Pub Date : 2026-01-12DOI: 10.1038/s41564-025-02244-9
Pernille Neve Myers, Rasmus Kaae Dehli, Axel Mie, Janne Marie Moll, Henrik Munch Roager, Carsten Eriksen, Martin Frederik Laursen, Ellen Magdalena Staudinger, Ioanna Chatzigiannidou, Pi Lærke Johansen, Niels van Best, Martin O’Hely, Daniel Andersen, Nadja Lund Nørregaard, Mikael Pedersen, Eckard Hamelmann, Susanne Lau, Martin Iain Bahl, Maher Abou Hachem, Tine Rask Licht, Henrik Bjørn Nielsen, Anna Hammerich Thysen, Peter Vuillermin, John Penders, Karsten Kristiansen, Annika Scheynius, Johan Alm, Susanne Brix
Early-life microbial exposures shape immune development and allergy risk. Food allergen sensitization, reflected by the presence of food allergen-specific immunoglobulin E (IgE), is an early indication of impaired immune tolerance. Here we show that early-life transmission of aromatic lactate-producing bifidobacteria strains in 147 children followed from birth to 5 years of age, facilitated by vaginal delivery, exposure to older siblings and exclusive breastfeeding for the first 2 months, led to increased levels of aromatic lactates in the infant gut. This microbiota–metabolite signature was inversely associated with the development of food allergen-specific IgE until 5 years and atopic dermatitis at 2 years. The observed effect was mediated by 4-hydroxy-phenyllactate, which inhibited IgE, but not IgG, production in ex vivo human immune cell cultures. Together, these findings define an early-life microbiota–metabolite–immune axis linking microbial transmission and feeding practices with reduced allergic sensitization. Vaginal birth, exclusive breastfeeding and early contact with siblings promote colonization of the infant gut with bifidobacteria capable of producing aromatic lactates, a microbial and metabolite signal that is inversely related to the risk of allergen-specific sensitization and dermatitis later in life.
{"title":"Early-life colonization by aromatic-lactate-producing bifidobacteria lowers the risk of allergic sensitization","authors":"Pernille Neve Myers, Rasmus Kaae Dehli, Axel Mie, Janne Marie Moll, Henrik Munch Roager, Carsten Eriksen, Martin Frederik Laursen, Ellen Magdalena Staudinger, Ioanna Chatzigiannidou, Pi Lærke Johansen, Niels van Best, Martin O’Hely, Daniel Andersen, Nadja Lund Nørregaard, Mikael Pedersen, Eckard Hamelmann, Susanne Lau, Martin Iain Bahl, Maher Abou Hachem, Tine Rask Licht, Henrik Bjørn Nielsen, Anna Hammerich Thysen, Peter Vuillermin, John Penders, Karsten Kristiansen, Annika Scheynius, Johan Alm, Susanne Brix","doi":"10.1038/s41564-025-02244-9","DOIUrl":"10.1038/s41564-025-02244-9","url":null,"abstract":"Early-life microbial exposures shape immune development and allergy risk. Food allergen sensitization, reflected by the presence of food allergen-specific immunoglobulin E (IgE), is an early indication of impaired immune tolerance. Here we show that early-life transmission of aromatic lactate-producing bifidobacteria strains in 147 children followed from birth to 5 years of age, facilitated by vaginal delivery, exposure to older siblings and exclusive breastfeeding for the first 2 months, led to increased levels of aromatic lactates in the infant gut. This microbiota–metabolite signature was inversely associated with the development of food allergen-specific IgE until 5 years and atopic dermatitis at 2 years. The observed effect was mediated by 4-hydroxy-phenyllactate, which inhibited IgE, but not IgG, production in ex vivo human immune cell cultures. Together, these findings define an early-life microbiota–metabolite–immune axis linking microbial transmission and feeding practices with reduced allergic sensitization. Vaginal birth, exclusive breastfeeding and early contact with siblings promote colonization of the infant gut with bifidobacteria capable of producing aromatic lactates, a microbial and metabolite signal that is inversely related to the risk of allergen-specific sensitization and dermatitis later in life.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"429-441"},"PeriodicalIF":19.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1038/s41564-025-02251-w
Baptiste Pradel, Maximiliano G. Gutierrez
Single-cell profiling of antibiotic-driven bacterial cell death predicts in vivo treatment outcomes against mycobacteria and could improve treatment guidance.
