Nature Microbiology最新文献

{"title":"The challenges of treating severe A(H5N1) influenza","authors":"","doi":"10.1038/s41564-025-01974-0","DOIUrl":"10.1038/s41564-025-01974-0","url":null,"abstract":"Our study assessed the ability of existing influenza antivirals to treat severe A(H5N1) influenza in a mouse model. Results were dependent on drug, dosage and infection route but highlighted the need to explore further options for treatment.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 4","pages":"823-824"},"PeriodicalIF":20.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758172","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}

{"title":"Colonic goblet cell-associated antigen passages mediate physiologic and beneficial translocation of live gut bacteria in preweaning mice","authors":"Sreeram Udayan, Alexandria N. Floyd, Vini John, Bibiana E. Barrios, Brigida A. Rusconi, Keely G. McDonald, Ellen Merrick Schill, Devesha H. Kulkarni, Andrew L. Martin, Rafael Gutierrez, Khushi B. Talati, Dalia L. Harris, Sushma Sundas, Kayla M. Burgess, Jocelyn T. Pauta, Elisabeth L. Joyce, Jacqueline D. Wang, Leslie D. Wilson, Kathryn A. Knoop, Phillip I. Tarr, Chyi-Song Hsieh, Rodney D. Newberry","doi":"10.1038/s41564-025-01965-1","DOIUrl":"10.1038/s41564-025-01965-1","url":null,"abstract":"Gut-resident microorganisms have time-limited effects in distant tissues during early life. However, the reasons behind this phenomenon are largely unknown. Here, using bacterial culture techniques, we show that a subset of live gut-resident bacteria translocate and disseminate to extraintestinal tissues (mesenteric lymph nodes and spleen) in preweaning (day of life 17), but not adult (day of life 35), mice. Translocation and dissemination in preweaning mice appeared physiologic as it did not induce an inflammatory response and required host goblet cells, the formation of goblet cell-associated antigen passages, sphingosine-1-phosphate receptor-dependent leukocyte trafficking and phagocytic cells. One translocating strain, Lactobacillus animalisWU, showed antimicrobial activity against the late-onset sepsis pathogen Escherichia coli ST69 in vitro, and its translocation was associated with protection from systemic sepsis in vivo. While limited in context, these findings challenge the idea that translocation of gut microbiota is pathological and show physiologic and beneficial translocation during early life. Colonic goblet cell-associated passages allow translocation of live bacteria to other organs in early life, potentially leading to beneficial impacts.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 4","pages":"927-938"},"PeriodicalIF":20.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744901","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}

{"title":"Parasite and vector circadian clocks mediate efficient malaria transmission","authors":"Inês Bento, Brianna A. Parrington, Rushlenne Pascual, Alexander S. Goldberg, Eileen Wang, Hani Liu, Helene Borrmann, Mira Zelle, Nicholas Coburn, Joseph S. Takahashi, Joshua E. Elias, Maria M. Mota, Filipa Rijo-Ferreira","doi":"10.1038/s41564-025-01949-1","DOIUrl":"10.1038/s41564-025-01949-1","url":null,"abstract":"Malaria transmission begins when Anopheles mosquitos deposit saliva and Plasmodium parasites during a bloodmeal. As Anopheles mosquitos are nocturnal, we investigated whether their salivary glands are under circadian control, anticipating bloodmeals and modulating parasite biology for host encounters. Here we show that approximately half of the mosquito salivary gland transcriptome, particularly genes essential for efficient bloodmeals such as anti-blood clotting factors, exhibits circadian expression. Furthermore, measuring haemoglobin levels, we demonstrate that mosquitos prefer to feed and ingest more blood at nighttime. Notably, we show a substantial subset of the salivary-gland-resident parasite transcriptome cycling throughout the day, indicating that this stage is not transcriptionally quiescent. Among the sporozoite genes undergoing rhythmic expression are those involved in parasite motility, potentially modulating the ability to initiate infection at different times of day. Our findings suggest a circadian tripartite relationship between the vector, parasite and mammalian host that together modulates malaria transmission. Mosquito salivary glands and malaria parasites exhibit daily rhythms, which impact blood feeding and sporozoite gene expression.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 4","pages":"882-896"},"PeriodicalIF":20.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-025-01949-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736574","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}

