Pub Date : 2024-11-20DOI: 10.1038/s41564-024-01869-6
Nathan P. McNulty, Jeffrey I. Gordon
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.
{"title":"Coffee habits help shape gut communities","authors":"Nathan P. McNulty, Jeffrey I. Gordon","doi":"10.1038/s41564-024-01869-6","DOIUrl":"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":"9 12","pages":"3088-3089"},"PeriodicalIF":20.5,"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}
Pub Date : 2024-11-20DOI: 10.1038/s41564-024-01860-1
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
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. A targeted design to stabilize the respiratory syncytial virus prefusion F trimer enables the generation of a foldon-free immunogen that elicits similar humoral responses to approved vaccines.
{"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":"10.1038/s41564-024-01860-1","url":null,"abstract":"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. A targeted design to stabilize the respiratory syncytial virus prefusion F trimer enables the generation of a foldon-free immunogen that elicits similar humoral responses to approved vaccines.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 12","pages":"3254-3267"},"PeriodicalIF":20.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01860-1.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1038/s41564-024-01854-z
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
Candida auris 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 C. auris 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 ERG6, NCP1, ERG11, ERG3, HMG1, ERG10 and ERG12. 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 CDC25 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. The fungal pathogen Candida auris can acquire amphotericin B resistance through clinically rare mutations in sterol biosynthesis genes but at a certain fitness cost, which reduces its infection potential. Compensatory evolution can, however, mitigate this cost.
由于白色念珠菌对抗真菌药物，尤其是两性霉素 B（AMB）产生耐药性，30% 至 60% 的临床分离菌株对 AMB 产生耐药性，因此白色念珠菌日益受到关注。然而，人们对 AMB 的耐药性机制仍然知之甚少。在这里，我们研究了 441 个体外和体内进化的 C. auris 菌系，这些菌系来自 4 个对 AMB 敏感的不同支系的临床菌株。遗传和固醇分析显示，由于临床上罕见的固醇生物合成基因 ERG6、NCP1、ERG11、ERG3、HMG1、ERG10 和 ERG12 的变异，导致四种主要类型的固醇改变。此外，在抗药性进化过程中还出现了 4 号和 6 号染色体的非整倍体。适应性权衡表型分析和数学建模确定了多种依赖于菌株和机制的适应性权衡。CDC25 的变异可消除适应性权衡，从而提高感染能力。这可能是临床治疗中获得性 AMB 耐药性的原因之一。我们的研究结果突出表明，固醇调节机制和适应性权衡补偿是临床环境中 AMB 治疗失败的风险所在。
{"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":"10.1038/s41564-024-01854-z","url":null,"abstract":"Candida auris 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 C. auris 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 ERG6, NCP1, ERG11, ERG3, HMG1, ERG10 and ERG12. 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 CDC25 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. The fungal pathogen Candida auris can acquire amphotericin B resistance through clinically rare mutations in sterol biosynthesis genes but at a certain fitness cost, which reduces its infection potential. Compensatory evolution can, however, mitigate this cost.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 12","pages":"3304-3320"},"PeriodicalIF":20.5,"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}
Pub Date : 2024-11-20DOI: 10.1038/s41564-024-01862-z
Ting Zhang, Yuko Hasegawa, Matthew K. Waldor
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, Citrobacter rodentium-infected or Listeria monocytogenes-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 Acod1−/− 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 Vibrio cholerae 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. Metabolomic analysis of bile after infection by enteric bacteria in mice reveals composition changes including increased itaconate levels that promote intestinal homeostasis and reduce Vibrio cholerae colonization.
{"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":"10.1038/s41564-024-01862-z","url":null,"abstract":"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, Citrobacter rodentium-infected or Listeria monocytogenes-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 Acod1−/− 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 Vibrio cholerae 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. Metabolomic analysis of bile after infection by enteric bacteria in mice reveals composition changes including increased itaconate levels that promote intestinal homeostasis and reduce Vibrio cholerae colonization.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 12","pages":"3376-3390"},"PeriodicalIF":20.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01862-z.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1038/s41564-024-01868-7
Begoña Aguado, Lineke Begeman, Anne Günther, Matteo Iervolino, Florencia Soto, Ralph E. T. Vanstreels, Alice Reade, Adam Coerper, Ben Wallis, Antonio Alcamí, Meagan Dewar
{"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":"10.1038/s41564-024-01868-7","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 12","pages":"3081-3083"},"PeriodicalIF":20.5,"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}
Pub Date : 2024-11-19DOI: 10.1038/s41564-024-01867-8
Uri Sheyn, Maria P. Erazo-Garcia, Frank O. Aylward
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.
