Microbial Cell最新文献

{"title":"Scp160 deletion suppresses TDP-43 aggregation and toxicity in <i>Saccharomyces cerevisiae</i>.","authors":"Joan Castells-Ballester, Natalia Shcherbik","doi":"10.15698/mic2026.10.888","DOIUrl":"https://doi.org/10.15698/mic2026.10.888","url":null,"abstract":"<p><p>Protein misfolding and aberrant protein aggregation are central features of neurodegenerative disorders, including amyotrophic lateral sclerosis, where the RNA-binding protein TDP-43 accumulates in abnormal intracellular assemblies. Although yeast models have identified multiple modifiers of TDP-43 toxicity, the cellular factors that determine how aggregation-prone proteins are organized remain incompletely understood. Here, we investigated whether the ribosome- and mRNP-associated proteins Scp160 and Bfr1 influence TDP-43 proteotoxicity and aggregate formation. We report that deletion of <i>SCP160</i> or <i>BFR1</i> improves growth during TDP43-GFP induction without reducing steady-state reporter abundance and decreases formation of prominent TDP43-GFP foci. Deletion of <i>BFR1</i> produced an intermediate TDP-43 phenotype, with a weaker effect than <i>SCP160</i> deletion on severe foci formation and toxicity. Importantly, the effect of <i>SCP160</i> or <i>BFR1</i> deletion on visible protein aggregation was not specific to TDP-43: severe Htt103Q-GFP aggregation was strongly reduced, and formation of VHL-GFP foci was suppressed, including under conditions of proteasome inhibition. Despite these shared effects, the two mutants were not phenotypically identical. Deletion of <i>SCP160</i> produced a distinct spatial phenotype in which residual TDP43-GFP foci showed markedly increased association with Sec63-positive ER structures and reduced distance to these regions, whereas <i>bfr1</i> <math><mi>Δ</mi></math> cells did not show the same Sec63-associated shift. Together, these findings uncouple TDP43-GFP abundance from toxicity and prominent foci formation and identify Scp160 and Bfr1 as factors that influence the intracellular partitioning of aggregation-prone and misfolded proteins, with an additional role for Scp160 in the spatial organization of TDP43 relative to the ER.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"13 ","pages":"358-377"},"PeriodicalIF":4.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The p53 DNA-Binding (Core) Domain can form a prion that seeds prion formation in full-length p53.","authors":"Mathilde Kadouch, Christelle Marchal, Sei-Kyoung Park, Sangeun Park, Sabine Castano, Susan W Liebman, Christophe Cullin","doi":"10.15698/mic2026.10.887","DOIUrl":"10.15698/mic2026.10.887","url":null,"abstract":"<p><p>The p53 tumor suppressor is frequently inactivated in human cancers, often through mutations in its core-domain. Here, we developed a yeast reporter system in <i>S. cerevisiae</i> to investigate whether the p53 core-domain can function as a prion-forming domain. By using a chimeric protein (CD-FDp) combining the p53 <b>C</b>ore <b>D</b>omain and the <b>F</b>unctional <b>D</b>omain of the yeast prion protein Ure2p, we demonstrate that inactive CD-FDp forms heritable, self-propagating aggregates. These aggregates exhibit canonical prion properties, including dominance, non-Mendelian segregation, and cytoduction-mediated transmission. CD-FDp prionization is independent of canonical chaperones (Hsp104, Hsp70, Hsp90), distinguishing it from classical yeast prions. Prionized CD-FDp enhances the formation of amyloid-like foci in full-length p53-EYFP, as evidenced by Thioflavin T staining, and can transmit its prion state to full-length p53 via cytoplasmic transfer. This indicates that CD-FDp propagons can induce structural conversion of p53, supporting an autocatalytic aggregation model. Using a Luria-Delbrück fluctuation assay, we quantified the prionization propensity of wild-type and cancer-associated p53 core-domain mutants. While most mutants (e.g., R273H, R282W) showed inactivation frequencies similar to wild-type, the R175H mutant exhibited an <math><mo>∼</mo></math> 18-fold increase in prionization frequency, which correlates with its known aggregation propensity in human cancers. This yeast system thus provides a quantitative platform to assess the prion-like behavior of p53 mutants and screen for inhibitors of p53 inactivation. Our findings establish p53 core-domain as a novel, structurally distinct prion-forming domain and offer a powerful experimental framework for studying p53 inactivation mechanisms, with potential implications for cancer therapeutics.