metabolic interaction mechanisms underpinning microbial ecosystems.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0119526"},"PeriodicalIF":5.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195332","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}

{"title":"Non-redundant cardiolipin synthase family proteins shape lipid composition and stress resilience in <i>Bacteroides fragilis</i>.","authors":"Matthew K Schnizlein, Bongjin Hong, Jennifer N T Nguyen, Katarina Jones, Alyssa I Rodriguez, Aretha Fiebig, Shawn R Campagna, Marcy J Balunas, Thomas V O'Halloran, Sean Crosson","doi":"10.1128/msystems.00749-26","DOIUrl":"10.1128/msystems.00749-26","url":null,"abstract":"<p><p>Gut-resident bacteria must withstand membrane-disrupting stresses, such as bile acids, to persist in the intestinal environment. The Bacteroidota are a dominant phylum of the human gut microbiota. However, the genes responsible for the synthesis of membrane lipids in this phylum remain relatively uncharacterized. <i>Bacteroides fragilis</i> is a prevalent member of this phylum and encodes two predicted cardiolipin synthase family proteins, ClsA and ClsB. We previously identified both <i>cls</i> genes as bile-acid fitness factors in <i>B. fragilis</i> P207, but the contributions of <i>clsA</i> and <i>clsB</i> to cell physiology remained unclear. Here, we combine targeted gene deletion with high-resolution lipidomics, metabolomics, and elemental mass spectrometry to show that ClsA and ClsB have distinct and non-redundant functions in the cell. Each <i>cls</i> gene differs in its growth-phase expression pattern, and deletion of each gene produces distinct effects on cell morphology, fitness under membrane-perturbing stress, and the broader metabolome. <i>clsA</i> and <i>clsB</i> strongly influence the levels of different glycyl-seryl peptidolipids, a <i>Bacteroides</i> lipid family that includes immune-active lipids, and whose loss impairs bile acid resistance and gut colonization. In contrast to the acute ion-gradient disruption caused by the secondary bile acid deoxycholate, deletion of <i>clsA</i> and <i>clsB</i> did not measurably alter steady-state intracellular ion levels under standard growth conditions. Together, these results define related but non-redundant roles for two cardiolipin synthase family proteins in a common member of the human gut microbiota.IMPORTANCEThe gut bacterium <i>Bacteroides fragilis</i> is a normal member of the human intestinal microbiota that can also bloom to high abundance in inflamed guts. To survive within the gut, <i>B. fragilis</i> must maintain the integrity and function of its cell membrane. In this study, we report that the two cardiolipin synthase family genes in the <i>B. fragilis</i> genome impact the cell's lipid profile in distinct ways and contribute differently to how <i>B. fragilis</i> responds to membrane stress. Our work provides insight into how a common gut bacterium adapts to conditions encountered in the intestine and improves understanding of membrane biology in this important group of gut microbes.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0074926"},"PeriodicalIF":5.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195325","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}

{"title":"Analysis of metabolic interactions in an artificial consortium including butyrogenic gut microbes.","authors":"Alexis Torres-Miranda, Giselle Guron, John Renye, Arland Hotchkiss, Daniel Garrido","doi":"10.1128/msystems.00612-26","DOIUrl":"https://doi.org/10.1128/msystems.00612-26","url":null,"abstract":"<p><p>Cross-feeding interactions shape gut microbial communities and contribute to the establishment of bacteria associated with beneficial fermentation products such as butyrate. However, many gut microbes involved in fiber degradation and butyrate-associated trophic networks remain poorly characterized. Here, we combined genomic analysis of candidate strains, genome-scale metabolic modeling, <i>in vitro</i> cultivation, and transcriptomics to investigate metabolic interactions among gut bacteria during growth on inulin. Genomic analyses identified genes associated with inulin utilization, fermentation enzymes, and amino acid synthesis and transport. <i>In vitro</i> screening of different bacterial combinations on inulin identified <i>Clostridium</i> sp. HGF2 as an inulin-degrading, butyrate-producing strain, leading us to focus on its interaction with <i>Bifidobacterium animalis</i> subsp. <i>lactis</i> PT33. Co-culture assays, transwell experiments, and batch bioreactor analyses supported metabolic interactions between both strains during growth on inulin. Although PT33 did not enhance butyrate production, the combined results were consistent with competition for readily available carbohydrates, while transcriptomics and model integration suggested that HGF2 degrades inulin and releases simple carbohydrates that can be utilized by PT33, while PT33 produces acetate and lactate that support HGF2 metabolism. Altogether, this work shows a methodology to identify and evaluate candidate cross-feeding interactions in artificial gut communities, in this case, revealing a competitive rather than synergistic interaction, and characterizes HGF2, identified here as <i>Clostridium innocuum</i>, as an understudied butyrate-producing, inulin-degrading strain.</p><p><strong>Importance: </strong>Understanding microbial and metabolic interactions that support butyrate producers is important for developing strategies to promote beneficial gut bacteria. However, most cross-feeding studies have focused on butyrate producers from the genera <i>Faecalibacterium</i>, <i>Eubacterium</i>, <i>Anaerostipes</i>, and <i>Roseburia</i>, leaving many other butyrate-producing bacteria poorly characterized. Here, we characterize the interaction between <i>Clostridium</i> sp. HGF2 and <i>Bifidobacterium animalis</i> subsp. <i>lactis</i> PT33 using RNA-seq and genome-scale metabolic modeling. Starting from a pool of candidate butyrate producers selected through genomic analysis and <i>in vitro</i> experiments, we identified HGF2 as a strain of interest and explored its metabolic interaction with PT33.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0061226"},"PeriodicalIF":5.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183026","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}

