Nature Microbiology最新文献

{"title":"The Parkinson’s disease drug entacapone disrupts gut microbiome homoeostasis via iron sequestration","authors":"Fátima C. Pereira, Xiaowei Ge, Jannie M. Kristensen, Rasmus H. Kirkegaard, Klara Maritsch, Dávid Szamosvári, Stefanie Imminger, David Seki, Juwairiyah B. Shazzad, Yifan Zhu, Marie Decorte, Bela Hausmann, David Berry, Kenneth Wasmund, Arno Schintlmeister, Thomas Böttcher, Ji-Xin Cheng, Michael Wagner","doi":"10.1038/s41564-024-01853-0","DOIUrl":"https://doi.org/10.1038/s41564-024-01853-0","url":null,"abstract":"<p>Many human-targeted drugs alter the gut microbiome, leading to implications for host health. However, the mechanisms underlying these effects are not well known. Here we combined quantitative microbiome profiling, long-read metagenomics, stable isotope probing and single-cell chemical imaging to investigate the impact of two widely prescribed drugs on the gut microbiome. Physiologically relevant concentrations of entacapone, a treatment for Parkinson’s disease, or loxapine succinate, used to treat schizophrenia, were incubated ex vivo with human faecal samples. Both drugs significantly impact microbial activity, more so than microbial abundance. Mechanistically, entacapone can complex and deplete available iron resulting in gut microbiome composition and function changes. Microbial growth can be rescued by replenishing levels of microbiota-accessible iron. Further, entacapone-induced iron starvation selected for iron-scavenging gut microbiome members encoding antimicrobial resistance and virulence genes. These findings reveal the impact of two under-investigated drugs on whole microbiomes and identify metal sequestration as a mechanism of drug-induced microbiome disturbance.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"3 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678277","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":"Engineering history with Asgard archaea of the kingdom Promethearchaeati","authors":"Masaru K. Nobu","doi":"10.1038/s41564-024-01866-9","DOIUrl":"https://doi.org/10.1038/s41564-024-01866-9","url":null,"abstract":"Multiple histories converge in Masaru Nobu’s story of culturing an archaeon closely related to us eukaryotes.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"251 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673236","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":"Coffee habits help shape gut communities","authors":"Nathan P. McNulty, Jeffrey I. Gordon","doi":"10.1038/s41564-024-01869-6","DOIUrl":"https://doi.org/10.1038/s41564-024-01869-6","url":null,"abstract":"Routine coffee consumption is associated with a gut microbiome signature characterized by elevated levels of Lawsonibacter asaccharolyticus. The growth of this bacterium is stimulated by coffee in vitro and its activities may influence the biotransformation of coffee-associated metabolites.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"69 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673227","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":"A foldon-free prefusion F trimer vaccine for respiratory syncytial virus to reduce off-target immune responses","authors":"Mark J. G. Bakkers, Freek Cox, Annemart Koornneef, Xiaodi Yu, Daan van Overveld, Lam Le, Ward van den Hoogen, Joost Vaneman, Anne Thoma, Richard Voorzaat, Lisanne Tettero, Jarek Juraszek, Leslie van der Fits, Roland Zahn, Johannes P. M. Langedijk","doi":"10.1038/s41564-024-01860-1","DOIUrl":"https://doi.org/10.1038/s41564-024-01860-1","url":null,"abstract":"<p>Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and older people. Current RSV subunit vaccines are based on a fusion protein that is stabilized in the prefusion conformation and linked to a heterologous foldon trimerization domain to obtain a prefusion F (preF) trimer. Here we show that current RSV vaccines induce undesirable anti-foldon antibodies in non-human primates, mice and humans. To overcome this, we designed a foldon-free RSV preF trimer by elucidating the structural basis of trimerization-induced preF destabilization through molecular dynamics simulations and by introducing amino acid substitutions that negate hotspots of charge repulsion. The highly stable prefusion conformation was validated using antigenic and cryo-electron microscopy analysis. The preF is immunogenic and protective in naive mouse models and boosts neutralizing antibody titres in RSV-pre-exposed mice and non-human primates, while achieving similar titres to approved RSV vaccines in mice. This stable preF design is a promising option as a foldon-independent candidate for a next-generation RSV vaccine immunogen.