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"13 ","pages":"340-357"},"PeriodicalIF":4.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sorbic acid triggers rapid formation of proteasome storage granules in <i>Saccharomyces cerevisiae</i>.","authors":"Shoei Tanaka, Mitsuki Imajo, Mieko Hayashi, Akira Matsuura, Shingo Izawa","doi":"10.15698/mic2026.08.886","DOIUrl":"10.15698/mic2026.08.886","url":null,"abstract":"<p><p>Proteasomes are primarily located within the nuclei of proliferating cells; however, their localization changes dynamically in response to environmental conditions. <i>Saccharomyces cerevisiae</i> forms proteasome storage granules (PSGs) in the cytoplasm upon glucose depletion, mitochondrial stress, transition to quiescence, or acetic acid stress, with intracellular acidification acting as a key trigger. Despite possessing similar dissociation constants, sorbic acid and acetic acid are noted to exert different physiological effects on yeast cells. In this study, we demonstrate that sorbic acid induces the fastest PSG formation ever reported (within 30 min) at lower concentrations than acetic acid, accompanied by the inhibition of proteasomal proteolysis. Conversely, our analysis of the required factors revealed that, similar to acetic acid, the proteasome subunits Sem1 and Rpn13 are essential for sorbic acid-induced PSG formation. In contrast, the shuttle factors Dsk2 and Rad23, along with the E3 ubiquitin ligase Hul5-which are required for PSG formation under mitochondrial stress or quiescence-are dispensable for sorbic acid-induced PSG formation. These findings not only identify a novel condition for rapid PSG formation but also provide new insights into the physiological effects of sorbic acid on the proteasome, highlighting both its similarities to and differences from acetic acid.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"13 ","pages":"329-339"},"PeriodicalIF":4.1,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Saccharomyces cerevisiae</i> in cancer research: modeling tumor biology and enabling drug discovery.","authors":"Graziana Assalve, Paola Lunetti, Annalisa Fai, Luca Frattaruolo, Anna Rita Cappello, Alessandra Ferramosca, Vincenzo Zara","doi":"10.15698/mic2026.08.885","DOIUrl":"10.15698/mic2026.08.885","url":null,"abstract":"<p><p>Cancer is a complex disease driven by genetic, metabolic, and environmental alterations, whose investigation is often constrained by the limited tractability of mammalian systems. The budding yeast <i>Saccharomyces cerevisiae</i> has emerged as a powerful eukaryotic model to study conserved cellular processes relevant to tumor biology in a simplified and scalable context and as a versatile platform for translational and biotechnological applications. Through genetic manipulation and heterologous expression, yeast allows systematic analysis of human cancer genes and variants, providing quantitative insights into their functional impact. In parallel, yeast reproduces fundamental features of cancer cell metabolism and stress adaptation, offering a controlled system to investigate cellular responses to environmental constraints. The conservation of major DNA repair and autophagy pathways further supports the use of yeast to study genome stability and survival mechanisms in cancer. Beyond its role in basic research, <i>S. cerevisiae</i> represents a scalable platform for anticancer drug discovery, enabling systematic identification of drug targets, resistance mechanisms, and genotype-specific vulnerabilities through high-throughput and engineered strain-based approaches. Continued development of yeast platforms, together with synthetic biology, functional genomics, and advanced genomic technologies, is expected to accelerate therapeutic innovation and improve our understanding of cancer biology. This review discusses recent advances in yeast-based cancer research, highlighting the contribution of engineered yeast platforms to the investigation of oncogenic signaling, metabolic rewiring, stress adaptation, DNA repair, and autophagy, reinforcing the role of yeast at the interface between cancer research and biotechnology.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"13 ","pages":"314-328"},"PeriodicalIF":4.