{"title":"Gut metagenomes reveal interactions between dietary restriction, ageing and the microbiome in genetically diverse mice","authors":"Lev Litichevskiy, Maya Considine, Jasleen Gill, Vasuprada Shandar, Timothy O. Cox, Hélène C. Descamps, Kevin M. Wright, Kevin R. Amses, Lenka Dohnalová, Megan J. Liou, Monika Tetlak, Mario R. Galindo-Fiallos, Andrea C. Wong, Patrick Lundgren, Junwon Kim, Giulia T. Uhr, Ryan J. Rahman, Sydney Mason, Carter Merenstein, Frederic D. Bushman, Anil Raj, Fiona Harding, Zhenghao Chen, G. V. Prateek, Martin Mullis, Andrew G. Deighan, Laura Robinson, Ceylan Tanes, Kyle Bittinger, Meenakshi Chakraborty, Ami S. Bhatt, Hongzhe Li, Ian Barnett, Emily R. Davenport, Karl W. Broman, Maayan Levy, Robert L. Cohen, David Botstein, Adam Freund, Andrea Di Francesco, Gary A. Churchill, Mingyao Li, Christoph A. Thaiss","doi":"10.1038/s41564-025-01963-3","DOIUrl":"https://doi.org/10.1038/s41564-025-01963-3","url":null,"abstract":"<p>The gut microbiome changes with age and has been proposed to mediate the benefit of lifespan-extending interventions such as dietary restriction. However, the causes and consequences of microbiome ageing and the potential of such interventions remain unclear. Here we analysed 2,997 metagenomes collected longitudinally from 913 deeply phenotyped, genetically diverse mice to investigate interactions between the microbiome, ageing, dietary restriction (caloric restriction and fasting), host genetics and a range of health parameters. Among the numerous age-associated microbiome changes that we find in this cohort, increased microbiome uniqueness is the most consistent parameter across a second longitudinal mouse experiment that we performed on inbred mice and a compendium of 4,101 human metagenomes. Furthermore, cohousing experiments show that age-associated microbiome changes may be caused by an accumulation of stochastic environmental exposures (neutral theory) rather than by the influence of an ageing host (selection theory). Unexpectedly, the majority of taxonomic and functional microbiome features show small but significant heritability, and the amount of variation explained by host genetics is similar to ageing and dietary restriction. We also find that more intense dietary interventions lead to larger microbiome changes and that dietary restriction does not rejuvenate the microbiome. Lastly, we find that the microbiome is associated with multiple health parameters, including body composition, immune components and frailty, but not lifespan. Overall, this study sheds light on the factors influencing microbiome ageing and aspects of host physiology modulated by the microbiome.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"222 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736576","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}

{"title":"ERK pathway reactivation prevents anthrax toxin lethality in mice","authors":"Jie Liu, Zehua Zuo, Michael Ewing, Qing Cao, Liu Cao, Qi Li, Toren Finkel, Stephen H. Leppla, Shihui Liu","doi":"10.1038/s41564-025-01977-x","DOIUrl":"https://doi.org/10.1038/s41564-025-01977-x","url":null,"abstract":"<p>Lethal toxin (LT), the major virulence factor of <i>Bacillus anthracis</i>, proteolytically inactivates MEKs and disables downstream ERK, p38 and JNK pathway signalling leading to tissue damage and mortality. Therapies for LT-induced damage after host cell internalization of the toxin are lacking. Here we constructed MEK variants in which the LT proteolytic site was modified: MEK2(P10V/A11D), MEK3(I27D) and MEK6(I15D). These variants were resistant to proteolysis by LT. Expression in cells enabled sustained activation of ERK and p38 pathways and promoted cell survival upon LT treatment. Survival of LT- or <i>B. anthracis</i>-challenged MEK variant transgenic mice also increased compared with controls. We found that LT-mediated disruption of both ERK and p38 pathway is essential for anthrax pathogenesis. We show that engagement of upstream receptor tyrosine kinases reactivated the LT-disrupted ERK pathway, as did administering a cocktail of EGF, GM-CSF and FGF2 growth factors, which significantly increased survival of LT- or <i>B. anthracis</i>-challenged mice. These findings offer potential towards developing damage-limiting therapeutic strategies for anthrax.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"15 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723243","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}