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"53 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673234","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":"Acquired amphotericin B resistance leads to fitness trade-offs that can be mitigated by compensatory evolution in Candida auris","authors":"Hans Carolus, Dimitrios Sofras, Giorgio Boccarella, Poppy Sephton-Clark, Vladislav Biriukov, Nicholas C. Cauldron, Celia Lobo Romero, Rudy Vergauwen, Saleh Yazdani, Siebe Pierson, Stef Jacobs, Paul Vandecruys, Stefanie Wijnants, Jacques F. Meis, Toni Gabaldón, Pieter van den Berg, Jeffrey M. Rybak, Christina A. Cuomo, Patrick Van Dijck","doi":"10.1038/s41564-024-01854-z","DOIUrl":"https://doi.org/10.1038/s41564-024-01854-z","url":null,"abstract":"<p><i>Candida auris</i> is a growing concern due to its resistance to antifungal drugs, particularly amphotericin B (AMB), detected in 30 to 60% of clinical isolates. However, the mechanisms of AMB resistance remain poorly understood. Here we investigated 441 in vitro- and in vivo-evolved <i>C. auris</i> lineages from 4 AMB-susceptible clinical strains of different clades. Genetic and sterol analyses revealed four major types of sterol alterations as a result of clinically rare variations in sterol biosynthesis genes <i>ERG6</i>, <i>NCP1</i>, <i>ERG11</i>, <i>ERG3</i>, <i>HMG1</i>, <i>ERG10</i> and <i>ERG12</i>. In addition, aneuploidies in chromosomes 4 and 6 emerged during resistance evolution. Fitness trade-off phenotyping and mathematical modelling identified diverse strain- and mechanism-dependent fitness trade-offs. Variation in <i>CDC25</i> rescued fitness trade-offs, thereby increasing the infection capacity. This possibly contributed to therapy-induced acquired AMB resistance in the clinic. Our findings highlight sterol-modulating mechanisms and fitness trade-off compensation as risks for AMB treatment failure in clinical settings.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"38 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673261","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":"Enteric bacterial infection stimulates remodelling of bile metabolites to promote intestinal homeostasis","authors":"Ting Zhang, Yuko Hasegawa, Matthew K. Waldor","doi":"10.1038/s41564-024-01862-z","DOIUrl":"https://doi.org/10.1038/s41564-024-01862-z","url":null,"abstract":"<p>The liver makes bile, an aqueous solution critical for fat absorption, which is secreted into the duodenum. Despite extensive studies on bile salts, other components of bile are less well characterized. Here we used global metabolomic analysis on bile from specific-pathogen-free, germ-free, <i>Citrobacter rodentium</i>-infected or <i>Listeria monocytogenes</i>-infected mice and identified a metabolome of 812 metabolites that were altered by both microbiota and enteric infection. Hepatic transcriptomics identified enteric-infection-triggered pathways that probably underlie bile remodelling. Enteric infection increased levels of four dicarboxylates in bile, including itaconate. Analysis of <i>Acod1</i>^−/− mice indicated that increased itaconate also increased tuft cell abundance, altered microbiota composition and function as detected by metagenomic analysis, and modulated host defence, leading to reduced <i>Vibrio cholerae</i> colonization. Our data suggest that enteric-infection-associated signals are relayed between the intestine and liver and induce transcriptional programmes that shape the bile metabolome, modifying the immunomodulatory and host defence functions of bile.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"70 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673231","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":"Searching for high pathogenicity avian influenza virus in Antarctica","authors":"Begoña Aguado, Lineke Begeman, Anne Günther, Matteo Iervolino, Florencia Soto, Ralph E. T. Vanstreels, Alice Reade, Adam Coerper, Ben Wallis, Antonio Alcamí, Meagan Dewar","doi":"10.1038/s41564-024-01868-7","DOIUrl":"https://doi.org/10.1038/s41564-024-01868-7","url":null,"abstract":"<p>The current panzootic spread of high pathogenicity avian influenza virus (HPAIV) subtype H5N1 clade 2.3.4.4b has caused unprecedented mortality in wild animals worldwide¹. In 2022, the virus caused mass mortality of seabirds and marine mammals in South America, which raised concerns about HPAIV spreading to Antarctica. The wildlife in Antarctica is seasonally dense due to high populations found in breading colonies of birds and mammals, and many Antarctic sites are remote and difficult to access, meaning that HPAIV could have dramatic effects on its fauna without immediately being noticed. As a result, surveillance efforts in this area are crucial.</p><p>The detection of HPAIV in the sub-Antarctic islands of South Georgia was first reported in October 2023. It caused considerable mortalities of seabirds (for example, skuas, gulls and albatrosses) and marine mammals (for example, elephant seals and sea lions) during the subsequent months². Recent phylogenetic analyses of the viral sequences from South Georgia demonstrated a single introduction from South America². Wildlife mortality suspected to be related to HPAIV was reported in Antarctica as early as November 2023 (ref. ³). The first case of HPAIV in Antarctica was confirmed in skuas (<i>Stercorarius</i> sp.) found dead in January 2024 near the Argentinian Primavera Base (Danco Coast, Antarctic Peninsula) and tested in February 2024 in a molecular diagnostic laboratory set up at the Spanish Gabriel de Castilla Station (Deception Island, South Shetland Islands)⁴. Having this on-site laboratory showed it was possible to perform the diagnoses in Antarctica itself, which gives results much faster and avoids the risk of losing sample quality during transport to laboratories outside Antarctica. HPAIV was later reported in dead skuas near the Czech Johann Gregor Mendel base⁵. The finding of sporadic or potential cases of HPAIV-infected skuas indicated that the virus had reached Antarctica. In response, we launched the Australis expedition to investigate the spread and impact of HPAIV at several remote sites, following a direct field diagnostic approach with a mobile laboratory on board.