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13443094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A time-resolved high-throughput screening of fission yeast deletion mutants for oxidative stress resistance.","authors":"Mohammadtaha Pirsalehi, Rowshan Ara Islam, Kristal Ng, Olga Xintarakou, Peter Harold Thorpe, Charalampos Rallis","doi":"10.15698/mic2026.07.884","DOIUrl":"10.15698/mic2026.07.884","url":null,"abstract":"<p><p>Cells typically balance growth with stress responses - growing rapidly in low stress conditions and halting growth to defend against stress or to repair stress-induced damage. While numerous genome-wide screens have identified mutants resistant to oxidative stress, these have largely relied on static, end-point measurements. Here, we take a dynamic, time-resolved approach to uncover how fission yeast, <i>Schizosaccharomyces pombe,</i> adapts to oxidative stress over time. We have tracked the growth of 3,420 deletion mutants across nine time points spanning four days on both nutrient-rich solid media and media containing oxidative stress induced by hydrogen peroxide. This kinetic strategy revealed not just resistant or sensitive mutants. It allowed clustering of growth patterns across time and uncovered mutants that are capable of transiently uncoupling growth from stress response. Hydrogen peroxide induced a dose-dependent delay in colony expansion in most deletion strains, yet 15 mutants consistently maintained robust growth. These belong to different functional categories, highlighting diverse potential mechanisms ranging from altered DNA damage checkpoints to metabolic rewiring and growth regulation. By capturing dynamic trajectories rather than static outcomes, this study exposes hidden layers of growth under oxidative stress and identifies new genetic determinants of cellular resilience in fission yeast.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"13 ","pages":"304-313"},"PeriodicalIF":4.1,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal spread and environmental persistence of carbapenem-resistant high-risk <i>Pseudomonas aeruginosa</i> in critical-care units of a Chilean national referral center for burn and trauma patients (2022).","authors":"Camila Ibarra, Gustavo Araya, Alhejandra Alvarez, Leonardo Enríquez, Carolina Arellano, Fabricio Alarcón, Constanza Fernández, Claudio Vargas, Rodrigo Vera, Roberto M Vidal","doi":"10.15698/mic2026.07.883","DOIUrl":"10.15698/mic2026.07.883","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> is an opportunistic nosocomial pathogen ranked by the World Health Organization (WHO) as a high priority for research and the development of new antimicrobial therapies. To characterize carbapenem-resistant <i>P. aeruginosa</i> (CRPA) isolated from patients at the Hospital de Urgencia Asistencia Pública (HUAP), Chile in 2022, and to evaluate clonal diversity, resistance mechanisms, virulence factors, and clinical associations. We analyzed 126 clinical CRPA isolates using PFGE, PCR screening of resistance and virulence genes, and whole-genome sequencing of 18 representative strains. Sequence types (STs), resistomes, and virulomes were identified, and their associations with severity, length of hospital stay, cost, and patient outcomes were evaluated. Seventy-four percent of isolates originated from critical care units, predominantly from respiratory and tissue samples. PFGE revealed 25 pulsotypes, with L and Y being the predominant types. Overall, 67% of isolates were XDR and 1% PDR. Carbapenemase genes were absent in 115 isolates, while <i>blaVIM</i> and <i>blaKPC</i> were detected in 8 and 3 isolates, respectively. The <i>exoS</i> ⁺/<i>exoU</i> ⁺ genotype was identified in 6 isolates; whole-genome sequencing revealed eight distinct STs, including previously described high-risk clones ST654, ST395, and ST274. A resistome analysis revealed diverse aminoglycoside and <math><mi>β</mi></math> -lactam resistance determinants, while a virulome analysis confirmed the presence of <i>exoS</i> ⁺/<i>exoU</i> ⁺ in two sequenced isolates. Carbapenem resistance was significantly associated with prolonged hospitalization (median 84 vs. 39 days), greater clinical severity, and substantially higher healthcare resource utilization, reflected by increased DRG (Diagnosis-Related Group) weights, compared with carbapenem-susceptible controls. Our findings highlight the circulation of high-risk <i>P. aeruginosa</i> clones in Chile and underscore the importance of molecular epidemiology in guiding infection control, optimizing antimicrobial therapy, and mitigating the clinical and economic burden of CRPA.