{"title":"Inducible transposon mutagenesis identifies bacterial fitness determinants during infection in mice","authors":"David W. Basta, Ian W. Campbell, Emily J. Sullivan, Julia A. Hotinger, Karthik Hullahalli, Mehek Garg, Matthew K. Waldor","doi":"10.1038/s41564-025-01975-z","DOIUrl":"https://doi.org/10.1038/s41564-025-01975-z","url":null,"abstract":"<p>Transposon insertion sequencing (Tn-seq) is a powerful method for genome-scale forward genetics in bacteria. However, inefficient transposon delivery or stochastic loss of mutants due to population bottlenecks can limit its effectiveness. Here we have developed ‘InducTn-seq’, where an arabinose-inducible Tn5 transposase enables temporal control of mini-Tn5 transposition. InducTn-seq generated up to 1.2 million transposon mutants from a single colony of enterotoxigenic <i>Escherichia coli</i>, <i>Salmonella typhimurium</i>, <i>Shigella flexneri</i> and <i>Citrobacter rodentium</i>. This mutant diversity enabled more sensitive detection of subtle fitness defects and measurement of quantitative fitness effects for essential and non-essential genes. Applying InducTn-seq to <i>C. rodentium</i> in a mouse model of infectious colitis bypassed a highly restrictive host bottleneck, generating a diverse population of &gt;5 × 10⁵ unique transposon mutants compared to 10–10² recovered by traditional Tn-seq. This in vivo screen revealed that the <i>C. rodentium</i> type I-E CRISPR system is required to suppress a toxin otherwise activated during gut colonization. Our findings highlight the potential of InducTn-seq for genome-scale forward genetic screens in bacteria.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"20 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712978","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}

{"title":"Publisher Correction: Baloxavir improves disease outcomes in mice after intranasal or ocular infection with Influenza A virus H5N1-contaminated cow’s milk","authors":"Jeremy C. Jones,&nbsp;Konstantin Andreev,&nbsp;Thomas P. Fabrizio,&nbsp;Andrew S. Bowman,&nbsp;Elena A. Govorkova,&nbsp;Richard J. Webby","doi":"10.1038/s41564-025-01994-w","DOIUrl":"10.1038/s41564-025-01994-w","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 4","pages":"1026-1026"},"PeriodicalIF":20.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-025-01994-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713319","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}

{"title":"Characterizing extracellular vesicles of human fungal pathogens","authors":"Marcio L. Rodrigues,&nbsp;Guilhem Janbon,&nbsp;Richard J. O’Connell,&nbsp;Thi-Thu-Huyen Chu,&nbsp;Robin C. May,&nbsp;Hailing Jin,&nbsp;Flavia C. G. Reis,&nbsp;Lysangela R. Alves,&nbsp;Rosana Puccia,&nbsp;Taicia P. Fill,&nbsp;Juliana Rizzo,&nbsp;Daniel Zamith-Miranda,&nbsp;Kildare Miranda,&nbsp;Teresa Gonçalves,&nbsp;Iuliana V. Ene,&nbsp;Mehdi Kabani,&nbsp;Marilyn Anderson,&nbsp;Neil A. R. Gow,&nbsp;David R. Andes,&nbsp;Arturo Casadevall,&nbsp;Joshua D. Nosanchuk,&nbsp;Leonardo Nimrichter","doi":"10.1038/s41564-025-01962-4","DOIUrl":"10.1038/s41564-025-01962-4","url":null,"abstract":"Since their discovery in 2007, there has been growing awareness of the importance of fungal extracellular vesicles (EVs) for fungal physiology, host–pathogen interactions and virulence. Fungal EVs are nanostructures comprising bilayered membranes and molecules of various types that participate in several pathophysiological processes in fungal biology, including secretion, cellular communication, immunopathogenesis and drug resistance. However, many questions remain regarding the classification of EVs, their cellular origin, passage across the cell wall, experimental models for functional and compositional analyses, production in vitro and in vivo and biomarkers for EVs. Here, we discuss gaps in the literature of fungal EVs and identify key questions for the field. We present the history of fungal EV discovery, discuss five major unanswered questions in fungal EV biology and provide future perspectives for fungal EV research. We primarily focus our discussion on human fungal pathogens, but also extend it to include knowledge of other fungi, such as plant pathogens. With this Perspective we hope to stimulate new approaches and expand studies to understand the biology of fungal EVs. In this Perspective, Rodrigues et al. discuss the discovery of fungal extracellular vesicles, key unanswered questions in the field and future research directions.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 4","pages":"825-835"},"PeriodicalIF":20.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712980","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}