抗生素驱动的细菌细胞死亡的单细胞分析可以预测体内治疗分枝杆菌的结果，并可以改善治疗指导。
{"title":"Measuring bacterial killing to predict antibiotic treatment outcomes","authors":"Baptiste Pradel, Maximiliano G. Gutierrez","doi":"10.1038/s41564-025-02251-w","DOIUrl":"10.1038/s41564-025-02251-w","url":null,"abstract":"Single-cell profiling of antibiotic-driven bacterial cell death predicts in vivo treatment outcomes against mycobacteria and could improve treatment guidance.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"341-342"},"PeriodicalIF":19.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1038/s41564-025-02248-5
Xueyin Feng,Shoichi Tachiyama,Jing He,Siqi Zhu,Hang Zhao,Jack M Botting,Yanran Liu,Yuanyuan Chen,Canfeng Hua,María Lara-Tejero,Matthew A B Baker,Xiang Gao,Jun Liu,Beile Gao
Knowledge of bacterial flagella has largely come from studies of the simpler motors of Escherichia coli and Salmonella enterica. However, many bacteria harbour more complex motors. The function, mechanisms and evolution associated with such auxiliary motor structures are unclear. Here we deploy structural, genetic, biochemical and functional approaches to characterize complex adaptations of the flagellar motor in Campylobacter jejuni. We observed an E ring formed by 17 FlgY homodimers around the MS ring, a cage-like structure made of FcpMNO and PflD, and PflA-PflB interactions in a spoke-rim formation between the E ring and cage. These scaffolds stabilized the 17 torque-generating stator complexes. Phylogenetic analyses suggest an ancient origin and widespread prevalence of the E ring and spokes across diverse flagellated bacteria, and co-option of type IV pilus components in the ancestral motor of phylum Campylobacterota. Collectively, these data provide insight into the assembly, function and evolution of complex flagellar motors.
{"title":"Structural insights into the assembly and evolution of a complex bacterial flagellar motor.","authors":"Xueyin Feng,Shoichi Tachiyama,Jing He,Siqi Zhu,Hang Zhao,Jack M Botting,Yanran Liu,Yuanyuan Chen,Canfeng Hua,María Lara-Tejero,Matthew A B Baker,Xiang Gao,Jun Liu,Beile Gao","doi":"10.1038/s41564-025-02248-5","DOIUrl":"https://doi.org/10.1038/s41564-025-02248-5","url":null,"abstract":"Knowledge of bacterial flagella has largely come from studies of the simpler motors of Escherichia coli and Salmonella enterica. However, many bacteria harbour more complex motors. The function, mechanisms and evolution associated with such auxiliary motor structures are unclear. Here we deploy structural, genetic, biochemical and functional approaches to characterize complex adaptations of the flagellar motor in Campylobacter jejuni. We observed an E ring formed by 17 FlgY homodimers around the MS ring, a cage-like structure made of FcpMNO and PflD, and PflA-PflB interactions in a spoke-rim formation between the E ring and cage. These scaffolds stabilized the 17 torque-generating stator complexes. Phylogenetic analyses suggest an ancient origin and widespread prevalence of the E ring and spokes across diverse flagellated bacteria, and co-option of type IV pilus components in the ancestral motor of phylum Campylobacterota. Collectively, these data provide insight into the assembly, function and evolution of complex flagellar motors.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"5 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Many eukaryotic viruses, including amoeba-infecting mimiviruses, have codon usage that deviates from their hosts. However, codon usage patterns that align with the cellular tRNA pool enable efficient translation. How these viruses cope with the mismatch between tRNA supply and demand is unclear. Here we show that Acanthamoeba polyphaga mimivirus (APMV) generates a subcellular area to translate viral mRNAs. tRNA sequencing showed that the tRNA pool was not substantially altered during the infection, even though the virus encodes tRNA genes. Using in situ labelling, we found that viral mRNAs and newly synthesized proteins were localized in the periphery of the viral factory, suggesting that APMV creates a discrete subcellular environment to facilitate translation. Frequently used codons in viral mRNAs had higher tRNA accessibility than the same type of codons in amoeba mRNAs. Our data show how local translation assists the virus in overcoming the mismatch between tRNA supply and demand. Acanthamoeba polyphaga mimivirus generates a subcellular area in host cells that overcomes the mismatch between host and viral tRNA supply and demand.