{"title":"Environmental gradients shape the hydrocarbon-degrading microbiome in two mid-Atlantic bays.","authors":"Dinuka L J Patabandige, Jojy John, Maximiliano Ortiz, Barbara J Campbell","doi":"10.1128/msystems.00866-26","DOIUrl":"10.1128/msystems.00866-26","url":null,"abstract":"<p><p>Hydrocarbons are recalcitrant organic matter that is released into the environment via natural and anthropogenic activities. We hypothesized that abiotic and biotic factors, including salinity, temperature, seasonality, microbial interactions, and functional redundancy, influence the abundance and activity of potential hydrocarbon degraders in the Delaware and Chesapeake Bays. We identified key genes in hydrocarbon degradation pathways in metagenomes, metatranscriptomes, and metagenome-assembled genomes (MAGs) from these estuaries. In the surface waters of both estuaries, aerobic aromatic and alkane degradation pathways predominated, with higher gene abundances observed in low-salinity spring and summer samples. Salinity significantly structured both hydrocarbon-degrading MAG abundances, alongside temperature, nitrate, and silicate concentrations, and hydrocarbon degradation gene expression, which additionally varied seasonally, with the highest relative expression of aromatic degradation genes in low-salinity samples. Catechol degradation pathways exhibited high functional redundancy, whereas the naphthalene degradation pathway showed restricted distribution. Co-expression analysis revealed that <i>Burkholderiales</i> displayed condition-dependent metabolic coupling, while <i>Pseudomonadales</i> integrated hydrocarbon degradation with fermentation and central metabolism, demonstrating complementary strategies that support multi-scale ecosystem resilience. Together, these results support our hypothesis that environmental gradients and taxon-specific metabolic strategies jointly structure the abundance and <i>in situ</i> activity of hydrocarbon degraders, with implications for predicting ecosystem responses to hydrocarbon inputs under changing conditions.</p><p><strong>Importance: </strong>Coastal estuaries are among the most contaminated aquatic environments on Earth, receiving continuous hydrocarbon inputs from industrial activity, urban runoff, and natural sources. Microorganisms are the primary agents of hydrocarbon breakdown in these systems, yet predicting when and where this capacity is active and how resilient it is to environmental change remains a major challenge. Using paired genomic and transcriptomic data from microbial genomes across two major mid-Atlantic estuaries, we show that hydrocarbon degradation capacity is not uniformly distributed but is instead shaped by salinity, nutrients, and seasonality in pathway-specific ways. Critically, dominant degrader taxa employ fundamentally different metabolic strategies to sustain this function across fluctuating conditions, providing a form of community-level insurance against environmental disturbance. These findings advance our ability to predict microbial hydrocarbon degradation in coastal systems and inform nature-based approaches to bioremediation under increasing climate and anthropogenic pressures.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0086626"},"PeriodicalIF":5.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183061","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}

