mSystems最新文献

{"title":"Jellyfish blooms-an overlooked hotspot and potential vector for the transmission of antimicrobial resistance in marine environments.","authors":"Alan X Elena, Neža Orel, Peiju Fang, Gerhard J Herndl, Thomas U Berendonk, Tinkara Tinta, Uli Klümper","doi":"10.1128/msystems.01012-24","DOIUrl":"10.1128/msystems.01012-24","url":null,"abstract":"<p><p>Gelatinous zooplankton (GZ) represents an important component of marine food webs, capable of generating massive blooms with severe environmental impact. When these blooms collapse, considerable amounts of organic matter (GZ-OM) either sink to the seafloor or can be introduced into the ocean's interior, promoting bacterial growth and providing a colonizable surface for microbial interactions. We hypothesized that GZ-OM is an overlooked marine hotspot for transmitting antimicrobial resistance genes (ARGs). To test this, we first re-analyzed metagenomes from two previous studies that experimentally evolved marine microbial communities in the presence and absence of OM from <i>Aurelia aurita</i> and <i>Mnemiopsis leidyi</i> recovered from bloom events and thereafter performed additional time-resolved GZ-OM degradation experiments to improve sample size and statistical power of our analysis. We analyzed these communities for composition, ARG, and mobile genetic element (MGE) content. Communities exposed to GZ-OM displayed up to fourfold increased relative ARG and up to 10-fold increased MGE abundance per 16S rRNA gene copy compared to the controls. This pattern was consistent across ARG and MGE classes and independent of the GZ species, indicating that nutrient influx and colonizable surfaces drive these changes. Potential ARG carriers included genera containing potential pathogens raising concerns of ARG transfer to pathogenic strains. <i>Vibrio</i> was pinpointed as a key player associated with elevated ARGs and MGEs. Whole-genome sequencing of a <i>Vibrio</i> isolate revealed the genetic capability for ARG mobilization and transfer. This study establishes the first link between two emerging issues of marine coastal zones, jellyfish blooms and ARG spread, both likely increasing with future ocean change. Hence, jellyfish blooms are a quintessential \"One Health\" issue where decreasing environmental health directly impacts human health.IMPORTANCEJellyfish blooms are, in the context of human health, often seen as mainly problematic for oceanic bathing. Here we demonstrate that they may also play a critical role as marine environmental hotspots for the transmission of antimicrobial resistance (AMR). This study employed (re-)analyses of microcosm experiments to investigate how particulate organic matter introduced to the ocean from collapsed jellyfish blooms, specifically <i>Aurelia aurita</i> and <i>Mnemiopsis leidyi</i>, can significantly increase the presence of antimicrobial resistance genes and mobile genetic elements in marine microbial communities by up to one order of magnitude. By providing abundant nutrients and surfaces for bacterial colonization, organic matter from these blooms enhances ARG proliferation, including transfer to and mobility in potentially pathogenic bacteria like <i>Vibrio</i>. Understanding this connection highlights the importance of monitoring jellyfish blooms as part of marine health assessments and developing strat","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0101224"},"PeriodicalIF":5.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399060","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}

{"title":"Integrating sequence composition information into microbial diversity analyses with k-mer frequency counting.","authors":"Nicholas A Bokulich","doi":"10.1128/msystems.01550-24","DOIUrl":"10.1128/msystems.01550-24","url":null,"abstract":"<p><p>k-mer frequency information in biological sequences is used for a wide range of applications, including taxonomy classification, sequence similarity estimation, and supervised learning. However, in spite of its widespread utility, k-mer counting has been largely neglected for diversity estimation. This work examines the application of k-mer counting for alpha and beta diversity as well as supervised classification from microbiome marker-gene sequencing data sets (16S rRNA gene and full-length fungal internal transcribed spacer [ITS] sequences). Results demonstrate a close correspondence with phylogenetically aware diversity metrics, and advantages for using k-mer-based metrics for measuring microbial biodiversity in microbiome sequencing surveys. k-mer counting appears to be a suitable and efficient strategy for feature processing prior to diversity estimation as well as supervised learning in microbiome surveys. This allows the incorporation of subsequence-level information into diversity estimation without the computational cost of pairwise sequence alignment. k-mer counting is proposed as a complementary approach for feature processing prior to diversity estimation and supervised learning analyses, enabling large-scale reference-free profiling of microbiomes in biogeography, ecology, and biomedical data. A method for k-mer counting from marker-gene sequence data is implemented in the QIIME 2 plugin q2-kmerizer (https://github.com/bokulich-lab/q2-kmerizer).</p><p><strong>Importance: </strong>k-mers are all of the subsequences of length k that comprise a sequence. Comparing the frequency of k-mers in DNA sequences yields valuable information about the composition of these sequences and their similarity. This work demonstrates that k-mer frequencies from marker-gene sequence surveys can be used to inform diversity estimates and machine learning predictions that incorporate sequence composition information. Alpha and beta diversity estimates based on k-mer frequencies closely correspond to phylogenetically aware diversity metrics, suggesting that k-mer-based diversity estimates are useful proxy measurements especially when reliable phylogenies are not available, as is often the case for some DNA sequence targets such as for internal transcribed spacer sequences.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0155024"},"PeriodicalIF":5.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458633","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}