{"title":"Processing-bias correction with DEBIAS-M improves cross-study generalization of microbiome-based prediction models","authors":"George I. Austin,&nbsp;Aya Brown Kav,&nbsp;Shahd ElNaggar,&nbsp;Heekuk Park,&nbsp;Jana Biermann,&nbsp;Anne-Catrin Uhlemann,&nbsp;Itsik Pe’er,&nbsp;Tal Korem","doi":"10.1038/s41564-025-01954-4","DOIUrl":"10.1038/s41564-025-01954-4","url":null,"abstract":"Every step in common microbiome profiling protocols has variable efficiency for each microbe, for example, different DNA extraction efficiency for Gram-positive bacteria. These processing biases impede the identification of signals that are biologically interpretable and generalizable across studies. ‘Batch-correction’ methods have been used to address these issues computationally with some success, but they are largely non-interpretable and often require the use of an outcome variable in a manner that risks overfitting. We present DEBIAS-M (domain adaptation with phenotype estimation and batch integration across studies of the microbiome), an interpretable framework for inference and correction of processing bias, which facilitates domain adaptation in microbiome studies. DEBIAS-M learns bias-correction factors for each microbe in each batch that simultaneously minimize batch effects and maximize cross-study associations with phenotypes. Using diverse benchmarks including 16S rRNA and metagenomic sequencing, classification and regression, and a variety of clinical and molecular targets, we demonstrate that using DEBIAS-M improves cross-study prediction accuracy compared with commonly used batch-correction methods. Notably, we show that the inferred bias-correction factors are stable, interpretable and strongly associated with specific experimental protocols. Overall, we show that DEBIAS-M facilitates improved modelling of microbiome data and identification of interpretable signals that generalize across studies. DEBIAS-M corrects technical variability in microbiome data in a manner both interpretable and suitable for machine learning. In extensive benchmarks, DEBIAS-M facilitates robust analyses that generalize across datasets.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 4","pages":"897-911"},"PeriodicalIF":20.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712979","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}

{"title":"Immune targeting and host-protective effects of the latent stage of Toxoplasma gondii","authors":"Julia N. Eberhard,&nbsp;Lindsey A. Shallberg,&nbsp;Aaron Winn,&nbsp;Sambamurthy Chandrasekaran,&nbsp;Christopher J. Giuliano,&nbsp;Emily F. Merritt,&nbsp;Elinor Willis,&nbsp;Christoph Konradt,&nbsp;David A. Christian,&nbsp;Daniel L. Aldridge,&nbsp;Molly E. Bunkofske,&nbsp;Maxime Jacquet,&nbsp;Florence Dzierszinski,&nbsp;Eleni Katifori,&nbsp;Sebastian Lourido,&nbsp;Anita A. Koshy,&nbsp;Christopher A. Hunter","doi":"10.1038/s41564-025-01967-z","DOIUrl":"10.1038/s41564-025-01967-z","url":null,"abstract":"Latency is a microbial strategy for persistence. For Toxoplasma gondii the bradyzoite stage forms long-lived cysts critical for transmission, and its presence in neurons is considered important for immune evasion. However, the extent to which cyst formation escapes immune pressure and mediates persistence remained unclear. Here we developed a mathematical model highlighting that bradyzoite-directed immunity contributes to control of cyst numbers. In vivo studies demonstrated that transgenic CD8+ T cells recognized a cyst-derived antigen, and neuronal STAT1 signalling promoted cyst control in mice. Modelling and experiments with parasites unable to form bradyzoites (Δbfd1) revealed that the absence of cyst formation in the central nervous system did not prevent long-term persistence but resulted in increased tachyzoite replication with associated tissue damage and mortality. These findings suggest the latent form of T. gondii is under immune pressure, mitigates infection-induced damage and promotes survival of host and parasite. In vivo and in silico analyses suggest that bradyzoite-directed immunity contributes to control of cyst numbers, tissue damage and mortality in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 4","pages":"992-1005"},"PeriodicalIF":20.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-025-01967-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712981","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}