{"title":"A giant virus forms a specialized subcellular environment within its amoeba host for efficient translation","authors":"Ruixuan Zhang, Lotte Mayer, Hiroyuki Hikida, Yuichi Shichino, Mari Mito, Anouk Willemsen, Shintaro Iwasaki, Hiroyuki Ogata","doi":"10.1038/s41564-025-02234-x","DOIUrl":"10.1038/s41564-025-02234-x","url":null,"abstract":"Many eukaryotic viruses, including amoeba-infecting mimiviruses, have codon usage that deviates from their hosts. However, codon usage patterns that align with the cellular tRNA pool enable efficient translation. How these viruses cope with the mismatch between tRNA supply and demand is unclear. Here we show that Acanthamoeba polyphaga mimivirus (APMV) generates a subcellular area to translate viral mRNAs. tRNA sequencing showed that the tRNA pool was not substantially altered during the infection, even though the virus encodes tRNA genes. Using in situ labelling, we found that viral mRNAs and newly synthesized proteins were localized in the periphery of the viral factory, suggesting that APMV creates a discrete subcellular environment to facilitate translation. Frequently used codons in viral mRNAs had higher tRNA accessibility than the same type of codons in amoeba mRNAs. Our data show how local translation assists the virus in overcoming the mismatch between tRNA supply and demand. Acanthamoeba polyphaga mimivirus generates a subcellular area in host cells that overcomes the mismatch between host and viral tRNA supply and demand.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"584-596"},"PeriodicalIF":19.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02234-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The intestinal epithelium relies on continuous stem cell-driven renewal to maintain barrier function and recover from injury. While bacterial signals are known to influence intestinal stem cell behaviour, the regenerative capacity of the gut mycobiome has remained largely unexplored. Here we identify the commensal fungus Kazachstania pintolopesii (Kp) as a critical mediator of intestinal regeneration through its secreted protein Ygp1. We found that a 12-amino acid peptide fragment of Ygp1, CD12, was sufficient to promote intestinal organoid differentiation and accelerate intestinal healing in murine models of colitis and chemotherapy-induced injury. Transcriptomics, simulations and molecular interaction experiments revealed that CD12 binds mammalian α-enolase (ENO1), enhancing YAP1 (Yes-associated protein 1) protein levels and activating regenerative transcriptional programmes through the Hippo signalling pathway. Engineered probiotics expressing CD12 replicated its therapeutic benefits, offering a translatable delivery strategy. Our work expands the therapeutic potential of the mycobiome, positioning it as a source of biologics for inflammatory and iatrogenic gut disorders. A short peptide derived from a commensal-fungal-secreted protein promotes repair in models of colon epithelial damage when delivered directly or via probiotic microbes.
