Nature Microbiology最新文献_第2页

An expanded metabolic pathway for androgen production by commensal bacteria 共生细菌产生雄激素的扩展代谢途径

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-04-21 DOI: 10.1038/s41564-025-01979-9

Taojun Wang, Saeed Ahmad, Angélica Cruz-Lebrón, Sarah E. Ernst, Kelly Yovani Olivos Caicedo, Yoon Jeong, Briawna Binion, Pauline Mbuvi, Debapriya Dutta, Francelys V. Fernandez-Materan, Adam M. Breister, Elizabeth Tang, Jae Won Lee, Jason D. Kang, Spencer C. Harris, Shigeo Ikegawa, H. Rex Gaskins, John W. Erdman, Glen Yang, Isaac Cann, Steven L. Daniel, Phillip B. Hylemon, Karthik Anantharaman, Rafael C. Bernardi, João M. P. Alves, Karen S. Sfanos, Joseph Irudayaraj, Jason M. Ridlon

{"title":"An expanded metabolic pathway for androgen production by commensal bacteria","authors":"Taojun Wang, Saeed Ahmad, Angélica Cruz-Lebrón, Sarah E. Ernst, Kelly Yovani Olivos Caicedo, Yoon Jeong, Briawna Binion, Pauline Mbuvi, Debapriya Dutta, Francelys V. Fernandez-Materan, Adam M. Breister, Elizabeth Tang, Jae Won Lee, Jason D. Kang, Spencer C. Harris, Shigeo Ikegawa, H. Rex Gaskins, John W. Erdman, Glen Yang, Isaac Cann, Steven L. Daniel, Phillip B. Hylemon, Karthik Anantharaman, Rafael C. Bernardi, João M. P. Alves, Karen S. Sfanos, Joseph Irudayaraj, Jason M. Ridlon","doi":"10.1038/s41564-025-01979-9","DOIUrl":"https://doi.org/10.1038/s41564-025-01979-9","url":null,"abstract":"Commensal bacteria have been implicated in the modulation of steroid hormones, including circulating androgen levels in the host. However, the microbial genetic pathways involved in androgen production have not been fully characterized. Here we identify a microbial gene encoding an enzyme that catalyses the conversion of androstenedione to epitestosterone in the gut microbiome member Clostridium scindens and named this gene desF. We demonstrate that epitestosterone impacts androgen receptor-dependent prostate cancer cell proliferation in vitro. We also demonstrate that stool desF levels are elevated in patients with prostate cancer who are unresponsive to abiraterone/prednisone therapy. Bacterial isolates from urine or prostatectomy tissue produced androgens, and 17β-hydroxysteroid dehydrogenase activity encoded by the desG gene was detected in strains of the urinary tract bacterium Propionimicrobium lymphophilum. Furthermore, we demonstrate that urinary androgen-producing bacterial strains can promote prostate cancer cell growth through metabolism of cortisol and prednisone. Abiraterone, which targets host desmolase (CYP17A1), a rate-limiting enzyme in adrenal steroidogenesis, does not inhibit bacterial desmolase (DesAB), whereas the conversion of prednisone to androgens by DesAB, DesF and DesG drives androgen-receptor-dependent prostate cancer cell line proliferation in vitro. Our results are a significant advance in steroid microbiology and highlight a potentially important role for gut and urinary tract bacteria in host endocrine function and drug metabolism.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"125 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853183","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}

引用次数: 0

Metabolic remodelling produces fumarate via the aspartate–argininosuccinate shunt in macrophages as an antiviral defence 代谢重塑通过巨噬细胞中的天冬氨酸-精氨酸琥珀酸分流产生富马酸作为抗病毒防御

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-04-18 DOI: 10.1038/s41564-025-01985-x

