mSystems最新文献

{"title":"The gut remembers: the long-lasting effect of medication use on the gut microbiome.","authors":"Pamela Ferretti","doi":"10.1128/msystems.01076-25","DOIUrl":"https://doi.org/10.1128/msystems.01076-25","url":null,"abstract":"<p><p>Growing evidence suggests that antibiotics and many human-targeted medications can alter the gut microbiome composition, but the persistence of these effects remains unclear. In their article, Aasmets and colleagues (O. Aasmets, N. Taba, K. L. Krigu, R. Andreson, et al., mSystems e00541-25, 2025, https://doi.org/10.1128/msystems.00541-25) leveraged electronic health records (EHR) and stool metagenomic data from 2,509 individuals to assess the impact of past medication use (up to 5 years prior to sampling) on the gut microbiome composition. They found that nearly half of the 186 tested drugs had long-term effects, with antibiotics, beta-blockers, benzodiazepine derivatives, proton-pump inhibitors, and antidepressants associated with microbiome changes that persisted for years after intake. For some medications, the effects were additive, with greater impact observed after repeated use. Overall, the authors highlight how medication use in the years preceding sample collection represents an often overlooked confounding factor in microbiome studies and emphasize the utility of combining EHR with microbiome data to assess the impact of past medication use.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0107625"},"PeriodicalIF":4.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113570","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":"Metabolic capabilities of key rumen microbiota drive methane emissions in cattle.","authors":"Wanxin Lai, Antton Alberdi, Andy Leu, Arturo V P de Leon, Carl M Kobel, Velma T E Aho, Rainer Roehe, Phil B Pope, Torgeir R Hvidsten","doi":"10.1128/msystems.00601-25","DOIUrl":"https://doi.org/10.1128/msystems.00601-25","url":null,"abstract":"<p><p>The rumen microbiome plays a critical role in determining feed conversion and methane emissions in cattle, with significant implications for both agricultural productivity and environmental sustainability. In this study, we applied a hierarchical joint species distribution model to predict directional associations between biotic factors and abundances of microbial populations determined via metagenome-assembled genomes (MAGs). Our analysis revealed distinct microbial differences, including 191 MAGs significantly more abundant in animals with a higher methane yield (above 24 g/kg dry matter intake [DMI]; high-emission cattle), and 220 MAGs more abundant in low-emission cattle. Interestingly, the microbiome community of the low-methane-emission rumen exhibited higher metabolic capacity but with lower functional redundancy compared to that of high-methane-emission cattle. Our findings also suggest that microbiomes associated with low methane yields are prevalent in specific functionalities such as active fiber hydrolysis and succinate production, which may enhance their contributions to feed conversion in the host animal. This study provides an alternate genome-centric means to investigate the microbial ecology of the rumen and identify microbial and metabolic intervention targets that aim to reduce greenhouse gas emissions in livestock production systems.</p><p><strong>Importance: </strong>Ruminant livestock are major contributors to global methane emissions, largely through microbial fermentation in the rumen. Understanding how microbial communities vary between high- and low-methane-emitting animals is critical for identifying mitigation strategies. This study leverages a genome-centric approach to link microbial metabolic traits to methane output in cattle. By reconstructing and functionally characterizing hundreds of microbial genomes, we observe that a low-methane-emission rumen harbors well-balanced, \"streamlined\" microbial communities characterized by high metabolic capacity and minimal metabolic overlap across populations (low functional redundancy). Our results demonstrate the utility of genome-level functional profiling in uncovering microbial community traits tied to climate-relevant phenotypes.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0060125"},"PeriodicalIF":4.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113825","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":"Polysaccharide-degrading archaea dominate acidic hot springs: genomic and cultivation insights into a novel <i>Thermoproteota</i> lineage.","authors":"Maria I Prokofeva, Alina I Karaseva, Adolf S Tulenkov, Alexandra A Klyukina, Natalia E Suzina, Nicole J Bale, Anchelique Mets, Christa Schleper, Alexander G Elcheninov, Tatiana V Kochetkova","doi":"10.1128/msystems.00710-25","DOIUrl":"https://doi.org/10.1128/msystems.00710-25","url":null,"abstract":"<p><p>The expansion of sequencing technologies and bioinformatics has greatly advanced our understanding of microbial \"dark matter,\" yet the isolation of pure cultures, especially among