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"13 ","pages":"293-303"},"PeriodicalIF":4.1,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The transcriptome of dendritic cells redraws the boundaries between pathogenicity and commensalism in yeast.","authors":"Lisa Rizzetto, Irene Stefanini, Stefano Nenciarini, Monica Di Paola, Samantha Riccadonna, Ivo G Gut, Marta Gut, Simon Heath, Duccio Cavalieri","doi":"10.15698/mic2026.07.882","DOIUrl":"10.15698/mic2026.07.882","url":null,"abstract":"<p><p>Our immune system is constantly exposed to fungi, but it mounts a consistent, disease-related, and species-specific inflammatory response only against a few fungal species. Most of the current understanding of fungus-host interactions is based on a limited number of strains, hence neglecting the fungal intra-specific genetic and phenotypic diversity. To expand our knowledge of the spectrum of immune responses to pathogenic and non-pathogenic fungi, we compared the cytokine and transcriptional profiles of human monocyte-derived dendritic cells exposed to <i>Aspergillus fumigatus</i>, <i>Candida albicans</i>, <i>Candida parapsilosis</i>, and <i>Saccharomyces cerevisiae</i> strains. The tested species triggered common and species-specific responses, mostly resulting from the different timing of signaling pathways. Faster phagolysosome acidification was observed for pathogenic species. These results highlight the urgency to redraw the boundaries between pathogenicity and commensalism in fungi, shining a spotlight on the timing of the response, rather than solely on the genes triggered by the stimuli.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"13 ","pages":"282-292"},"PeriodicalIF":4.1,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13365740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yippee-like protein Moh1 links gene expression to metabolism and selective stress resistance in <i>Saccharomyces cerevisiae</i>.","authors":"Çağla Ece Olgun, Gizem Turan Duman, Gizem Güpür, Hamit İzgi, Mariam Huda, Demet Çetin, Zekiye Suludere, Fatma Küçük Baloğlu, Ayşe Koca Çaydaşı, Mesut Muyan","doi":"10.15698/mic2026.06.881","DOIUrl":"10.15698/mic2026.06.881","url":null,"abstract":"<p><p>The Yippee-like (YPEL) proteins are a evolutionarily conserved eukaryotic family implicated in proliferation, senescence, and stress adaptation, yet their molecular functions remain poorly defined. Humans possess five paralogs (YPEL1-YPEL5), while the budding yeast <i>S. cerevisiae</i> contains a single ortholog, <i>MOH1</i>, previously linked to stress responses but with an unclear cellular role. Here, we investigated the function of <i>MOH1</i> in <i>S. cerevisiae</i>. <i>MOH1</i> deletion resulted in stress-specific phenotypes, including increased sensitivity to sodium azide and sulfuric acid, but enhanced resistance to hydrogen peroxide and acetic acid. Moh1 protein levels were dynamically regulated, decreasing upon hydrogen peroxide treatment and increasing in response to sulfuric acid. Morphological analyses including SEM revealed that <i>moh1</i> <math><mi>Δ</mi></math> cells are rounder, form aggregates, and exhibit altered surface architecture independently of stress. RNA profiling and FTIR spectroscopy uncovered transcriptional reprogramming and metabolic remodeling, including alterations in lipid, protein, and cell wall polysaccharide levels and composition. Functional analyses showed that increased resistance to hydrogen peroxide is not due to altered mitochondrial ROS production but rather to reduced intracellular ROS accumulation. This effect is attributed to decreased cellular uptake resulting from altered permeability, supported by resistance to Congo red and sensitivity to SDS, consistent with cell envelope remodeling. Collectively, our findings identify Moh1 as a regulatory factor linking gene expression to metabolism and cellular architecture, thereby influencing cell envelope permeability and conferring selective stress resistance in <i>S. cerevisiae</i>.