Wenjun Xia, Youxiang Mao, Ziyan Xia, Jie Cheng, Peng Jiang

{"title":"Metabolic remodelling produces fumarate via the aspartate–argininosuccinate shunt in macrophages as an antiviral defence","authors":"Wenjun Xia, Youxiang Mao, Ziyan Xia, Jie Cheng, Peng Jiang","doi":"10.1038/s41564-025-01985-x","DOIUrl":"https://doi.org/10.1038/s41564-025-01985-x","url":null,"abstract":"Metabolic remodelling underpins macrophage effector functions in response to various stimuli, but the mechanisms involved are unclear. Here we report that viral-infection-induced inflammatory stimulation causes a rewiring of the urea cycle and the tricarboxylic acid cycle metabolism in macrophages to form a cyclic pathway called the aspartate–argininosuccinate (AAS) shunt. Using RNA sequencing, unbiased metabolomics and stable isotope tracing, we found that fumarate generated from the AAS shunt is driven by argininosuccinate synthase (ASS1) in the cytosol and potentiates inflammatory effects. Genetic ablation of ASS1 reduces intracellular fumarate levels and interferon-β production, and mitochondrial respiration is also suppressed. Notably, viral challenge or fumarate esters enhance interferon-β production via direct succination of the mitochondrial antiviral signalling protein and activation of the retinoic acid-inducible gene-I-like receptor signalling. In addition to the vesicular stomatitis virus, the Sendai virus and influenza A virus can also exert these effects. In addition, patients with Ebola virus disease have increased ASS1 expression and ASS1-deficient mice show suppressed macrophage interferon responses to vesicular stomatitis virus infection. These findings reveal that fumarate can be produced from the viral inflammation-induced AAS shunt and is essential for antiviral innate immunity.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"40 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846440","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}

引用次数: 0

Phollow reveals in situ phage transmission dynamics in the zebrafish gut microbiome at single-virion resolution 以下揭示了斑马鱼肠道微生物群中单病毒粒子分辨率下的原位噬菌体传播动力学

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-04-18 DOI: 10.1038/s41564-025-01981-1

Lizett Ortiz de Ora, Elizabeth T. Wiles, Mirjam Zünd, Maria S. Bañuelos, Nancy Haro-Ramirez, Diana S. Suder, Naveena Ujagar, Julio Ayala-Angulo, Calvin Trinh, Courtney Knitter, Shane Gonen, Dequina A. Nicholas, Travis J. Wiles

{"title":"Phollow reveals in situ phage transmission dynamics in the zebrafish gut microbiome at single-virion resolution","authors":"Lizett Ortiz de Ora, Elizabeth T. Wiles, Mirjam Zünd, Maria S. Bañuelos, Nancy Haro-Ramirez, Diana S. Suder, Naveena Ujagar, Julio Ayala-Angulo, Calvin Trinh, Courtney Knitter, Shane Gonen, Dequina A. Nicholas, Travis J. Wiles","doi":"10.1038/s41564-025-01981-1","DOIUrl":"https://doi.org/10.1038/s41564-025-01981-1","url":null,"abstract":"Bacteriophages show promise for microbiome engineering, but studying their transmission dynamics in multimember communities and animal hosts is technically challenging. We therefore created ‘Phollow’, a live imaging-based approach for tracking phage replication and spread in situ with single-virion resolution. Following interbacterial phage transmission is achieved by marking virions with distinct fluorescent proteins during assembly in newly infected cells. In vitro cell virology studies revealed clouds of phage virions dispersing upon bacterial lysis, leading to rampant transmission. Combining Phollow with optically transparent zebrafish, we visualized phage outbreaks within the vertebrate gut. We observed that virions from a zebrafish-derived Plesiomonas strain, but not a human-derived E. coli, rapidly disseminate systemically to the liver and brain. Moreover, antibiotics triggered waves of interbacterial transmission and sudden shifts in gut community ecology. Phollow ultimately empowers multiscale investigations of phage transmission and transkingdom interactions that have the potential to open new avenues for phage-based microbiome therapies.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"24 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846441","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}

引用次数: 0

Extract to lyse bacterial pathogens 提取物裂解细菌病原体

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-04-18 DOI: 10.1038/s41564-025-01995-9