肠上皮依赖于干细胞驱动的持续更新来维持屏障功能并从损伤中恢复。虽然已知细菌信号会影响肠道干细胞的行为，但肠道菌群的再生能力在很大程度上仍未被探索。在这里，我们发现共生真菌Kazachstania pintolopesii （Kp）通过其分泌的蛋白Ygp1作为肠道再生的关键介质。我们发现，在小鼠结肠炎和化疗损伤模型中，Ygp1的一个12个氨基酸肽片段CD12足以促进肠道类器官分化并加速肠道愈合。转录组学、模拟和分子相互作用实验表明，CD12结合哺乳动物α-烯醇酶（ENO1），通过Hippo信号通路增强YAP1 （es-associated protein 1）蛋白水平，激活再生转录程序。表达CD12的工程益生菌复制了其治疗益处，提供了一种可翻译的递送策略。我们的工作扩大了真菌组的治疗潜力，将其定位为炎症性和医源性肠道疾病的生物制剂来源。
{"title":"Fungal commensal promotes intestinal repair via its secreted peptide in mice","authors":"Yiru Gao, Tengyu Wang, Nan Nan, Feng Tian, Lingchen Tan, Huining Yan, Xueqiang Peng, Shaoqin Zheng, Yan He, Haijiao Zhang, Hui Li, Qing Fan, Chenhao Suo, Wanli Zhang, Yafang Shi, Wei Du, Jincong Jiang, Hailong Li, Mingyu Zhang, Jiahui Wu, Haiyao Zhou, Yan Cheng, Yidi Nian, Xiao Wang, Xun Sun, Ren Sheng, Qianqian Zheng, Chen Ding","doi":"10.1038/s41564-025-02233-y","DOIUrl":"10.1038/s41564-025-02233-y","url":null,"abstract":"The intestinal epithelium relies on continuous stem cell-driven renewal to maintain barrier function and recover from injury. While bacterial signals are known to influence intestinal stem cell behaviour, the regenerative capacity of the gut mycobiome has remained largely unexplored. Here we identify the commensal fungus Kazachstania pintolopesii (Kp) as a critical mediator of intestinal regeneration through its secreted protein Ygp1. We found that a 12-amino acid peptide fragment of Ygp1, CD12, was sufficient to promote intestinal organoid differentiation and accelerate intestinal healing in murine models of colitis and chemotherapy-induced injury. Transcriptomics, simulations and molecular interaction experiments revealed that CD12 binds mammalian α-enolase (ENO1), enhancing YAP1 (Yes-associated protein 1) protein levels and activating regenerative transcriptional programmes through the Hippo signalling pathway. Engineered probiotics expressing CD12 replicated its therapeutic benefits, offering a translatable delivery strategy. Our work expands the therapeutic potential of the mycobiome, positioning it as a source of biologics for inflammatory and iatrogenic gut disorders. A short peptide derived from a commensal-fungal-secreted protein promotes repair in models of colon epithelial damage when delivered directly or via probiotic microbes.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"476-491"},"PeriodicalIF":19.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1038/s41564-025-02217-y
Alexander Jovanovic, Frederick K. Bright, Ahmad Sadeghi, Basil Wicki, Santiago E. Caño Muñiz, Greta C. Giannini, Sara Toprak, Loïc Sauteur, Anna Rodoni, Andreas Wüst, Andréanne Lupien, Sonia Borrell, Dorothy M. Grogono, Nicole E. Wheeler, Philippe Dehio, Johannes Nemeth, Hans Pargger, Rachel Thomson, Scott C. Bell, Sebastien Gagneux, Josephine M. Bryant, Tingying Peng, Andreas H. Diacon, R. Andres Floto, Michael Abanto, Lucas Boeck
In vitro antibiotic testing is important for guiding therapy and drug development. Current methods are focused on growth inhibition in bulk bacterial populations but often fail to accurately predict treatment responses. Here we introduce Antimicrobial Single-Cell Testing (ASCT), a large-scale live-cell imaging approach that quantifies bacterial killing in real time at single-cell resolution. By tracking over 140 million mycobacteria and analysing ~20,000 time–kill curves, we identify key determinants of antibiotic killing and its clinical relevance. For Mycobacterium tuberculosis, we found that drug-specific killing dynamics in starved bacteria, rather than growth inhibition or killing of growing cells, predict regimen efficacy in mice and humans. Extending this approach to Mycobacterium abscessus and comparing 405 bacterial strains, we show that antibiotic killing is also a genetically encoded bacterial trait (drug tolerance). We demonstrate that tolerance patterns cluster by antibiotic targets, identify a phage protein that modulates antibiotic killing, and show that strain-specific killing dynamics are associated with individual patient outcomes independent of drug resistance. Together, these findings establish a framework that reveals how drug properties and bacterial diversity shape treatment responses, offering a path to more effective and personalized therapies. Via high-throughput imaging and tracking over 140 million single mycobacteria, the authors show that drug- and strain-specific killing predict treatment outcomes, with potential to improve drug development and personalized therapy.