Archaea, remains rare and challenging. Cultivation is still essential for the reliable characterization of microbial metabolism, which cannot be fully replaced by metagenomics and other omics-based approaches. Here, we report the first cultivated representatives of a deep-branching archaeal lineage previously known as <i>Candidatus</i> Marsarchaeota. Our phylogenomic analyses place these isolates within the phylum <i>Thermoproteota</i> as a novel order, <i>Tardisphaerales</i>. Members of <i>Tardisphaerales</i> dominate the prokaryotic communities in acidic hot springs below 70°C, comprising up to 40% of the total microbial population, underscoring their ecological significance. Functional genomics and culture experiments reveal a thermoacidophilic, anaerobic lifestyle, with energy metabolism based on carbohydrate fermentation, particularly of polysaccharides. This metabolic capability is supported by numerous glycosidase-encoding genes and by unprecedented metabolic versatility among thermoacidophiles. The isolates possess complete glycolysis, Entner-Doudoroff, and pentose-phosphate pathways, allowing them to utilize different sugars. Specialization in polysaccharide hydrolysis presumably provides an adaptive advantage for these slow-growing archaea, as most other heterotrophic thermoacidophiles prefer peptides or simple sugars. Furthermore, robust defense mechanisms against reactive oxygen species and persistence in acidic conditions enable <i>Tardisphaerales</i> to outcompete other heterotrophs and maintain dominance in these extreme habitats. The discovery and cultivation of this new order expand prokaryotic taxonomy and reveal the key players in carbon cycling in acidic geothermal ecosystems.IMPORTANCEMost of the dominant prokaryotes in natural environments remain uncultivated, and their metabolic potential and ecological role can be inferred solely from metagenomics. However, cultivation is essential for comprehensive functional characterization and identification of novel traits. Here, we describe the first cultivated representatives of the new archaeal order <i>Tardisphaerales</i> within the novel class <i>Tardisphaeria</i> (phylum <i>Thermoproteota</i>), a lineage abundant in acidic hot springs. Through the whole-genome reconstruction and microbiological experiments in pure cultures, we demonstrate that these archaea are metabolically distinct from the known thermoacidophiles, making them the key degraders of the complex organic matter in hot, acidic environments. Their genomes encode a diverse set of glycosidases that allow efficient polysaccharide breakdown at high temperatures and low pH, a trait with promising biotechnological applications.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0071025"},"PeriodicalIF":4.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113776","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":"Tracking putative <i>Microcystis</i> viruses and virus-host associations across distinct phases of a <i>Microcystis</i>-dominated bloom.","authors":"A J Wing, Bridget Hegarty, G Eric Bastien, Vincent J Denef, Jacob Evans, Gregory J Dick, Melissa B Duhaime","doi":"10.1128/msystems.00575-25","DOIUrl":"https://doi.org/10.1128/msystems.00575-25","url":null,"abstract":"<p><p>Viruses significantly impact microbial community composition and function. Yet their role in the fate of freshwater cyanobacterial harmful algal blooms (cHABs), an increasing threat to freshwater systems, remains poorly understood. Here, we address this with a metagenomic analysis of viruses of bloom-forming <i>Microcystis aeruginosa</i> through a seasonal cHAB in the western basin of Lake Erie. We identified globally distributed <i>Microcystis</i> viruses in Lake Erie based on sequence homology to well-studied isolates. A machine-learning model was then used to predict associations between uncharacterized viral populations and the <i>Microcystis</i> and non-<i>Microcystis</i> hosts of the cHAB. Size fractionation of water samples allowed us to identify significant fraction-specific trends in <i>Microcystis</i> viral diversity that corresponded with <i>Microcystis</i> genetic diversity. Viral diversity was highest in the non-colony-associated fraction and lowest in the colony-associated fraction, suggesting that colony formation may lead to bottlenecks in viral diversity in cHABs. Significant turnover of predicted <i>Microcystis</i> virus populations was observed through time, but not between stations miles apart. The virus-host networks revealed extensive interconnectivity and the potential for virus-mediated cross-species genetic exchange. The networks predicted that Lake Erie <i>Microcystis</i> viruses infect hosts spanning phyla, in agreement with lab studies in other systems but challenging previous notions of \"narrow\" host-virus associations in this genus. Abundant <i>Microcystis</i> virus genes revealed a potential role in key metabolic pathways and host adaptation. These findings advance our understanding of <i>Microcystis</i> viruses and their