mSystems最新文献

{"title":"Large-scale genomic analysis places Chinese CC398 as a persistent human-associated MSSA lineage apart from the dominant global LA-MRSA clade.","authors":"Guilai Jiang, Changyuan Guo, Yulin Hua, Chaoshen Wu, Shengkai Li, Yuezhuo Wang, Jun Zhao, Linli Ji, Yijie Cheng, Zhemin Zhou, Xuejie Wu, Heng Li","doi":"10.1128/msystems.00621-26","DOIUrl":"10.1128/msystems.00621-26","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> clonal complex (CC)398 has emerged as a dominant livestock-associated methicillin-resistant <i>S. aureus</i> (LA-MRSA) lineage worldwide; however, its evolutionary trajectory and regional diversification remain incompletely understood. We developed a core-genome multilocus sequence typing (cgMLST) scheme with hierarchical clustering and applied it to over 30,000 <i>S. aureus</i> genomes, revealing frequent cross-border transmission of CC398. Subsequent time-calibrated phylogenetic analysis placed the most recent common ancestor at 1942 (95% CI: 1939-1945), with the human-to-livestock host jump around 1969 (95% CI: 1968-1972). Chinese CC398 exhibits a distinct trajectory: unlike the LA-MRSA lineages dominating Europe and North America, Chinese isolates are predominantly human-associated methicillin-susceptible <i>S. aureus</i> (HA-MSSA), forming unique East Asia-specific phylogroups (SAP1, SAP2, and AP1-AP3), with distinct resistance and virulence profiles. The LA lineage remains limited in China, with multinational mixed clusters emerging only after 2019. Analysis of global transmission networks revealed a significant correlation between LA-CC398 spread and international trade in fresh swine products, while no such correlation was observed for the human-associated lineage. Beyond the established lineage markers <i>tet</i>(M) and <i>scn</i>, our analysis identified additional differentially distributed genes, including <i>cadC</i>-a chromosomal cadmium resistance regulator-as a novel HA-lineage-enriched gene whose functional role in host adaptation remains to be determined. This study reveals that CC398 followed fundamentally different evolutionary paths in China versus Western countries, challenging a one-size-fits-all model of its dissemination.IMPORTANCEThis study illustrates how large-scale microbial genomics can resolve the evolutionary origins and regional diversification of bacterial pathogens. By applying a novel cgMLST scheme to over 30,000 <i>S. aureus</i> genomes, we show that CC398 followed fundamentally different evolutionary paths in China versus Western countries-challenging the prevailing model of uniform global dissemination-and that livestock-associated MRSA expansion is closely linked to international trade in fresh pork products. These findings highlight the need for integrated surveillance across human, animal, and trade interfaces to anticipate the emergence and spread of zoonotic pathogens.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0062126"},"PeriodicalIF":5.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944547","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":"A novel human <i>Streptomyces</i> strain redresses malignancy by inducing apoptosis and regaining gut homeostasis.","authors":"Yu-Hui Wang, Bao-Juan Yuan, Yao Meng, Hong-Tao Xu, Xin-Yu Gao, Liang Liu, Hong-Da Tian, Xiaoyu Wang, Xing-Hua Zhang, Song-Ling Zhu, Randal N Johnston, Le Tang, Gui-Rong Liu, Shu-Lin Liu","doi":"10.1128/msystems.00528-26","DOIUrl":"10.1128/msystems.00528-26","url":null,"abstract":"<p><p>Colorectal cancer is among the deadliest malignancies globally. The modern therapies do not lead to ideal outcomes due mostly to drug resistance and recurrence. Previously, we treated cancer patients by ameliorating the gut microbiome and achieved curative effects. We hypothesize that anticancer bacteria might be ubiquitous in the gut but suppressed under certain conditions, pointing to a possibility that an ameliorated gut ecology may help regain the abundance or functions of the hypothetical anticancer bacteria. Here, we show our successful isolation and polyphasic characterization of a gut bacterial strain, CGMCC 17111, which exhibited potent suppressive effects on colorectal cancer. CGMCC 17111 belongs to <i>Streptomyces</i> and is most closely related to the type strain of <i>Streptomyces albidoflavus</i>, DSM 40455^T. However, DSM 40455^T does not show any appreciable anticancer effects. Genetic, phenotypic, and functional analyses established CGMCC 17111 as representing a novel gut bacterial species with peculiar activities to redress malignancy without eliciting violent inflammatory reactions in the host.