{"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":"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":"9 12","pages":"3093-3094"},"PeriodicalIF":20.5,"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}
Pub Date : 2024-11-18DOI: 10.1038/s41564-024-01858-9
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
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 >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 (N = 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 Lawsonibacter asaccharolyticus. Using in vitro experiments, we show that coffee can stimulate growth of L. asaccharolyticus. Plasma metabolomics on 438 samples identified several metabolites enriched among coffee consumers, with quinic acid and its potential derivatives associated with coffee and L. asaccharolyticus. 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. Coffee consumption is associated with the presence and abundance of a specific member of the human gut microbiome, Lawsonibacter asaccharolyticus, and changes to the plasma metabolome.
{"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":"10.1038/s41564-024-01858-9","url":null,"abstract":"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 >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 (N = 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 Lawsonibacter asaccharolyticus. Using in vitro experiments, we show that coffee can stimulate growth of L. asaccharolyticus. Plasma metabolomics on 438 samples identified several metabolites enriched among coffee consumers, with quinic acid and its potential derivatives associated with coffee and L. asaccharolyticus. 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. Coffee consumption is associated with the presence and abundance of a specific member of the human gut microbiome, Lawsonibacter asaccharolyticus, and changes to the plasma metabolome.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 12","pages":"3120-3134"},"PeriodicalIF":20.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01858-9.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1038/s41564-024-01849-w
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
Dietary zinc deficiency is a major risk factor for pneumonia. Acinetobacter baumannii 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 A. baumannii pneumonia are also at increased risk of zinc deficiency. Here we established a mouse model of dietary zinc deficiency and acute A. baumannii pneumonia to test the hypothesis that host zinc deficiency contributes to A. baumannii pathogenesis. We showed that zinc-deficient mice have significantly increased A. baumannii 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 A. baumannii dissemination in zinc-sufficient mice, while antibody neutralization of IL-13 protects zinc-deficient mice from A. baumannii 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. Increased IL-13 drives increased bacterial dissemination and mortality following Acinetobacter baumannii lung infection of zinc-deficient mice and can be countered by anti-IL-13 antibody therapy.
{"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":"10.1038/s41564-024-01849-w","url":null,"abstract":"Dietary zinc deficiency is a major risk factor for pneumonia. Acinetobacter baumannii 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 A. baumannii pneumonia are also at increased risk of zinc deficiency. Here we established a mouse model of dietary zinc deficiency and acute A. baumannii pneumonia to test the hypothesis that host zinc deficiency contributes to A. baumannii pathogenesis. We showed that zinc-deficient mice have significantly increased A. baumannii 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 A. baumannii dissemination in zinc-sufficient mice, while antibody neutralization of IL-13 protects zinc-deficient mice from A. baumannii 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. Increased IL-13 drives increased bacterial dissemination and mortality following Acinetobacter baumannii lung infection of zinc-deficient mice and can be countered by anti-IL-13 antibody therapy.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 12","pages":"3196-3209"},"PeriodicalIF":20.5,"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}
Pub Date : 2024-11-15DOI: 10.1038/s41564-024-01843-2
Richard J. Henshaw, Jonathan Moon, Michael R. Stehnach, Benjamin P. Bowen, Suzanne M. Kosina, Trent R. Northen, Jeffrey S. Guasto, Sheri A. Floge
Chemical cues mediate interactions between marine phytoplankton and bacteria, underpinning ecosystem-scale processes including nutrient cycling and carbon fixation. Phage infection alters host metabolism, stimulating the release of chemical cues from intact plankton, but how these dynamics impact ecology and biogeochemistry is poorly understood. Here we determine the impact of phage infection on dissolved metabolite pools from marine cyanobacteria and the subsequent chemotactic response of heterotrophic bacteria using time-resolved metabolomics and microfluidics. Metabolites released from intact, phage-infected Synechococcus elicited strong chemoattraction from Vibrio alginolyticus and Pseudoalteromonas haloplanktis, especially during early infection stages. Sustained bacterial chemotaxis occurred towards live-infected Synechococcus, contrasted by no discernible chemotaxis towards uninfected cyanobacteria. High-throughput microfluidics identified 5′-deoxyadenosine and 5′-methylthioadenosine as key attractants. Our findings establish that, before lysis, phage-infected picophytoplankton release compounds that attract motile heterotrophic bacteria, suggesting a mechanism for resource transfer that might impact carbon and nutrient fluxes across trophic levels. The authors use time-resolved metabolomics and microfluidics to characterize enhanced heterotroph chemoattraction to metabolites released from cyanobacteria during early stages of phage infection.