potential influence on host metabolism, species interactions, and coevolution in <i>Microcystis</i>-dominated cHABs.IMPORTANCEUnderstanding associations between viruses, their hosts, and environmental factors is key for identifying the mechanisms behind the rise and fall of cyanobacterial harmful algal blooms. This study explores the diversity and host ranges of viruses predicted to infect <i>Microcystis</i>, reporting how these properties vary over time, across sample stations in western Lake Erie, and among different filter size fractions. We found that <i>Microcystis</i> virus diversity is highest in non-colony-associated fractions and the lowest in colony-associated fractions, suggesting a link between <i>Microcystis</i> colony formation and reduced viral diversity. We identify abundant genes belonging to predicted <i>Microcystis</i> viruses and their potential roles in key metabolic pathways and adaptation to environmental changes. These findings enhance our understanding of the interplay among viruses, <i>Microcystis</i>, and co-occurring bacteria in cHABs, offering insights into the mechanisms driving bloom dynamics, species interactions, and coevolutionary processes.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0057525"},"PeriodicalIF":4.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113659","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":"Viral infection to the raphidophycean alga <i>Heterosigma akashiwo</i> affects both intracellular organic matter composition and dynamics of a coastal prokaryotic community.","authors":"Hiroaki Takebe, Haruna Hiromoto, Tetsuhiro Watanabe, Keigo Yamamoto, Keizo Nagasaki, Ryoma Kamikawa, Takashi Yoshida","doi":"10.1128/msystems.00816-25","DOIUrl":"https://doi.org/10.1128/msystems.00816-25","url":null,"abstract":"<p><p>Marine microalgae play a crucial role in the marine ecosystem by supplying dissolved organic matter to heterotrophic prokaryotes, which mediate the microbial loop. Microalgae are often infected by viruses, and in infected cells (virocells), the viruses modulate and often change the host metabolism for propagation and endo-metabolites. However, the impact of algal virocells on prokaryotic communities is not fully understood. In this study, we investigated whether lysates from virocells of <i>Heterosigma akashiwo,</i> a globally prevalent bloom-forming raphidophycean alga, cause shifts in prokaryotic community structure, and which metabolic compounds in the viral lysate might affect the surrounding prokaryotic populations. Using microcosm experiments, we cultured prokaryotic communities with a viral dissolved fraction (VDF) of <i>H. akashiwo</i>. Results revealed that certain prokaryotic populations assigned as <i>Vibrio</i> spp. pathogenic to fish and crustaceans grew specifically in response to the VDF. These <i>Vibrio</i> species possessed a gene module for branched-chain amino acids transporters, which were revealed to be enriched in VDF by gas chromatography-mass spectrometry analysis. Altogether, our findings suggest that viral infection-induced changes in biochemical properties of <i>H. akashiwo</i> cells can promote the growth of taxonomically and metabolically different prokaryotic populations, potentially impacting higher trophic-level consumers in marine ecosystems.IMPORTANCEThe primary production by marine microalgae and the consumption of the produced organic matter by prokaryotes significantly contribute to biogeochemical cycling. Microalgae are often infected by viruses, and in infected cells (virocells), the viruses modulate host metabolism for propagation and endo-metabolites. However, the impact of microalgal virocells on prokaryotic communities is not fully understood. This study investigates effects of lysates from virocells of <i>Heterosigma akashiwo</i>, a globally distributed harmful bloom-forming raphidophycean alga, on the prokaryotic community. Our data suggest that changes in biochemical properties in <i>H. akashiwo</i> virocells promoted the growth of specific bacterial populations that appeared to have metabolic capacity to utilize certain organic compounds enriched in the lysate. Additionally, as those populations included fish-pathogenic bacteria, we propose that viral infection to <i>H. akashiwo</i> can indirectly affect higher trophic-level consumers in marine ecosystems.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0081625"},"PeriodicalIF":4.