</p><p><strong>Importance: </strong>The human gut bacterial strain <i>Streptomyces</i> sp. CGMCC 17111 represents a genetically distinct gut-derived <i>Streptomyces</i> lineage that exhibited antitumor activity in both <i>in vitro</i> and <i>in vivo</i> experimental models. As a resident member of the human gut microbiota, CGMCC 17111 may contribute to host-microbiota interactions that influence tumor-associated biological processes. The findings of this study provide a foundation for future research into gut-derived microbial products and their potential applications in cancer therapy while preserving host physiological homeostasis.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0052826"},"PeriodicalIF":5.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025458","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":"Parasite-associated microbiomes in <i>Ascaris</i> and <i>Trichuris</i> nematodes: current evidence, challenges, and future directions.","authors":"Shezryna Shahrizal, Mohd Shafiq Aazmi, Yvonne Ai Lian Lim, Azdayanti Muslim","doi":"10.1128/msystems.00569-26","DOIUrl":"10.1128/msystems.00569-26","url":null,"abstract":"<p><p>Soil-transmitted helminth (STH) parasites, particularly <i>Ascaris lumbricoides</i> and <i>Trichuris trichiura</i>, co-exist and co-evolve with a complex human microbiota within the gut ecosystem. Most research has focused on how parasitic nematodes affect the host gut microbial structure and its consequences. In contrast, studies on the parasites' own associated microbiota remain underexplored. Understanding this gap is crucial, as it adds another layer of complexity to holobiont-holobiont interactions. Driven by the Parasite Microbiome Project, this review summarizes current evidence on <i>Ascaris-</i> and <i>Trichuris</i>-associated microbiomes from both natural and experimental studies, with a focus on their compositions, potential functional roles, challenges, and future directions. Existing findings are largely based on microbiomes associated with the gut of the parasites and are often characterized by transient, host-derived communities acquired through horizontal transmission, which may contribute to parasite survival and host interaction. We therefore emphasize the need to expand investigations to other specific tissues, particularly reproductive organs, as potential sites of a stable and conserved microbiota in STH parasites. Understanding this aspect is essential for advancing our knowledge of parasite-microbiome-host interactions in STH infections and may uncover the potential of microbiome-based therapeutic interventions for STH control and prevention.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0056926"},"PeriodicalIF":5.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025468","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":"Glutathione acts as an exometabolite that promotes growth recovery in fission yeast with defects in amino acid metabolism and cell polarity.","authors":"Ryotaro Yoshizumi, Shunichi Miura, Hiroaki Matoba, Go Hirai, Shumpei Asamizu, Hiroyasu Onaka, Yoko Yashiroda, Akihisa Matsuyama, Minoru Yoshida, Shinichi Nishimura","doi":"10.1128/msystems.00123-26","DOIUrl":"10.1128/msystems.00123-26","url":null,"abstract":"<p><p>Microorganisms in nature form communities through diverse interactions, such as mutualism and competition, to adapt to their ecological environments. These interactions seem to be mediated by extracellular metabolites (exometabolites), yet the chemical and biological diversity underlying these processes remains largely unexplored. In this study, we examined the chemical basis of exometabolite-mediated interactions in the fission yeast <i>Schizosaccharomyces pombe</i> by a genome-wide screen employing 3,420 viable gene deletion mutants. We identified 37 strains that exhibited growth defects in monoculture on a minimal medium but exhibited growth recovery in the vicinity of wild-type colonies (co-culture), suggesting that exometabolites derived from wild-type cells compensated for the gene deletion. Both lipophilic and water-soluble fractions obtained by solvent partitioning of the wild-type culture supernatant promoted growth recovery. Among the 11 mutants rescued by the water-soluble fraction, 6 were cysteine auxotrophs, prompting analyses of thiol-containing metabolites by liquid chromatography-mass spectrometry (LC-MS), revealing the presence of glutathione (GSH) in the culture supernatant. GSH restored growth in most strains as a nutrient source. In contrast, GSH rescued cell morphology defects in the <i>hob3</i>∆ mutant, lacking the Bin/amphiphysin/Rvs (BAR) adaptor protein Hob3, through a mechanism independent of nutrition. This research advances understanding of exometabolite-mediated interactions in <i>S. pombe</i> by identifying GSH as an exometabolite that influences cellular processes and potentially shapes microbial communities.