{"title":"Metabolites from intact phage-infected Synechococcus chemotactically attract heterotrophic marine bacteria","authors":"Richard J. Henshaw, Jonathan Moon, Michael R. Stehnach, Benjamin P. Bowen, Suzanne M. Kosina, Trent R. Northen, Jeffrey S. Guasto, Sheri A. Floge","doi":"10.1038/s41564-024-01843-2","DOIUrl":"10.1038/s41564-024-01843-2","url":null,"abstract":"Chemical cues mediate interactions between marine phytoplankton and bacteria, underpinning ecosystem-scale processes including nutrient cycling and carbon fixation. Phage infection alters host metabolism, stimulating the release of chemical cues from intact plankton, but how these dynamics impact ecology and biogeochemistry is poorly understood. Here we determine the impact of phage infection on dissolved metabolite pools from marine cyanobacteria and the subsequent chemotactic response of heterotrophic bacteria using time-resolved metabolomics and microfluidics. Metabolites released from intact, phage-infected Synechococcus elicited strong chemoattraction from Vibrio alginolyticus and Pseudoalteromonas haloplanktis, especially during early infection stages. Sustained bacterial chemotaxis occurred towards live-infected Synechococcus, contrasted by no discernible chemotaxis towards uninfected cyanobacteria. High-throughput microfluidics identified 5′-deoxyadenosine and 5′-methylthioadenosine as key attractants. Our findings establish that, before lysis, phage-infected picophytoplankton release compounds that attract motile heterotrophic bacteria, suggesting a mechanism for resource transfer that might impact carbon and nutrient fluxes across trophic levels. The authors use time-resolved metabolomics and microfluidics to characterize enhanced heterotroph chemoattraction to metabolites released from cyanobacteria during early stages of phage infection.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 12","pages":"3184-3195"},"PeriodicalIF":20.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637054","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}
Difficulties in antibiotic treatment of Mycobacterium tuberculosis (Mtb) are partly thought to be due to heterogeneity in growth. Although the ability of bacterial pathogens to regulate growth is crucial to control homeostasis, virulence and drug responses, single-cell growth and cell cycle behaviours of Mtb are poorly characterized. Here we use time-lapse, single-cell imaging of Mtb coupled with mathematical modelling to observe asymmetric growth and heterogeneity in cell size, interdivision time and elongation speed. We find that, contrary to Mycobacterium smegmatis, Mtb initiates cell growth not only from the old pole but also from new poles or both poles. Whereas most organisms grow exponentially at the single-cell level, Mtb has a linear growth mode. Our data show that the growth behaviour of Mtb diverges from that of model bacteria, provide details into how Mtb grows and creates heterogeneity and suggest that growth regulation may also diverge from that in other bacteria. Time-lapse imaging of Mycobacterium tuberculosis cells loaded in microfluidic chambers reveals heterogeneity in growth characteristics, atypical modes of polar growth initiation and linear growth at the single-cell level.
{"title":"Single-cell imaging of the Mycobacterium tuberculosis cell cycle reveals linear and heterogenous growth","authors":"Eun Seon Chung, Prathitha Kar, Maliwan Kamkaew, Ariel Amir, Bree B. Aldridge","doi":"10.1038/s41564-024-01846-z","DOIUrl":"10.1038/s41564-024-01846-z","url":null,"abstract":"Difficulties in antibiotic treatment of Mycobacterium tuberculosis (Mtb) are partly thought to be due to heterogeneity in growth. Although the ability of bacterial pathogens to regulate growth is crucial to control homeostasis, virulence and drug responses, single-cell growth and cell cycle behaviours of Mtb are poorly characterized. Here we use time-lapse, single-cell imaging of Mtb coupled with mathematical modelling to observe asymmetric growth and heterogeneity in cell size, interdivision time and elongation speed. We find that, contrary to Mycobacterium smegmatis, Mtb initiates cell growth not only from the old pole but also from new poles or both poles. Whereas most organisms grow exponentially at the single-cell level, Mtb has a linear growth mode. Our data show that the growth behaviour of Mtb diverges from that of model bacteria, provide details into how Mtb grows and creates heterogeneity and suggest that growth regulation may also diverge from that in other bacteria. Time-lapse imaging of Mycobacterium tuberculosis cells loaded in microfluidic chambers reveals heterogeneity in growth characteristics, atypical modes of polar growth initiation and linear growth at the single-cell level.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 12","pages":"3332-3344"},"PeriodicalIF":20.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01846-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637049","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}
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