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"22 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673235","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":"Bacterial chemotaxis toward virus-infected cyanobacteria","authors":"Uri Sheyn, Maria P. Erazo-Garcia, Frank O. Aylward","doi":"10.1038/s41564-024-01867-8","DOIUrl":"https://doi.org/10.1038/s41564-024-01867-8","url":null,"abstract":"During the pre-lysis phases of phage infection, the cyanobacterium Synechococcus releases metabolites that attract heterotrophic bacteria — a process that is likely to influence carbon fate in the ocean.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"250 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670680","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":"Coffee consumption is associated with intestinal Lawsonibacter asaccharolyticus abundance and prevalence across multiple cohorts","authors":"Paolo Manghi, Amrisha Bhosle, Kai Wang, Roberta Marconi, Marta Selma-Royo, Liviana Ricci, Francesco Asnicar, Davide Golzato, Wenjie Ma, Dong Hang, Kelsey N. Thompson, Eric A. Franzosa, Amir Nabinejad, Sabrina Tamburini, Eric B. Rimm, Wendy S. Garrett, Qi Sun, Andrew T. Chan, Mireia Valles-Colomer, Manimozhiyan Arumugam, Kate M. Bermingham, Francesca Giordano, Richard Davies, George Hadjigeorgiou, Jonathan Wolf, Till Strowig, Sarah E. Berry, Curtis Huttenhower, Tim D. Spector, Nicola Segata, Mingyang Song","doi":"10.1038/s41564-024-01858-9","DOIUrl":"https://doi.org/10.1038/s41564-024-01858-9","url":null,"abstract":"<p>Although diet is a substantial determinant of the human gut microbiome, the interplay between specific foods and microbial community structure remains poorly understood. Coffee is a habitually consumed beverage with established metabolic and health benefits. We previously found that coffee is, among &gt;150 items, the food showing the highest correlation with microbiome components. Here we conducted a multi-cohort, multi-omic analysis of US and UK populations with detailed dietary information from a total of 22,867 participants, which we then integrated with public data from 211 cohorts (<i>N</i> = 54,198). The link between coffee consumption and microbiome was highly reproducible across different populations (area under the curve of 0.89), largely driven by the presence and abundance of the species <i>Lawsonibacter asaccharolyticus</i>. Using in vitro experiments, we show that coffee can stimulate growth of <i>L.</i> <i>asaccharolyticus</i>. Plasma metabolomics on 438 samples identified several metabolites enriched among coffee consumers, with quinic acid and its potential derivatives associated with coffee and <i>L.</i> <i>asaccharolyticus</i>. This study reveals a metabolic link between a specific gut microorganism and a specific food item, providing a framework for the understanding of microbial dietary responses at the biochemical level.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"50 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665488","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":"Dietary zinc deficiency promotes Acinetobacter baumannii lung infection via IL-13 in mice","authors":"Lauren D. Palmer, Kacie A. Traina, Lillian J. Juttukonda, Zachery R. Lonergan, Dziedzom A. Bansah, Xiaomei Ren, John H. Geary, Christopher Pinelli, Kelli L. Boyd, Tzushan S. Yang, Eric P. Skaar","doi":"10.1038/s41564-024-01849-w","DOIUrl":"https://doi.org/10.1038/s41564-024-01849-w","url":null,"abstract":"<p>Dietary zinc deficiency is a major risk factor for pneumonia. <i>Acinetobacter baumannii</i> is a leading cause of ventilator-associated pneumonia and a critical public health threat due to increasing rates of multidrug resistance. Patient populations at increased risk for <i>A. baumannii</i> pneumonia are also at increased risk of zinc deficiency. Here we established a mouse model of dietary zinc deficiency and acute <i>A. baumannii</i> pneumonia to test the hypothesis that host zinc deficiency contributes to <i>A. baumannii</i> pathogenesis. We showed that zinc-deficient mice have significantly increased <i>A. baumannii</i> burdens in the lungs, dissemination to the spleen and higher mortality. During infection, zinc-deficient mice produce more pro-inflammatory cytokines, including IL-13. Administration of IL-13 promotes <i>A. baumannii</i> dissemination in zinc-sufficient mice, while antibody neutralization of IL-13 protects zinc-deficient mice from <i>A. baumannii</i> dissemination and mortality during infection. These data highlight the therapeutic potential of anti-IL-13 antibody treatments, which are well tolerated in humans, for the treatment of pneumonia.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"75 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637062","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}