</p><p><strong>Importance: </strong>Microorganisms secrete a wide range of metabolites that control microbial community behavior. These extracellular metabolites (exometabolites) include not only well-studied signaling molecules but also diverse primary and secondary metabolites, suggesting complex interactions among microbes. However, the molecular basis of these interactions remains poorly understood, partly due to challenges in detecting them experimentally. In this study, we surveyed exometabolites involved in cell-cell interactions in the model eukaryotic microorganism <i>Schizosaccharomyces pombe</i>. <i>S. pombe</i> releases a wide variety of metabolites outside the cells, including previously reported nitrogen signaling factors (NSFs) and glutathione (GSH) identified in this work. By analyzing gene deletion mutants whose growth is supported by extracellular GSH, we provide new insights into how secreted primary exometabolites compensate for specific genetic defects and influence cell physiology in microbial populations.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0012326"},"PeriodicalIF":5.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963655","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":"Prophage and metabolic determinants of <i>Staphylococcus aureus</i> survival to vancomycin identified via TraDIS screening.","authors":"Sophia Zborowsky, Urszula Łapińska, Paul A O'Neill, Audrey Farbos, Aaron R Jeffries, Xiaoliang Ba, Mark A Holmes, Maisem Laabei, Bing Zhang, Mark A T Blaskovich, Andrew Grant, Stefano Pagliara","doi":"10.1128/msystems.00734-26","DOIUrl":"10.1128/msystems.00734-26","url":null,"abstract":"<p><p>Reduced vancomycin susceptibility phenotypes in <i>Staphylococcus aureus</i> contribute to treatment failure, yet the genetic determinants of survival under inhibitory vancomycin exposure remain incompletely defined. We performed transposon-directed insertion-site sequencing (TraDIS) on a methicillin-resistant <i>S. aureus</i> (MRSA) ST398 mutant library following exposure to vancomycin at its minimum inhibitory concentration, identifying 52 genes whose disruption was associated with loss of population survival at inhibitory drug concentrations. Prophage-associated loci were the largest functional group, spanning predicted structural and regulatory genes, as well as multiple conserved hypothetical proteins. Targeted testing of defined transposon mutants in a USA300 background confirmed that disruption of selected loci impaired growth under vancomycin exposure. Our results highlight the contribution of diverse physiological processes, including metabolism and stress responses, as well as a prominent role for prophage-associated functions, rather than discrete resistance pathways. Together, these findings indicate that vancomycin tolerance is shaped by the general physiological state of the bacterial cell, including metabolic capacity and stress adaptation.IMPORTANCETreatment failure in <i>Staphylococcus aureus</i> infections often occurs in the absence of known antibiotic resistance determinants, suggesting that additional survival mechanisms influence therapeutic outcomes. In this study, we identify genetic determinants required for survival during inhibitory vancomycin exposure, revealing a broad role for metabolic functions, stress adaptation, and prophage-associated loci. The prominence of these diverse processes highlights that survival reflects global physiological adaptation rather than discrete resistance pathways. This insight underscores the need to consider cellular physiology and stress responses when developing strategies to prevent antibiotic tolerance and improve treatment efficacy.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0073426"},"PeriodicalIF":5.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977266","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":"A duty to act.","authors":"Emily Sickbert-Bennett, Philip J Rosenthal, Cesar A Arias, Gonzalo M Bearman, Paul E Sax, Graeme Forrest, David P Calfee, Romney M Humphries, Stanley Maloy, Ravi Jhaveri, Ira Blader, Ashley Shade, Roger Bedimo, Cynthia L Sears, Paul Katz, Barbara Resnick","doi":"10.1128/msystems.01094-26","DOIUrl":"10.1128/msystems.01094-26","url":null,"abstract":"","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0109426"},"PeriodicalIF":5.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944032","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":"Deciphering temporal antifungal dynamics of a rare actinomycete via integrated omics.","authors":"Hildah Amutuhaire, Michael Dubovis, Ivan Plyushchenko, Judith Kraut-Cohen, Tal Luzzatto-Knaan, Jonathan Friedman, Eddie Cytryn","doi":"10.1128/msystems.00694-26","DOIUrl":"10.1128/msystems.00694-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Fungal phytopathogens pose a persistent threat to global crop production, and widespread use of fungicides has driven resistance development and environmental concerns, necessitating sustainable alternatives. Actinomycetes produce diverse bioactive metabolites, yet natural product discovery has disproportionately focused on &lt;i&gt;Streptomyces&lt;/i&gt;, leaving rare