{"title":"Long-read transcriptomics of caviid gammaherpesvirus 1: compiling a comprehensive RNA atlas.","authors":"Gábor Torma, Ákos Dörmő, Ádám Fülöp, Dóra Tombácz, Máté Mizik, Amanda M Pretory, See-Chi Lee, Zsolt Toth, Zsolt Boldogkői","doi":"10.1128/msystems.01678-24","DOIUrl":"10.1128/msystems.01678-24","url":null,"abstract":"<p><p>Caviid gammaherpesvirus 1 (CaGHV-1), formerly known as the guinea pig herpes-like virus, is an oncogenic gammaherpesvirus with a sequenced genome but an as-yet uncharacterized transcriptome. Using nanopore long-read RNA sequencing, we annotated the CaGHV-1 genome and constructed a detailed transcriptomic atlas. Our findings reveal diverse viral mRNAs and non-coding RNAs, along with mapped promoter elements for each viral gene. We demonstrated that the CaGHV-1 RTA lytic cycle transcription factor activates its own promoter, similar to Kaposi's sarcoma-associated herpesvirus (KSHV), and that the CaGHV-1 ORF50 promoter responds to RTA proteins from other gammaherpesviruses, highlighting the evolutionary conservation of RTA-mediated transcriptional mechanisms. Additionally, our analysis uncovered extensive transcriptional overlap within the viral genome, suggesting a role in regulating global gene expression. Given its tumorigenic properties, broad host range, and non-human pathogenicity, this work establishes CaGHV-1 as a promising small animal model for investigating human gammaherpesvirus pathogenesis.</p><p><strong>Importance: </strong>The molecular underpinnings of gammaherpesvirus pathogenesis remain poorly understood, partly due to limited animal models. This study provides the first comprehensive transcriptomic atlas of CaGHV-1, highlighting both coding and non-coding RNAs and revealing regulatory elements that drive viral gene expression. Functional studies of the CaGHV-1 RTA transcription factor demonstrated its ability to self-activate and cross-activate promoters from homologous gammaherpesviruses, reflecting conserved mechanisms of transcriptional control. These findings solidify CaGHV-1 as a unique and versatile small animal model, offering new opportunities to investigate gammaherpesvirus replication, transcriptional regulation, and tumorigenesis in a controlled experimental system.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0167824"},"PeriodicalIF":5.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516085","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}