{"title":"Large-scale testing of antimicrobial lethality at single-cell resolution predicts mycobacterial infection outcomes","authors":"Alexander Jovanovic, Frederick K. Bright, Ahmad Sadeghi, Basil Wicki, Santiago E. Caño Muñiz, Greta C. Giannini, Sara Toprak, Loïc Sauteur, Anna Rodoni, Andreas Wüst, Andréanne Lupien, Sonia Borrell, Dorothy M. Grogono, Nicole E. Wheeler, Philippe Dehio, Johannes Nemeth, Hans Pargger, Rachel Thomson, Scott C. Bell, Sebastien Gagneux, Josephine M. Bryant, Tingying Peng, Andreas H. Diacon, R. Andres Floto, Michael Abanto, Lucas Boeck","doi":"10.1038/s41564-025-02217-y","DOIUrl":"10.1038/s41564-025-02217-y","url":null,"abstract":"In vitro antibiotic testing is important for guiding therapy and drug development. Current methods are focused on growth inhibition in bulk bacterial populations but often fail to accurately predict treatment responses. Here we introduce Antimicrobial Single-Cell Testing (ASCT), a large-scale live-cell imaging approach that quantifies bacterial killing in real time at single-cell resolution. By tracking over 140 million mycobacteria and analysing ~20,000 time–kill curves, we identify key determinants of antibiotic killing and its clinical relevance. For Mycobacterium tuberculosis, we found that drug-specific killing dynamics in starved bacteria, rather than growth inhibition or killing of growing cells, predict regimen efficacy in mice and humans. Extending this approach to Mycobacterium abscessus and comparing 405 bacterial strains, we show that antibiotic killing is also a genetically encoded bacterial trait (drug tolerance). We demonstrate that tolerance patterns cluster by antibiotic targets, identify a phage protein that modulates antibiotic killing, and show that strain-specific killing dynamics are associated with individual patient outcomes independent of drug resistance. Together, these findings establish a framework that reveals how drug properties and bacterial diversity shape treatment responses, offering a path to more effective and personalized therapies. Via high-throughput imaging and tracking over 140 million single mycobacteria, the authors show that drug- and strain-specific killing predict treatment outcomes, with potential to improve drug development and personalized therapy.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"566-583"},"PeriodicalIF":19.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02217-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-08DOI: 10.1038/s41564-025-02231-0
Maria Guedes, Simon Peters, Amruta Joshi, Sina Dorn, Janina Rieger, Kimberly Klapproth, Tristan Beste, Alexander M. Leipold, Mathias Rosenfeldt, Antoine-Emmanuel Saliba, Ulrich Dobrindt, Charis Kalogirou, Carmen Aguilar
Bacterial prostatitis caused by uropathogenic Escherichia coli (UPEC) strains is a highly prevalent and recurrent infection responsible for significant morbidity in men. The molecular pathogenesis of prostatitis remains poorly understood, partly due to a lack of suitable in vitro models. Here we developed a 2D mouse stem cell-derived prostate epithelial organoid model. In the organoid model, 5α-dihydrotestosterone promoted differentiation of basal into luminal cells, while transcriptomic analyses validated the model in comparison to 3D models and mouse prostate tissue. Infection analyses revealed that UPEC preferentially attached to, invaded and replicated within luminal prostate cells. Experiments with a UPEC mutant strain lacking the bacterial adhesin, FimH, alongside immunoprecipitation, mass spectrometry, biochemistry and infection experiments with host gene knockouts revealed that FimH–prostatic acid phosphatase (PPAP) binding interactions promote UPEC invasion of luminal prostate cells. ᴅ-Mannose competitively inhibited FimH–PPAP interactions. Findings were validated using ex vivo human prostate tissue. These data highlight the adaptability of FimH in engaging host receptors and the potential for FimH-targeting strategies to reduce bacterial prostatitis. Uropathogenic Escherichia coli infection of a murine prostate organoid model reveals a bacterial FimH–host prostatic acid phosphatase adhesin-receptor interaction enabling invasion and replication within the host tissue.