Mahyar Aghapour, Lina Herhaus

引用次数: 0

Dairy cows develop protective immunity against reinfection with bovine H5N1 influenza virus 奶牛对牛H5N1流感病毒的再感染产生保护性免疫

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-04-17 DOI: 10.1038/s41564-025-01998-6

Antonio Facciuolo, Lauren Aubrey, Ulises Barron-Castillo, Nathalie Berube, Carla Norleen, Shannon McCreary, Yanyun Huang, Natalia Pessoa, Leslie Macas Jacome, Samira Mubareka, Allison McGeer, Yohannes Berhane, Volker Gerdts, Andrew Van Kessel, Bryce Warner, Yan Zhou

{"title":"Dairy cows develop protective immunity against reinfection with bovine H5N1 influenza virus","authors":"Antonio Facciuolo, Lauren Aubrey, Ulises Barron-Castillo, Nathalie Berube, Carla Norleen, Shannon McCreary, Yanyun Huang, Natalia Pessoa, Leslie Macas Jacome, Samira Mubareka, Allison McGeer, Yohannes Berhane, Volker Gerdts, Andrew Van Kessel, Bryce Warner, Yan Zhou","doi":"10.1038/s41564-025-01998-6","DOIUrl":"https://doi.org/10.1038/s41564-025-01998-6","url":null,"abstract":"Infection of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in dairy cows causes severe mastitis and milk production losses. Whether cows can develop protective immunity is unclear. Here we infected three lactating cows with HPAI H5N1 genotype B3.13 via the hindquarters of the udder to mimic intra-mammary infection. Inoculated cows displayed clinical responses consistent with affected dairy herds in the United States including virus shedding almost exclusively in inoculated hindquarters that peaked between Days 2–4 post inoculation and gradually declined by Day 21. Histologically, peak virus shedding in milk corresponded with severe acute necrotic mastitis in the inoculated hindquarters but not in the uninoculated forequarters. Two cows were reinfected with HPAI H5N1 virus at unaffected forequarters following resolution of infection. Secondary inoculation did not result in clinical manifestations or virus shedding in milk. Virus-neutralizing antibodies were detected at Day 14 post inoculation in milk with higher titres observed in the inoculated hindquarters relative to the forequarters. We also detected HPAI H5N1 viral RNA in air samples from animal rooms during routine husbandry activity. These data indicate that primary infection via intra-mammary inoculation can generate protective immunity against bovine HPAI H5N1 virus in dairy cows.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"26 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841322","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}

引用次数: 0

Microbial oxidation of short-chain gaseous alkanes 短链气态烷烃的微生物氧化作用

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-04-15 DOI: 10.1038/s41564-025-01982-0

Mengxiong Wu, Xiawei Liu, Florin Musat, Jianhua Guo

引用次数: 0

The T-series bacteriophages are reductionist models that continue to shape the field t系列噬菌体是继续塑造该领域的还原论模型

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-04-14 DOI: 10.1038/s41564-025-01990-0

Jeremy J. Barr

引用次数: 0

Host AAA-ATPase VCP/p97 lyses ubiquitinated intracellular bacteria as an innate antimicrobial defence 宿主aaa - atp酶VCP/p97裂解泛素化细胞内细菌作为先天抗菌防御

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-04-11 DOI: 10.1038/s41564-025-01984-y

Sourav Ghosh, Suvapriya Roy, Navin Baid, Udit Kumar Das, Sumit Rakshit, Paulomi Sanghavi, Dipasree Hajra, Sayani Das, Sneha Menon, Mohammad Sahil, Sudipti Shaw, Raju S. Rajmani, Harikrishna Adicherla, Sandip Kaledhonkar, Jagannath Mondal, Dipshikha Chakravortty, Roop Mallik, Anirban Banerjee