{"title":"Identification and characterization of archaeal pseudomurein biosynthesis genes through pangenomics.","authors":"Valérian Lupo, Célyne Roomans, Edmée Royen, Loïc Ongena, Olivier Jacquemin, Coralie Mullender, Frédéric Kerff, Denis Baurain","doi":"10.1128/msystems.01401-24","DOIUrl":"10.1128/msystems.01401-24","url":null,"abstract":"<p><p>The peptidoglycan (PG, or murein) is a mesh-like structure, which is made of glycan polymers connected by short peptides and surrounds the cell membrane of nearly all bacterial species. In contrast, there is no PG counterpart that would be universally found in Archaea but rather various polymers that are specific to some lineages. Methanopyrales and Methanobacteriales are two orders of Euryarchaeota that harbor pseudomurein (PM), a structural analog of the bacterial PG. Owing to the differences between PG and PM biosynthesis, some have argued that the origin of both polymers is not connected. However, recent studies have revealed that the genomes of PM-containing Archaea encode homologs of the bacterial genes involved in PG biosynthesis, even though neither their specific functions nor the relationships within the corresponding inter-domain phylogenies have been investigated so far. In this work, we devised a pangenomic bioinformatic pipeline to identify proteins for PM biosynthesis in Archaea without prior genetic knowledge. The taxonomic distribution and evolutionary relationships of the candidate proteins were studied in detail in Archaea and Bacteria through HMM sequence mining and phylogenetic inference of the Mur domain-containing family, the ATP-grasp superfamily, and the MraY-like family. Our results show that archaeal muramyl ligases are of bacterial origin but diversified through a mixture of horizontal gene transfers and gene duplications. However, in the ATP-grasp and MraY-like families, the archaeal members were not found to originate from Bacteria. Our pangenomic approach further identified five new genes potentially involved in PM synthesis and that would deserve functional characterization.IMPORTANCE<i>Methanobrevibacter smithii</i> is an archaea commonly found in the human gut, but its presence alongside pathogenic bacteria during infections has led some researchers to consider it as an opportunistic pathogen. Fortunately, endoisopeptidases isolated from phages, such as PeiW and PeiP, can cleave the cell walls of <i>M. smithii</i> and other pseudomurein-containing archaea. However, additional research is required to identify effective anti-archaeal agents to combat these opportunistic microorganisms. A better understanding of the pseudomurein cell wall and its biosynthesis is necessary to achieve this goal. Our study sheds light on the origin of cell wall structures in those microorganisms, showing that the archaeal muramyl ligases responsible for its formation have bacterial origins. This discovery challenges the conventional view of the cell-wall architecture in the last archaeal common ancestor and shows that the distinction between \"common origin\" and \"convergent evolution\" can be blurred in some cases.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0140124"},"PeriodicalIF":5.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399040","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}

{"title":"Erratum for Wintenberg et al., \"Global Transcriptional Response of <i>Escherichia coli</i> Exposed <i>In Situ</i> to Different Low-Dose Ionizing Radiation Sources\".","authors":"Molly Wintenberg, Lisa Manglass, Nicole E Martinez, Mark Blenner","doi":"10.1128/msystems.00159-25","DOIUrl":"10.1128/msystems.00159-25","url":null,"abstract":"","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0015925"},"PeriodicalIF":5.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399048","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}

{"title":"Induction of conidial traps in the nematode-trapping fungus <i>Drechslerella dactyloides</i> by soil microbes.","authors":"Ling Zhang, Tao Zhang, Yan-Rui Xu, Jia-Mei Sun, Xue-Rong Pan, Kun-Ze Gu, Ke-Qin Zhang, Zhi-Gang Zhang, Lian-Ming Liang","doi":"10.1128/msystems.01291-24","DOIUrl":"10.1128/msystems.01291-24","url":null,"abstract":"<p><p>Nematode-trapping fungi, renowned for their specialized predatory structures that ensnare nematodes, offer a promising biological approach to managing plant-parasitic nematodes. However, the efficacy of these fungi is frequently hampered by biotic and abiotic factors within the soil, which can significantly impede fungal germination (fungistasis). To counteract these environmental challenges, certain nematode-trapping fungi have evolved to produce traps from their conidia, referred to as conidial traps. This adaptation allows them to bypass the inhibitory effects of their surroundings, enhancing their predatory capabilities. In this study, we explored how soil affects conidial trap formation in <i>Drechslerella dactyloides</i>. Our findings revealed that <i>Acinetobacter</i> spp. and <i>Pantoea</i> spp. present in soil extracts play pivotal roles in triggering the development of these traps. Using metagenomic sequencing, we mapped the shifts in bacterial communities and their relative abundances before and after incubation for up to 24 hours to optimize soil induction effects. This analysis highlighted the enrichment of specific functional genes in soil microbes and provided insights into the mechanisms driving conidial trap formation, based on changes in soil characteristics. Furthermore, through bacterial isolation procedures, we successfully cultured and characterized the bacteria responsible for this phenomenon, confirming their potent ability to stimulate the production of conidial traps in nematode-trapping fungi. This study not only underscores the critical role of bacterial diversity in modulating the life cycle transitions of nematode-trapping fungi but also sets the stage for the development of more effective and sustainable strategies to harness these fungi in the battle against pathogenic nematodes.</p><p><strong>Importance: </strong>Predatory nematode-trapping fungi are important microbial antagonists of nematodes and can be developed into biocontrol agents. However, microbial biocontrol agents often suffer from inconsistent efficacy, primarily due to biotic and abiotic stresses in the rhizosphere soil. <i>Drechslerella dactyloides</i>, a nematode-trapping fungus, produces conidial traps in soil, serving as a survival strategy to overcome these stresses. In this study, we optimized soil suspensions to efficiently induce the formation of conidial traps. We found that bacteria in the soil directly trigger this formation. Metagenomic sequencing revealed bacterial enrichment during optimization, and we isolated and purified these bacteria with inducible activity. Our research deepens the understanding of this survival strategy of nematode-trapping fungi in nature, laying the foundation for enhancing the effectiveness of nematode biocontrol using this mechanism.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0129124"},"PeriodicalIF":5.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408964","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}