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"13 ","pages":"261-281"},"PeriodicalIF":4.1,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13329494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<ArticleTitle xmlns:ns0=\"http://www.w3.org/1998/Math/MathML\">Fungistatic effect of sorbic acid on yeast cells via translational repression involving eIF2 <ns0:math><ns0:mi>α</ns0:mi></ns0:math> phosphorylation and formation of Ded1- and eIF2B-granules.","authors":"Haruka Yoshiyama, Wataru Nomura, Shingo Izawa","doi":"10.15698/mic2026.06.880","DOIUrl":"10.15698/mic2026.06.880","url":null,"abstract":"<p><p>Sorbic acid is a lipophilic weak acid with fungistatic activity, and it has been widely used as a food preservative, along with its potassium and calcium salts. Although the fungistatic effect of sorbic acid is thought to be primarily due to acidification within fungal cells, the detailed fungistatic mechanism remains unclear. We investigated the effects of sorbic acid on yeast translation in <i>Saccharomyces cerevisiae</i>. At sublethal concentrations (2-4 mM), sorbic acid quickly repressed translation. Conversely, removal of sorbic acid restored translation activity, indicating that the sorbic acid-induced translational repression is reversible. Pronounced translational repression induced by various stress conditions or nutrient starvation is often accompanied by eIF2 <math><mi>α</mi></math> phosphorylation, eIF2B-body and stress granule (SG) formation, and the sequestration of Ded1 (which plays a role in translation initiation as a DEAD-box RNA helicase) into SGs. We found that sorbic acid stress also induces eIF2 <math><mi>α</mi></math> phosphorylation and the sequestration of Ded1 into SGs. In contrast, sorbic acid stress induced the formation of not eIF2B bodies but eIF2B granules, which colocalized with SGs. These results suggest that the functional arrest of translation-related factors, including eIF2 <math><mi>α</mi></math> , eIF2B, and Ded1, correlates strongly with the translational repression in the presence of sorbic acid. Notably, Gcn2 deficiency delayed translational repression and SG formation, and significantly suppressed eIF2B granule formation, suggesting the involvement of Gcn2 in these stress responses during sorbic acid stress. Our findings provide new insights into the physiological effects of sorbic acid on yeast cells, specifically regarding the regulation of translation-related factors.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"13 ","pages":"250-260"},"PeriodicalIF":4.1,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Occlusal types shape oral microbiome stomatotypes and metabolic landscapes: A multi-omics perspective on host-microbe interaction.","authors":"Yufeng Duan, Zheng Liu, Wenting Lu, Ning Zhao, Lingjun Yuan, Zhenxia Li, Ting Zhou, Shengzhao Xiao, Dian Jing, Xiaowen Zheng, Wentao Shi, Chao Liu, Haixia Lu, Qiang Feng, Bing Fang","doi":"10.15698/mic2026.06.879","DOIUrl":"10.15698/mic2026.06.879","url":null,"abstract":"<p><p>Clinical studies have uncovered associations between malocclusions and bacteria-related oral diseases. However, which malocclusion drives alternations in the oral microbiome remains unclear. Here, we identified occlusal type (OT, a major malocclusion classification parameter) as a key host structural regulator of the oral microbiome composition and metabolite profiles in adolescents. Regarding microbial composition: <i>Prevotella</i> and <i>Veillonella</i> species enriched in the OT-I group, whereas <i>Neisseria</i> and <i>Haemophilus</i> species predominated in the OT-II group. These differential distributions and unique microbial associations contributed to the formation of two distinct oral microbiome clusters (\"stomatotypes\"). In terms of gene functions, the OT-II group exhibited enrichment in \"Environmental information processing\" (EIP) pathways, \"Human Diseases\" (HD) pathways, and virulence-associated genes including relA and cpsB/cdsA. Significant differences in metabolite profiles were also observed between groups. Multi-omics analysis revealed positive intra-group associations and negative associations between-groups among representative oral microbes, functional pathways, and metabolites, with specific dipeptides identified as potential key microbe-modulated metabolites. Our results revealed the pivotal role of OT in shaping the variations of the oral microbiome and metabolite, offering novel insights into how host anatomical structure influences oral microecology.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"13 ","pages":"237-249"},"PeriodicalIF":4.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13320636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}