actinomycete taxa underexplored. &lt;i&gt;Saccharomonospora xinjiangensis&lt;/i&gt; XJ-54 is a rare actinomycete exhibiting antifungal activity against Fusarium phytopathogens, including &lt;i&gt;Fusarium oxysporum&lt;/i&gt; f. sp&lt;i&gt;. cucumerinum&lt;/i&gt; (FORC), and harbors numerous biosynthetic gene clusters (BGCs) whose products remain uncharacterized. However, as in many rare actinomycetes, BGCs may be transcriptionally silent under standard laboratory conditions, and their expression dynamics remain poorly understood. To elucidate the molecular basis of antifungal activity in &lt;i&gt;S. xinjiangensis&lt;/i&gt; XJ-54, we integrated genomic, transcriptomic, and metabolomic analyses. Cell-free supernatants inhibited FORC after 5 days of fermentation, with activity increasing by day 7. Time-resolved RNA sequencing demonstrated that all genomically identified BGCs were transcriptionally active but exhibited distinct growth-phase-dependent expression patterns, with approximately half upregulated during exponential growth and the remainder following transition to stationary phase. We observed temporal variations in transcriptional coupling between cluster-specific regulators and biosynthetic genes. Liquid chromatography-mass spectrometry-based metabolomics showed growth-phase-dependent metabolite shifts, including stationary phase accumulation of secoiridoid-like monoterpenoids, N-acyl amines, and alkaloids (imidazoles, pyridines, and indoles), correlating with the observed antifungal phenotype. Bioactivity-guided fractionation subsequently yielded an active fraction containing a predicted halogenated alkaloid that induced hyphal damage in FORC. These findings indicate that antifungal activity in &lt;i&gt;S. xinjiangensis&lt;/i&gt; XJ-54 arises from temporally coordinated biosynthetic programs, providing a framework for optimizing growth conditions and prioritizing BGCs for functional characterization.IMPORTANCEThe discovery of new antifungal compounds is critical for sustainable agriculture, yet most natural product research has focused on a narrow range of well-studied microorganisms. Rare actinomycetes represent an untapped reservoir of chemical diversity, but their biosynthetic potential often remains hidden. By integrating time-resolved transcriptomics with metabolomics, we show that the rare actinomycete &lt;i&gt;Saccharomonospora xinjiangensis&lt;/i&gt; XJ-54 produces antifungal metabolites through temporally coordinated biosynthetic programs. Contrary to the prevailing assumption that the majority of biosynthetic gene clusters (BGCs) are silent, all BGCs in this strain showed detectable transcriptional activity under standard laboratory conditi","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0069426"},"PeriodicalIF":5.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069993","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":"Tryptophan-driven metabolomic shift in <i>Acidobacteriaceae</i> reveals phytohormones and antifungal metabolites.","authors":"Celine M Zumkeller, Christoph Hartwig, Walter Lanzalonga, Maria A Patras, Yang Liu, Michael Marner, Sanja Mihajlovic, Marius S Spohn, Till F Schäberle","doi":"10.1128/msystems.00828-26","DOIUrl":"10.1128/msystems.00828-26","url":null,"abstract":"<p><p><i>Acidobacteriota</i> is one of the most abundant phyla in soils and has recently attracted attention for its potential role in promoting phytosanitary benefits. The metabolomic capabilities of this phylum remain poorly characterized, with few experimentally confirmed metabolites described. To address these gaps, we combined untargeted metabolomic profiling with comparative genomic analyses to explore the functional potential of newly isolated <i>Acidobacteriaceae</i> strains. Genome mining across the <i>Acidobacteriota</i> phylum revealed the presence and taxon-specific enrichment of genes associated with plant-related traits, including phytohormone biosynthesis. In parallel, metabolomic analyses of OSMAC-derived extracts uncovered pronounced condition-dependent metabolic variation. Tryptophan supplementation was associated with marked metabolomic reprogramming, including changes in indole-derived metabolites, such as indole-3-acetic acid. Subsequent analyses linked these metabolic shifts to the suppression of phytopathogenic fungi and enabled the identification of malassezindoles and pityriacitrins as active compounds, confirmed by structure elucidation using NMR spectroscopy. Overall, these findings shed light on the previously unexplored metabolic potential of the <i>Acidobacteriota</i> phylum, emphasizing its ecological importance for phytosanitary applications.