{"title":"Acquisition of a toxin-antitoxin system within a mobile genetic element likely enhances <i>Mycobacterium abscessus</i> fitness by enforcing cargo retention.","authors":"Nikita H Amin, Eduardo A Troian, Heather M Maldonado, Nancy A Woychik","doi":"10.1128/msystems.00934-26","DOIUrl":"https://doi.org/10.1128/msystems.00934-26","url":null,"abstract":"<p><p>Infections caused by the emerging pathogen <i>Mycobacterium abscessus</i> (Mab) require prolonged multidrug treatment regimens that frequently fail because its accessory genome has incorporated a daunting array of poorly defined resistance mechanisms. However, the processes governing acquisition and retention of new genetic material within the Mab accessory genome remain poorly understood. Here, we first identified two Mab clinical strains that harbor the same uncharacterized toxin-antitoxin (TA) system at different genomic positions. Using computational analyses of the surrounding DNA context, we discovered that each TA system resides within identical mobile genetic element (MGE) cassettes whose positions exchange between the two strains via site-specific recombinases. We then applied a specialized 5' RNA-seq approach to identify initiator tRNA^fMet as the exclusive RNA target of the VapC2 TA toxin residing within the MGE. VapC2-mediated tRNA^fMet inactivation by cleavage at its anticodon stem loop leads to growth arrest and global translation inhibition. This activity ensures stable inheritance of the MGE and its resident cargo genes through a mechanism similar to postsegregational killing. Our findings uncover the mechanism for durable expansion of the Mab accessory genome and suggest a selective advantage whereby toxin-mediated entry into a reversible growth-arrested state may reduce antibiotic susceptibility. Together, these results illustrate how retention of horizontally acquired MGEs containing a potent TA system can drive adaptive genome evolution to enhance fitness in this highly drug-resistant pathogen.</p><p><strong>Importance: </strong><i>Mycobacterium abscessus</i> (Mab) causes chronic lung disease and skin and soft tissue infections, posing a major threat to individuals with cystic fibrosis, underlying lung disease, lung transplants, or weakened immune systems. Unlike <i>Mycobacterium tuberculosis</i>, Mab has a large and highly plastic accessory genome generally thought to be predominantly shaped by horizontal gene transfer and recombination. However, the mechanisms that stabilize newly acquired genetic material in this pathogen remain poorly understood. Here, we identify a toxin-antitoxin (TA) system embedded within a mobile genetic element (MGE) predicted to enforce stable retention of the MGE through a mechanism similar to postsegregational killing. The toxin inactivates initiator tRNA^fMet, inducing reversible growth arrest that likely reduces antibiotic efficacy. By functioning as an addiction module, this TA system also ensures stable inheritance of co-transferred accessory genes within the MGE, providing a mechanism for long-term retention of horizontally acquired genetic material that enhances pathogen fitness.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0093426"},"PeriodicalIF":5.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183101","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}

{"title":"Comparative transcriptional network analysis reveals ecological specialization in infant-associated species of <i>Bifidobacterium</i>.","authors":"Felipe Melis-Arcos, Masanori Arita, Daniel Garrido","doi":"10.1128/msystems.01082-26","DOIUrl":"https://doi.org/10.1128/msystems.01082-26","url":null,"abstract":"<p><p><i>Bifidobacterium</i> species are important microorganisms in the infant gut microbiota displaying substantial genomic diversity, yet how this variability is reflected in transcriptional regulatory architecture remains an open question. Here, we integrated pangenome analysis with transcription factor binding site inference and network-based approaches to compare regulatory architectures across <i>Bifidobacterium longum</i> subsp. <i>infantis</i>, <i>Bifidobacterium breve</i>, and <i>B. longum</i> subsp. <i>longum</i> using over 300 high-quality genomes. All three species exhibited open pangenomes, with regulatory interactions frequently involving accessory genes. Inferred network metrics were compared with score-randomized controls across motif-score thresholds. Increasing score stringency reduced network size while increasing the number of detected communities, indicating greater fragmentation of the retained networks rather than a measured increase in modularity. <i>NrdR</i> showed an intermediate overlap in the Clusters of Orthologous Groups (COG) category sets represented among its predicted targets and species-dependent target prevalence. HMO-related regulators (<i>FucR</i>, <i>NanR</i>, and <i>NagR</i>) differed descriptively between <i>Bifidobacterium infantis</i> and <i>B. breve</i>, the two species included in the complete three-regulator comparison, in predicted target counts, represented COG category sets, and genomic-prevalence patterns; only <i>FucR</i> showed a significant difference in accessory-target fraction. These findings identify species-dependent differences in predicted regulon composition and genomic prevalence and provide testable hypotheses about how regulatory architecture may relate to ecological specialization in the infant gut.</p><p><strong>Importance: </strong><i>Bifidobacterium</i> species are among the most abundant microorganisms in the breast-fed infant gut microbiota, where they display distinct patterns of genomic diversification and host association. However, the transcriptional regulatory mechanisms underlying these species-specific differences remain incompletely characterized. Here, we reconstructed and compared genome-scale transcriptional regulatory networks across three infant-associated <i>Bifidobacterium</i> species, integrating pangenome structure with transcription factor binding site inference across more than 300 genomes. Our analyses identified predicted regulatory interactions involving accessory genes and species-specific differences in network structure, regulon composition, and target prevalence. These associations provide hypotheses for experimental studies of how gene content and regulatory architecture may contribute to niche adaptation. This pangenome-scale framework can support the prioritization of regulatory hypotheses for future functional studies of infant-associated <i>Bifidobacterium</i>.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0108226"},"PeriodicalIF":5.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166740","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}