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Contaminated drinking water facilitates Escherichia coli strain-sharing within households in urban informal settlements 受污染的饮用水促进了城市非正式住区家庭内大肠杆菌菌株的共享
IF 28.3 1区 生物学
Nature Microbiology Pub Date : 2025-05-01 DOI: 10.1038/s41564-025-01986-w
Daehyun D. Kim, Jenna M. Swarthout, Colin J. Worby, Benard Chieng, John Mboya, Ashlee M. Earl, Sammy M. Njenga, Amy J. Pickering
{"title":"Contaminated drinking water facilitates Escherichia coli strain-sharing within households in urban informal settlements","authors":"Daehyun D. Kim, Jenna M. Swarthout, Colin J. Worby, Benard Chieng, John Mboya, Ashlee M. Earl, Sammy M. Njenga, Amy J. Pickering","doi":"10.1038/s41564-025-01986-w","DOIUrl":"https://doi.org/10.1038/s41564-025-01986-w","url":null,"abstract":"<p>Identifying bacterial transmission pathways is crucial to inform strategies that limit the spread of pathogenic and antibiotic-resistant bacteria. Here we assessed <i>Escherichia coli</i> strain-sharing and overlap of antibiotic resistance genes (ARGs) across humans, poultry, canines, soil, and drinking water within and between households in urban informal settlements in Nairobi, Kenya. We collected 321 samples from 50 households with half having access to chlorinated water. We performed Pooling Isolated Colonies-seq, which sequences pools of up to five <i>E. coli</i> colonies per sample to capture strain diversity. Pooling Isolated Colonies-seq captured 1,516 colonies and identified 154 strain-sharing events, overcoming limitations of single-isolate sequencing and metagenomics. Within households, strain-sharing rates and resistome similarities across sample types were strongly correlated, suggesting clonal transmission of ARGs. <i>E. coli</i> isolated from the environment carried clinically relevant ARGs. Strain-sharing was rare between animals and humans but frequent between humans and drinking water. <i>E. coli</i>-contaminated stored drinking water was associated with higher human–human strain-sharing within households. These results suggest that contaminated drinking water facilitates human to human strain-sharing, and water treatment can disrupt transmission.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"223 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893448","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
Engineered orthogonal and obligate bacterial commensalism mediated by a non-standard amino acid 由非标准氨基酸介导的工程正交和专性细菌共生
IF 28.3 1区 生物学
Nature Microbiology Pub Date : 2025-05-01 DOI: 10.1038/s41564-025-01999-5
Amanda M. Forti, Michaela A. Jones, Defne N. Elbeyli, Neil D. Butler, Aditya M. Kunjapur
{"title":"Engineered orthogonal and obligate bacterial commensalism mediated by a non-standard amino acid","authors":"Amanda M. Forti, Michaela A. Jones, Defne N. Elbeyli, Neil D. Butler, Aditya M. Kunjapur","doi":"10.1038/s41564-025-01999-5","DOIUrl":"https://doi.org/10.1038/s41564-025-01999-5","url":null,"abstract":"<p>Microorganisms can be genetically engineered for intrinsic biological containment based on synthetic chemical provision. However, reliance on an exogenous chemical limits the contexts where a contained microorganism could survive. Here we design an orthogonal obligate commensalism in <i>Escherichia coli</i> that autonomously creates environments permissive for survival of a partner microbe. We engineer one <i>E. coli</i> strain (the producer) to biosynthesize a non-standard amino acid (nsAA) from simple carbon sources through heterologous expression. We engineer a second <i>E. coli</i> strain (the utilizer) to rely on the same nsAA for growth as a synthetic auxotroph, with a 14-day escape rate of 2.8 × 10<sup>−9</sup> escapees per colony-forming unit. Co-culture experiments show utilizer dependence on the producer, with no escape detected during co-inoculation of ~10<sup>7</sup> colony-forming units of utilizer and a non-producer <i>E. coli</i> strain. Dependence is maintained within a simplified synthetic maize root-associated community. This work provides ecological insights and presents a potential biocontainment strategy independent of an exogenous chemical.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893447","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
MAVS is a sensor of fumarate during antiviral immunity MAVS是抗病毒免疫过程中富马酸盐的传感器
IF 28.3 1区 生物学
Nature Microbiology Pub Date : 2025-04-23 DOI: 10.1038/s41564-025-01991-z
Yukun Min, Luke A. J. O’Neill
{"title":"MAVS is a sensor of fumarate during antiviral immunity","authors":"Yukun Min, Luke A. J. O’Neill","doi":"10.1038/s41564-025-01991-z","DOIUrl":"https://doi.org/10.1038/s41564-025-01991-z","url":null,"abstract":"Viral infection of macrophages causes metabolic rewiring, increasing the level of cytosolic fumarate owing to increased argininosuccinate synthase 1 expression. Fumarate succinates mitochondrial antiviral-signalling protein, promoting its ability to drive type I interferon production and antiviral immunity.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"91 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862089","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
Communicating the promise of phage therapy 传达噬菌体治疗的前景
IF 28.3 1区 生物学
Nature Microbiology Pub Date : 2025-04-23 DOI: 10.1038/s41564-025-01992-y
Sabrina Green
{"title":"Communicating the promise of phage therapy","authors":"Sabrina Green","doi":"10.1038/s41564-025-01992-y","DOIUrl":"https://doi.org/10.1038/s41564-025-01992-y","url":null,"abstract":"Use social media, talks, blogs and podcasts to raise awareness about antimicrobial resistance and push for wider access to life-saving phage treatments, writes Sabrina Green.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"65 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862092","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
Linking bacterial androgen production and prostate cancer 细菌雄激素产生与前列腺癌之间的联系
IF 28.3 1区 生物学
Nature Microbiology Pub Date : 2025-04-21 DOI: 10.1038/s41564-025-01996-8
Gabriela Arp, Sophia Levy, Brantley Hall
{"title":"Linking bacterial androgen production and prostate cancer","authors":"Gabriela Arp, Sophia Levy, Brantley Hall","doi":"10.1038/s41564-025-01996-8","DOIUrl":"https://doi.org/10.1038/s41564-025-01996-8","url":null,"abstract":"Commensal bacteria, including those isolated from urinary tract and prostate tissues, encode enzymes to convert androstenedione to epitestosterone, expanding our knowledge of microbial steroid metabolism and suggesting potential links to prostate cancer and treatment efficacy.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"1 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853180","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
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":"<p>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 <i>Clostridium scindens</i> and named this gene <i>desF</i>. We demonstrate that epitestosterone impacts androgen receptor-dependent prostate cancer cell proliferation in vitro. We also demonstrate that stool <i>desF</i> 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 <i>desG</i> gene was detected in strains of the urinary tract bacterium <i>Propionimicrobium lymphophilum</i>. 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.</p>","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":"<p>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.</p>","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":"<p>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 <i>Plesiomonas</i> strain, but not a human-derived <i>E. coli</i>, 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.</p>","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
{"title":"Extract to lyse bacterial pathogens","authors":"Mahyar Aghapour, Lina Herhaus","doi":"10.1038/s41564-025-01995-9","DOIUrl":"https://doi.org/10.1038/s41564-025-01995-9","url":null,"abstract":"The AAA-ATPase, p97, binds ubiquitinated bacterial surface proteins, extracting them with a mechanical force that disrupts and lyses the bacterial cell envelope. Thus, ubiquitination and proteasomal targeting provide cell autonomous immunity against cytosolic intracellular pathogens.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"8 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846647","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
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":"<p>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.</p>","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
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