{"title":"Host AAA-ATPase VCP/p97 lyses ubiquitinated intracellular bacteria as an innate antimicrobial defence","authors":"Sourav Ghosh, Suvapriya Roy, Navin Baid, Udit Kumar Das, Sumit Rakshit, Paulomi Sanghavi, Dipasree Hajra, Sayani Das, Sneha Menon, Mohammad Sahil, Sudipti Shaw, Raju S. Rajmani, Harikrishna Adicherla, Sandip Kaledhonkar, Jagannath Mondal, Dipshikha Chakravortty, Roop Mallik, Anirban Banerjee","doi":"10.1038/s41564-025-01984-y","DOIUrl":"https://doi.org/10.1038/s41564-025-01984-y","url":null,"abstract":"Cell-autonomous immunity prevents intracellular pathogen growth through mechanisms such as ubiquitination and proteasomal targeting of bacteria for degradation. However, how the proteasome eradicates ubiquitinated bacteria has remained unclear. Here we show that host AAA-ATPase, VCP/p97, associates with diverse cytosol-exposed ubiquitinated bacteria (Streptococcus pneumoniae, Salmonella enterica serovar Typhimurium, Streptococcus pyogenes) and requires the ATPase activity in its D2 domain to reduce intracellular bacterial loads. Combining optical trap approaches along with molecular dynamic simulations, in vitro reconstitution and immunogold transmission electron microscopy, we demonstrate that p97 applies mechanical force to extract ubiquitinated surface proteins, BgaA and PspA, from S. pneumoniae cell membranes. This causes extensive membrane lysis and release of cytosolic content, thereby killing the pathogen. Further, p97 also controls S. pneumoniae proliferation in mice, ultimately protecting from fatal sepsis. Overall, we discovered a distinct innate antimicrobial function of p97 that can protect the host against lethal bacterial infections.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"17 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819359","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}

引用次数: 0

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-04-11 DOI: 10.1038/s41564-025-01980-2

Belen Pachano, Dayana C. Farhat, Martina Shahinas, Jill von Velsen, Charlotte Corrao, Lucid Belmudes, Pieter-Jan de Bock, Caroline Mas, Yohann Couté, Matthew W. Bowler, Alexandre Bougdour, Christopher Swale, Mohamed-Ali Hakimi

{"title":"An ISWI-related chromatin remodeller regulates stage-specific gene expression in Toxoplasma gondii","authors":"Belen Pachano, Dayana C. Farhat, Martina Shahinas, Jill von Velsen, Charlotte Corrao, Lucid Belmudes, Pieter-Jan de Bock, Caroline Mas, Yohann Couté, Matthew W. Bowler, Alexandre Bougdour, Christopher Swale, Mohamed-Ali Hakimi","doi":"10.1038/s41564-025-01980-2","DOIUrl":"https://doi.org/10.1038/s41564-025-01980-2","url":null,"abstract":"ATP-dependent chromatin remodellers are specialized multiprotein machines that organize the genome in eukaryotic cells and regulate its accessibility by repositioning, ejecting or modifying nucleosomes. However, their role in Toxoplasma gondii is poorly understood. Here we show that T. gondii has evolved two divergent proteins within the imitation switch (ISWI) family: TgSNF2h and TgSNF2L. TgSNF2h specifically forms a core complex with the transcription factor AP2VIII-2 and the scaffold protein TgRFTS. Depletion of TgRFTS phenocopies the knockdown of TgSNF2h, restricting access to chromatin and altering local gene expression. At the genomic level, TgSNF2h insulates highly transcribed genes from silenced neighbours, ensuring stage-specific gene regulation. By modulating chromatin accessibility to transcription factors, TgSNF2h exerts epistatic control over MORC, a key regulator of sexual commitment. Our findings show that a specific ISWI complex orchestrates the partitioning of developmental genes and ensures transcriptional fidelity throughout the parasite life cycle.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"12 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819360","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}

引用次数: 0

Moving from genome-scale to community-scale metabolic models for the human gut microbiome 从基因组尺度到群落尺度的人类肠道微生物群代谢模型

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-04-11 DOI: 10.1038/s41564-025-01972-2

Nick Quinn-Bohmann, Alex V. Carr, Christian Diener, Sean M. Gibbons

引用次数: 0