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113692","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":"Ongoing evolution of PE/PPE genes in <i>Mycobacterium tuberculosis</i> associated with drug resistance and host immune response.","authors":"Mingyu Gan, Dan Wang, Suqing Li, Qinglan Wang, Qingyun Liu","doi":"10.1128/msystems.00898-25","DOIUrl":"https://doi.org/10.1128/msystems.00898-25","url":null,"abstract":"<p><p>The Proline-Glutamate/Proline-Proline-Glutamate (PE/PPE) gene family comprises approximately 10% of the <i>Mycobacterium tuberculosis</i> (Mtb) genome and is characterized by GC-rich, highly repetitive sequences. As a result, these genes are usually excluded from short-read-based whole-genome sequencing analyses, leaving their sequence diversity and evolutionary dynamics poorly characterized. Recently, a genome masking approach demonstrated that roughly 54% of PE/PPE sequences are recoverable from short-read data, providing an opportunity to examine the evolution of this gene family at a population level. Here, we analyzed 51,229 Mtb genomes to characterize sequence diversity and selection pressures across the PE/PPE gene family. Overall, we observed that PE/PPE genes are under relaxed purifying selection compared to other gene categories, as evidenced by higher ratios of nonsynonymous to synonymous polymorphisms (<i>pNpS</i>) and greater mutation burdens. We identified 12 PE/PPE genes with signatures of positive selection and 7 with selective pressure associated with antibiotic resistance. Among these genes, <i>PPE51</i> exhibited selection favoring loss-of-function mutations, which occurred only in Mtb strains that were already multidrug-resistant (MDR). This pattern suggests either compensatory evolution or adaptation related to resistance against second-line or newly introduced drugs. Additionally, we identified T-cell epitopes in six PE/PPE genes that were subject to diversifying selection, suggesting immune-driven adaptation. Collectively, this work provides a baseline characterization of genetic diversity in PE/PPE genes and highlights specific genes that may be involved in adaptation to host immunity and antibiotic pressure and represent candidates for further investigation.IMPORTANCETuberculosis remains a significant global health challenge, partly due to <i>Mycobacterium tuberculosis</i> (Mtb)'s remarkable evolutionary adaptation to antibiotics and human immune responses. Around 10% of its genome comprises PE/PPE genes, whose functions and evolutionary dynamics are poorly understood due to their repetitive sequences and high GC content. In this study, we analyzed 51,229 global Mtb genomes using an advanced genome-masking method, revealing numerous PE/PPE genes under positive selection, potentially facilitating antibiotic resistance and immune evasion. Notably, <i>PPE51</i> often loses its function in strains resistant to multiple antibiotics, suggesting a role in bacterial survival during drug treatment. Additionally, we identified mutation-prone regions within six PE/PPE genes, highlighting potential targets for future vaccine development. Collectively, our findings underscore the crucial role of PE/PPE genes in Mtb evolution and drug resistance, providing valuable insights to inform novel therapeutic and vaccine strategies.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0089825"},"PeriodicalIF":4.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113771","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":"Global phylogeography and genomic characterization of <i>bla</i>_NDM-1-positive clinical <i>Proteus mirabilis</i> isolates from China.","authors":"Jingyi Guo, Haotian Xu, Chengjin Wu, Hongyan Yu, Lexuan Yang, Yan Qi, Xiuyun Zuo, Hongyin Yang, Linyue Zhang, Yunsong Yu, Xi Li","doi":"10.1128/msystems.00758-25","DOIUrl":"https://doi.org/10.1128/msystems.00758-25","url":null,"abstract":"<p><p>Carbapenem-resistant <i>Proteus mirabilis</i> (CRPM), largely driven by dissemination of <i>bla</i>_NDM-1, poses a growing global threat, yet its phylogeographic and genetic patterns remain understudied. We analyzed 16 <i>bla</i>_NDM-1-harboring CRPM clinical isolates from a tertiary hospital in China (2017-2024) using antimicrobial susceptibility testing, conjugation assays, whole-genome sequencing, and growth experiments. We found that <i>bla</i>_NDM-1 dissemination occurred primarily via plasmids and Salmonella Genomic Island 1 (SGI1), including a novel SGI1-PM16 variant. Early transmission events were associated with Tn<i>125</i>-derived elements (ΔTn<i>125</i>), while IS<i>CR1</i> appeared to mediate rolling-circle transposition and likely facilitated local amplification of resistance cassettes. Additionally, we performed a global genomic epidemiological study of 420 <i>bla</i>_NDM-positive CRPM genomes curated from NCBI (accessed 21 April 2025). ST135 emerged as the predominant clone among CRPM in China. Phylogeographic analysis of <i>P. mirabilis</i> worldwide clarified the geographic prevalence of NDM variants. In the United States, <i>bla</i>_NDM-7 predominates, whereas <i>bla</i>_NDM-1 is most frequent in China. In summary, this study provides crucial insights into the resistance mechanisms and transmission dynamics of CRPM, as well as underscores the need to enhance genomic surveillance and optimize infection control strategies to mitigate the spread of <i>bla</i>_NDM-1-harboring CRPMs.