</p><p><strong>Importance: </strong>Despite their ubiquity and genomic diversity, the functional metabolism of members of the <i>Acidobacteriota</i> has largely remained uncharacterized. This study links genomic predictions to experimentally verified metabolomic outputs of <i>Acidobacteriaceae</i>, demonstrating tryptophan-responsive metabolic shifts translating to phytohormones and metabolites suppressing fungal growth. Our work underscores the emerging role of <i>Acidobacteriota</i> as important contributors to soil ecosystem functioning and plant-microbe interactions.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0082826"},"PeriodicalIF":5.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963572","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":"A robustness-first cross-disease framework supports a candidate shared microbial redox axis and disease-specific metabolic divergence in colorectal cancer, Crohn's disease, and liver cirrhosis.","authors":"Kartika Sahu, Palok Aich","doi":"10.1128/msystems.00836-26","DOIUrl":"10.1128/msystems.00836-26","url":null,"abstract":"<p><p>Gut microbiome dysbiosis is associated with colorectal cancer (CRC), Crohn's disease (CD), and liver cirrhosis (LC), yet whether these diseases share conserved microbial vulnerabilities remains unresolved. Analytical pipeline choices alone can shift apparent performance from near-zero to near-perfect on identical data, rendering cross-disease comparison unreliable. Here, in a secondary cross-sectional analysis of public data sets, maximin optimization is introduced as a proposed pipeline-selection criterion guaranteeing worst-case performance across all tasks simultaneously. Benchmarking 1,152 preprocessing-model configurations across six tasks using gut metagenomics and serum metabolomics from CRC, CD, and LC reveals a candidate 19-species microbiome signature in which <i>Firmicutes</i> bacterium CAG:41 is the sole threshold-stable cross-disease taxon, depleted in all three diseases. Microbiome pathway enrichment converges on sulfur-selenium redox metabolism and B-vitamin biosynthesis, while host metabolomic responses are predominantly disease-specific. CD and LC are dominated by single discriminative taxa; CRC requires community-level integration. Exploratory external evaluation was adequately powered only for CRC (AUC = 0.769, 95% bootstrap CI 0.678-0.849); CD and LC assessments were exploratory only.</p><p><strong>Importance: </strong>Cross-disease microbiome comparison has lacked a principled analytical foundation: arbitrary preprocessing choices can shift apparent classification performance from near-random to near-perfect on identical data, making biological conclusions unreliable when pooled across diseases. Maximin optimization addresses this by providing a decision-theoretic guarantee that every classification task contributes valid signal, enabling the first analytically controlled cross-disease comparison of gut metagenomics and serum metabolomics across three major gut-associated diseases. The identification of <i>Firmicutes</i> bacterium CAG:41 as the sole threshold-stable cross-disease taxon, harboring predicted functions in sulfur-selenium metabolism, offers a concrete target for experimental characterization and prospective screening validation. The two-layer dysbiosis architecture-universal microbial vulnerability with disease-specific host metabolic responses-provides a conceptual template for cross-disease microbiome study design in other gut-associated conditions, pending prospective confirmation.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0083626"},"PeriodicalIF":5.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963612","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":"Experimental benchmarking remains crucial to the interpretation of sequence annotation data.","authors":"Claire M Palmer","doi":"10.1128/msystems.00772-26","DOIUrl":"10.1128/msystems.00772-26","url":null,"abstract":"<p><p>Determining the distribution and origin of bacterial synthesis of metabolites of interest relies on computational prediction of protein function. In their recent study, Lawrence and colleagues employed a rigorous pipeline for benchmarking their annotation methods (E. C. Lawrence, H. Pan, N. Ollikainen, and B. J. Belin, mSystems 11:e00619-26, 2026, https://doi.org/10.1128/msystems.00619-26). This allowed them to distinguish between related yet functionally distinct proteins, thereby refining their understanding of bacterial hopanoid production. They find that the ability to synthesize these compounds likely arose in marine alphaproteobacteria and is related to osmotic stress tolerance. This study additionally provides new insights into the extracellular transport of hopanoids. The combination of large-scale computational analysis with experimentally based benchmarking that they describe provides a useful model for any researcher interested in understanding bacterial biosynthetic capability.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0077226"},"PeriodicalIF":5.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075311","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}