{"title":"Correction for Taylor et al., \"Depression in Individuals Coinfected with HIV and HCV Is Associated with Systematic Differences in the Gut Microbiome and Metabolome\".","authors":"Bryn C Taylor, Kelly C Weldon, Ronald J Ellis, Donald Franklin, Tobin Groth, Emily C Gentry, Anupriya Tripathi, Daniel McDonald, Gregory Humphrey, MacKenzie Bryant, Julia Toronczak, Tara Schwartz, Michelli F Oliveira, Robert Heaton, Igor Grant, Sara Gianella, Scott Letendre, Austin Swafford, Pieter C Dorrestein, Rob Knight","doi":"10.1128/msystems.01305-24","DOIUrl":"10.1128/msystems.01305-24","url":null,"abstract":"","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0130524"},"PeriodicalIF":5.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080613","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}

{"title":"Rationally minimizing natural product libraries using mass spectrometry.","authors":"Monica Ness, Thilini Peramuna, Karen L Wendt, Jennifer E Collins, Jarrod B King, Raphaella Paes, Natalia Mojica Santos, Crystal Okeke, Cameron R Miller, Debopam Chakrabarti, Robert H Cichewicz, Laura-Isobel McCall","doi":"10.1128/msystems.00844-24","DOIUrl":"10.1128/msystems.00844-24","url":null,"abstract":"<p><p>Natural products are a critical source of novel chemotypes for drug discovery. However, the implementation of natural product extract libraries in high throughput screening is hampered by natural product structural redundancy and potential for bioactive re-discovery. This challenge and large library sizes drastically increase the time and cost during initial high throughput screens. To address these limitations, we developed a method that leverages liquid chromatography-tandem mass spectrometry spectral similarity to dramatically reduce natural product library size, with minimal bioactive loss, and applied this to a collection of fungal extracts. Importantly, this method also afforded increased bioassay hit rates against microbial targets, with broad applicability across assays and natural product sources. Thus, this method offers a broadly applicable strategy for accelerated and cost-effective natural product drug discovery.</p><p><strong>Importance: </strong>Natural product libraries are large collections of extracts derived from fungi, plants, bacteria, or any other natural sources. These libraries play an important role in the initial phases of drug discovery, providing the basis for bioassays against a target of interest. However, these collections often comprise thousands of extracts with sometimes overlapping chemical structures, which can result in a bottleneck in both time and costs for the initial phases of drug discovery. Here, we have developed a method that uses mass spectrometry to dramatically reduce the size of these libraries, with minimal tradeoffs and improved success rates in bioassays. Ultimately, this will speed up the process of bioactive candidate identification and isolation, and drug development overall.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0084424"},"PeriodicalIF":5.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483672","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}