</p><p><strong>Importance: </strong>To date, the phylogeographic distribution of <i>bla</i>_NDM-carrying CRPMs has not been determined. Our study identified ST135 as the predominant <i>bla</i>_NDM-producing clone, with a distinct global distribution pattern of NDM variants. Furthermore, we elucidated critical <i>bla</i>_NDM-1 transmission mechanisms, revealing both plasmid- and SGI1-mediated dissemination and IS<i>CR1</i>-driven gene amplification, while also characterizing a novel SGI1-PM16 variant. These findings provide significant new insights into the molecular mechanisms underlying acquired antimicrobial resistance.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0075825"},"PeriodicalIF":4.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113738","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 systems-level insight into PHB-driven metabolic adaptation orchestrated by the PHB-binding transcriptional regulator AniA (PhaR).","authors":"Antonio Lagares, Elizaveta Krol, Tina Jühling, Timo Glatter, Anke Becker","doi":"10.1128/msystems.00760-25","DOIUrl":"https://doi.org/10.1128/msystems.00760-25","url":null,"abstract":"<p><p>Poly(3-hydroxybutyrate) (PHB) is a carbon and energy storage polymer, whose accumulation under nutrient imbalances with excess carbon is common in bacteria. PhaR is a conserved transcriptional regulator that associates with PHB granules in several species. Although its role in modulating PHB storage and metabolism has been extensively studied across the bacterial phylogeny, a systems-level view of PhaR's dual function as a metabolic sensor and regulator is lacking. Here, we integrated co-expression network analysis with proteome profiling across multiple mutant backgrounds (lack of PhaR [AniA] and/or PHB synthesis) in the free-living state of the PHB-accumulating α-proteobacterial root nodule symbiont <i>Sinorhizobium meliloti</i>. This analysis was enriched by identifying direct regulatory targets of PhaR through a regulon-centric computational multistep search for DNA-binding site motifs combined with PhaR-DNA-binding and promoter-reporter assays. We confirmed that the model of accumulated PHB sequestering PhaR, and thereby relieving phasin and PHB depolymerase gene repression to control cellular PHB levels, also applies to <i>S. meliloti</i> and showed that PhaR-mediated regulation also occurs in the symbiotic state. Our integrated analyses of the impact of PHB-mediated PhaR titration on cellular functions revealed exopolysaccharide production as well as central carbon metabolism (<i>pdh</i> and <i>bkd</i>), gluconeogenesis (<i>ppdK</i> and <i>pyc),</i> entry into the TCA cycle (<i>gltA</i>)<i>,</i> and the initial steps of the Entner-Doudoroff (ED) pathway (<i>zwf, pgl,</i> and <i>edd</i>) as major regulatory targets, along with target genes of yet unknown function. Our findings highlight a pivotal role for PhaR in orchestrating carbon metabolism.IMPORTANCEPoly(3-hydroxybutyrate) (PHB) is a carbon and energy storage polymer typically associated with bacterial survival under nutrient-limited conditions. Its accumulation reflects the cellular metabolic balance, and the transcriptional regulator PhaR has been shown to bind PHB and control the expression of genes involved in its metabolism. At the same time, PhaR has been implicated in broader regulatory roles affecting global gene expression, although the connection between this function and its ability to sense PHB has remained unresolved. In this study, we used the model legume symbiont <i>Sinorhizobium meliloti</i> to bridge this gap. We demonstrated that PhaR modulates global gene expression in response to the metabolic state signaled by PHB accumulation. Our findings highlight PHB not only as a storage compound, but also as a key integrator of metabolic status that links nutrient availability to coordinated transcriptional responses.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0076025"},"PeriodicalIF":4.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113807","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":"The infection cycle of the haloarchaeal virus HFTV1 is tightly regulated and strongly inhibits motility of its host.","authors":"Sabine Schwarzer, Leonard E Bäcker, Jeroen G Nijland, Ismail Hayani Aji, Anne de Jong, Cristina Moraru, Claudia Steglich, Tessa E F Quax","doi":"10.1128/msystems.00704-25","DOIUrl":"10.1128/msystems.00704-25","url":null,"abstract":"<p><p>Although viruses have been shown to infect all domains of life, our understanding of the genetic program behind the exploitation of host resources to produce progeny virions is thus far limited to several bacterial viruses. Therefore, to elucidate the transcriptome of euryarchaeal viruses and their hosts, we employed RNAseq analysis of samples taken at different time points from <i>Haloferax gibbonsii</i> LR2-5 cultures infected with the lytic model virus Haloferax tailed virus 1 (HFTV1). While following the transcription of viral genes throughout the infective life cycle, we observed a tight temporal regulation of viral transcripts and differential expression from within viral gene clusters. Furthermore, antisense RNAs (asRNAs) appear to play an important role in support of the timing of late-expressed viral