{"title":"Uropathogenic Escherichia coli invade luminal prostate cells via FimH–PPAP receptor binding","authors":"Maria Guedes, Simon Peters, Amruta Joshi, Sina Dorn, Janina Rieger, Kimberly Klapproth, Tristan Beste, Alexander M. Leipold, Mathias Rosenfeldt, Antoine-Emmanuel Saliba, Ulrich Dobrindt, Charis Kalogirou, Carmen Aguilar","doi":"10.1038/s41564-025-02231-0","DOIUrl":"10.1038/s41564-025-02231-0","url":null,"abstract":"Bacterial prostatitis caused by uropathogenic Escherichia coli (UPEC) strains is a highly prevalent and recurrent infection responsible for significant morbidity in men. The molecular pathogenesis of prostatitis remains poorly understood, partly due to a lack of suitable in vitro models. Here we developed a 2D mouse stem cell-derived prostate epithelial organoid model. In the organoid model, 5α-dihydrotestosterone promoted differentiation of basal into luminal cells, while transcriptomic analyses validated the model in comparison to 3D models and mouse prostate tissue. Infection analyses revealed that UPEC preferentially attached to, invaded and replicated within luminal prostate cells. Experiments with a UPEC mutant strain lacking the bacterial adhesin, FimH, alongside immunoprecipitation, mass spectrometry, biochemistry and infection experiments with host gene knockouts revealed that FimH–prostatic acid phosphatase (PPAP) binding interactions promote UPEC invasion of luminal prostate cells. ᴅ-Mannose competitively inhibited FimH–PPAP interactions. Findings were validated using ex vivo human prostate tissue. These data highlight the adaptability of FimH in engaging host receptors and the potential for FimH-targeting strategies to reduce bacterial prostatitis. Uropathogenic Escherichia coli infection of a murine prostate organoid model reveals a bacterial FimH–host prostatic acid phosphatase adhesin-receptor interaction enabling invasion and replication within the host tissue.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"535-550"},"PeriodicalIF":19.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02231-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-08DOI: 10.1038/s41564-025-02225-y
Cynthia L. Hsu, Shikha Shukla, Linton Freund, Annie C. Chou, Yongqiang Yang, Ryan Bruellman, Fernanda Raya Tonetti, Noemí Cabré, Susan Mayo, Hyun Gyu Lim, Valeria Magallan, Barbara J. Cordell, Sonja Lang, Münevver Demir, Peter Stärkel, Cristina Llorente, Bernhard O. Palsson, Chitra Mandyam, Brigid S. Boland, Elizabeth Hohmann, Bernd Schnabl
Auto-brewery syndrome (ABS) is a rarely diagnosed disorder of alcohol intoxication due to gut microbial ethanol production. Despite case reports and a small cohort study, the microbiological profiles of patients remain poorly understood. Here we conducted an observational study of 22 patients with ABS and 21 unaffected household partners. Faecal samples from individuals with ABS during a flare produced more ethanol in vitro, which could be reduced by antibiotic treatment. Gut microbiome analysis using metagenomics revealed an enrichment of Proteobacteria, including Escherichia coli and Klebsiella pneumoniae. Genes in metabolic pathways associated with ethanol production were enriched, including the mixed-acid fermentation pathway, heterolactic fermentation pathway and ethanolamine utilization pathway. Faecal metabolomics revealed increased acetate levels associated with ABS, which correlated with blood alcohol concentrations. Finally, one patient was treated with faecal microbiota transplantation, with positive correlations between gut microbiota composition and function, and symptoms. These findings can inform future clinical interventions for ABS. Gut microorganisms capable of producing ethanol cause alcohol intoxication, which can be corrected via faecal microbiota transplantation.