{"title":"Environmental matrix and moisture influence soil microbial phenotypes in a simplified porous media incubation.","authors":"Josué Rodríguez-Ramos, Natalie Sadler, Elias K Zegeye, Yuliya Farris, Samuel Purvine, Sneha Couvillion, William C Nelson, Kirsten S Hofmockel","doi":"10.1128/msystems.01616-24","DOIUrl":"10.1128/msystems.01616-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Soil moisture and porosity regulate microbial metabolism by influencing factors, such as system chemistry, substrate availability, and soil connectivity. However, accurately representing the soil environment and establishing a tractable microbial community that limits confounding variables is difficult. Here, we use a reduced-complexity microbial consortium grown in a glass bead porous media amended with chitin to test the effects of moisture and a structural matrix on microbial phenotypes. Leveraging metagenomes, metatranscriptomes, metaproteomes, and metabolomes, we saw that our porous media system significantly altered microbial phenotypes compared with the liquid incubations, denoting the importance of incorporating pores and surfaces for understanding microbial phenotypes in soils. These phenotypic shifts were mainly driven by differences in expression of &lt;i&gt;Streptomyces&lt;/i&gt; and &lt;i&gt;Ensifer&lt;/i&gt;, which included a significant decrease in overall chitin degradation between porous media and liquid. Our findings suggest that the success of &lt;i&gt;Ensifer&lt;/i&gt; in porous media is likely related to its ability to repurpose carbon via the glyoxylate shunt amidst a lack of chitin degradation byproducts while potentially using polyhydroxyalkanoate granules as a C source. We also identified traits expressed by &lt;i&gt;Ensifer&lt;/i&gt; and others, including motility, stress resistance, and carbon conservation, that likely influence the metabolic profiles observed across treatments. Together, these results demonstrate that porous media incubations promote structure-induced microbial phenotypes and are likely a better proxy for soil conditions than liquid culture systems. Furthermore, they emphasize that microbial phenotypes encompass not only the multi-enzyme pathways involved in metabolism but also include the complex interactions with the environment and other community members.IMPORTANCESoil moisture and porosity are critical in shaping microbial metabolism. However, accurately representing the soil environment in tractable laboratory experiments remains a challenging frontier. Through our reduced complexity microbial consortium experiment in porous media, we reveal that predicting microbial metabolism from gene-based pathways alone often falls short of capturing the intricate phenotypes driven by cellular interactions. Our findings highlight that porosity and moisture significantly affect chitin decomposition, with environmental matrix (i.e., glass beads) shifting community metabolism towards stress tolerance, reduced resource acquisition, and increased carbon conservation, ultimately invoking unique microbial strategies not evident in liquid cultures. Moreover, we find evidence that changes in moisture relate to community shifts regarding motility, transporters, and biofilm formation, which likely influence chitin degradation. Ultimately, our incubations showcase how reduced complexity communities can be informative of microbial metabolism and present a useful","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0161624"},"PeriodicalIF":5.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483669","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}

{"title":"Association of tumor microbiome with survival in resected early-stage PDAC.","authors":"Yixuan Meng, Chan Wang, Mykhaylo Usyk, Soyoung Kwak, Chengwei Peng, Kenneth S Hu, Paul E Oberstein, Michelle Krogsgaard, Huilin Li, Richard B Hayes, Jiyoung Ahn","doi":"10.1128/msystems.01229-24","DOIUrl":"10.1128/msystems.01229-24","url":null,"abstract":"<p><p>The pancreas tumor microbiota may influence tumor microenvironment and influence survival in early-stage pancreatic ductal adenocarcinoma (PDAC); however, current studies are limited and small. We investigated the relationship of tumor microbiota to survival in 201 surgically resected patients with localized PDAC (Stages I-II), from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts. We characterized the tumor microbiome using RNA-sequencing data. We examined the association of the tumor microbiome with overall survival (OS), via meta-analysis with the Cox PH model. A microbial risk score (MRS) was calculated from the OS-associated microbiota. We further explored whether the OS-associated microbiota is related to host tumor immune infiltration. PDAC tumor microbiome α- and β-diversities were not associated with OS; however, 11 bacterial species, including species of <i>Gammaproteobacteria</i>, confirmed by extensive resampling, were significantly associated with OS (all <i>Q</i> < 0.05). The MRS summarizing these bacteria was related to a threefold change in OS (hazard ratio = 2.96 per standard deviation change in the MRS, 95% confidence interval = 2.26-3.86). This result was consistent across the two cohorts and in stratified analyses by adjuvant therapy (chemotherapy/radiation). Identified microbiota and the MRS also exhibited association with memory B cells and naïve CD4⁺ T cells, which may be related to the immune landscape through BCR and TCR signaling pathways. Our study shows that a unique tumor microbiome structure, potentially affecting the tumor immune microenvironment, is associated with poorer survival in resected early-stage PDAC. These findings suggest that microbial mechanisms may be involved in PDAC survival, potentially informing PDAC prognosis and guiding personalized treatment strategies.IMPORTANCEMuch of the available data on the PDAC tumor microbiome and survival are derived from relatively small and heterogeneous studies, including those involving patients with advanced stages of pancreatic cancer. There is a critical knowledge gap in terms of the tumor microbiome and survival in early-stage patients treated by surgical resection; we expect that advancements in survival may initially be best achieved in these patients who are treated with curative intent.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0122924"},"PeriodicalIF":5.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515963","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}