genes. Therefore, with many differentially expressed transcripts, including intragenic transcripts and asRNAs, the regulatory machinery employed by HFTV1 contrasts with that of viral model systems (based on phages), in which antitermination and/or alternative polymerases (seemingly lacking in HFTV1) are more widespread. When examining differentially expressed host genes, we observed a strong downregulation of genes involved in motility, such as those encoding the archaellum and chemotaxis machinery, which was confirmed by swimming assays of HFTV1 infected cells. This might be a strategy of the virus to redirect energy flowing into movement toward the production of virions. In conclusion, this work provides a stepping stone for further exploration of the intriguing strategies of viral transcriptional regulation throughout their infection cycle across the domains of life.IMPORTANCEViruses infect members of all three domains of life, including <i>Archaea. Euryarchaea</i> are widespread microorganisms found in various environments, such as the human gut and solar salterns. Due to the exceptional availability of cell biology and genetic tools for some salt-loving archaea, they serve as a model system from which insights can be extrapolated. Insights into the regulation of viral infections are of particular importance, especially since HFTV1 has been adopted as a model virus by the archaeal viral community. We found that, while harboring parallels with bacterial viruses, such as tight temporal regulation, HFTV1 harbors an impressive number of differentially expressed transcriptional units. Furthermore, antisense RNAs and intragenic regulatory elements seem to play a much more prominent role in HFTV1 gene expression. Thus, this work challenges current models and provides valuable new insights into the gene regulation of viral infection of archaea, which mark similarities and differences with viruses from other domains of life.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0070425"},"PeriodicalIF":4.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113681","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":"Region-specific genomic variation and functional divergence of <i>Helicobacter pylori</i> clinical isolates from the gastric antrum and corpus.","authors":"Chih-Ho Lai, Shih-Yu Wu, Shiao-Wen Li, Quan N U Ho, Ruei-Lin Chiang, Ngoc-Niem Bui, Hui-Yu Wu, Yu-Tsen Huang, Cheng-Hsun Chiu, Wen-Ching Wang","doi":"10.1128/msystems.01029-25","DOIUrl":"https://doi.org/10.1128/msystems.01029-25","url":null,"abstract":"<p><p>The genetic variability of <i>Helicobacter pylori</i> contributes to differences in the severity of gastrointestinal diseases. Within the stomach, <i>H. pylori</i> exhibits diverse strain patterns and genetic variations that enable the evolution of new virulence factors, development of antibiotic resistance, and evasion of the host immune system. However, the comprehensive analysis of whole-genome sequences and their functional impact on gastric epithelial cells remains limited. In this study, we performed whole-genome sequencing, <i>de novo</i> assembly, and comparative genomic analysis on two pairs of <i>H. pylori</i> strains (v225/v226 and v290/v291) isolated from the antrum and corpus of two peptic ulcer patients. Bioinformatic tools were used to annotate and compare genes related to adhesion and virulence. Functional assays were conducted to assess strain-specific pathogenic effects on gastric epithelial cells. The analyses revealed substantial genetic heterogeneity between antral and corpus isolates, particularly in adhesion-related genes (<i>sabA</i>, <i>babA/B</i>), the cytotoxin-associated gene pathogenicity island (<i>cag</i>-PAI) cluster, and <i>vacA</i> sequences. Functional assays demonstrated region-specific differences, with corpus strains showing stronger adhesion and pro-inflammatory responses, whereas antral strains exhibited higher vacuolating activity. These findings demonstrate the ability of <i>H. pylori</i> to colonize specific stomach regions, undergo genetic diversification, and evolve niche-specific adaptations and pathogenicity in different gastric environments.IMPORTANCE<i>Helicobacter pylori</i> is a major cause of severe gastrointestinal diseases. It can establish persistent colonization in different regions of the stomach, where distinct environmental conditions drive niche-specific adaptation. Here, we found that <i>H. pylori</i> evolves genetic diversity in various factors, including virulence factors, adhesion molecules, and outer membrane proteins, to facilitate persistent colonization. Understanding how <i>H. pylori</i> generates genetic diversity to support colonization is crucial for developing more effective infection management strategies, improving molecular detection, and refining personalized treatment approaches.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0102925"},"PeriodicalIF":4.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113481","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}