{"title":"Gut microbial ethanol metabolism contributes to auto-brewery syndrome in an observational cohort","authors":"Cynthia L. Hsu, Shikha Shukla, Linton Freund, Annie C. Chou, Yongqiang Yang, Ryan Bruellman, Fernanda Raya Tonetti, Noemí Cabré, Susan Mayo, Hyun Gyu Lim, Valeria Magallan, Barbara J. Cordell, Sonja Lang, Münevver Demir, Peter Stärkel, Cristina Llorente, Bernhard O. Palsson, Chitra Mandyam, Brigid S. Boland, Elizabeth Hohmann, Bernd Schnabl","doi":"10.1038/s41564-025-02225-y","DOIUrl":"10.1038/s41564-025-02225-y","url":null,"abstract":"Auto-brewery syndrome (ABS) is a rarely diagnosed disorder of alcohol intoxication due to gut microbial ethanol production. Despite case reports and a small cohort study, the microbiological profiles of patients remain poorly understood. Here we conducted an observational study of 22 patients with ABS and 21 unaffected household partners. Faecal samples from individuals with ABS during a flare produced more ethanol in vitro, which could be reduced by antibiotic treatment. Gut microbiome analysis using metagenomics revealed an enrichment of Proteobacteria, including Escherichia coli and Klebsiella pneumoniae. Genes in metabolic pathways associated with ethanol production were enriched, including the mixed-acid fermentation pathway, heterolactic fermentation pathway and ethanolamine utilization pathway. Faecal metabolomics revealed increased acetate levels associated with ABS, which correlated with blood alcohol concentrations. Finally, one patient was treated with faecal microbiota transplantation, with positive correlations between gut microbiota composition and function, and symptoms. These findings can inform future clinical interventions for ABS. Gut microorganisms capable of producing ethanol cause alcohol intoxication, which can be corrected via faecal microbiota transplantation.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 2","pages":"415-428"},"PeriodicalIF":19.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-07DOI: 10.1038/s41564-025-02214-1
Bernhard O. Palsson, Sang Yup Lee, Gi Bae Kim
Although genome sequencing technologies have advanced rapidly, microbial genomes still contain numerous genes with unknown functions, posing ongoing challenges for comprehensive genome annotation. Traditional annotation methods are constrained by a lack of scalable experimental techniques and the limitations of conventional homology-based computational approaches. Recent computational innovations, particularly deep learning, have substantially improved gene function prediction, facilitating more efficient annotation of transcription factors, enzymes and other protein classes. Integrating computational and experimental approaches has enabled the development of workflows that systematize gene function discovery, paving the way for faster, more accurate and comprehensive genome annotation. Continued refinement of these integrated methods holds great promise for deepening our understanding of microorganisms. Here we review recent advances in artificial intelligence for gene function discovery and discuss future directions for achieving interpretable and high-throughput artificial intelligence-guided annotation. In this Review, the authors discuss how artificial intelligence can aid microbial gene function discovery.
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Pub Date : 2026-01-05DOI: 10.1038/s41564-025-02227-w
Michail S. Lionakis
IL-17 modulates fungal fitness to maintain Candida albicans in a less pathogenic state within the oral mucosa.
IL-17调节真菌适应度以维持口腔黏膜内白色念珠菌处于较低致病性状态。
{"title":"Taming Candida with IL-17","authors":"Michail S. Lionakis","doi":"10.1038/s41564-025-02227-w","DOIUrl":"10.1038/s41564-025-02227-w","url":null,"abstract":"IL-17 modulates fungal fitness to maintain Candida albicans in a less pathogenic state within the oral mucosa.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"14-15"},"PeriodicalIF":19.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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