Pub Date : 2024-09-06DOI: 10.1038/s41564-024-01804-9
Yan Shao, Cristina Garcia-Mauriño, Simon Clare, Nicholas J. R. Dawson, Andre Mu, Anne Adoum, Katherine Harcourt, Junyan Liu, Hilary P. Browne, Mark D. Stares, Alison Rodger, Peter Brocklehurst, Nigel Field, Trevor D. Lawley
Human microbiota assembly commences at birth, seeded by both maternal and environmental microorganisms. Ecological theory postulates that primary colonizers dictate microbial community assembly outcomes, yet such microbial priority effects in the human gut remain underexplored. Here using longitudinal faecal metagenomics, we characterized neonatal microbiota assembly for a cohort of 1,288 neonates from the UK. We show that the pioneering neonatal gut microbiota can be stratified into one of three distinct community states, each dominated by a single microbial species and influenced by clinical and host factors, such as maternal age, ethnicity and parity. A community state dominated by Enterococcus faecalis displayed stochastic microbiota assembly with persistent high pathogen loads into infancy. In contrast, community states dominated by Bifidobacterium, specifically B. longum and particularly B. breve, exhibited a stable assembly trajectory and long-term pathogen colonization resistance, probably due to strain-specific functional adaptions to a breast milk-rich neonatal diet. Consistent with our human cohort observation, B. breve demonstrated priority effects and conferred pathogen colonization resistance in a germ-free mouse model. Our findings solidify the crucial role of Bifidobacteria as primary colonizers in shaping the microbiota assembly and functions in early life. Primary colonization by microbial communities dominated by Bifidobacteria contribute to stable gut microbiota assembly and long-term pathogen resistance in neonates.
{"title":"Primary succession of Bifidobacteria drives pathogen resistance in neonatal microbiota assembly","authors":"Yan Shao, Cristina Garcia-Mauriño, Simon Clare, Nicholas J. R. Dawson, Andre Mu, Anne Adoum, Katherine Harcourt, Junyan Liu, Hilary P. Browne, Mark D. Stares, Alison Rodger, Peter Brocklehurst, Nigel Field, Trevor D. Lawley","doi":"10.1038/s41564-024-01804-9","DOIUrl":"10.1038/s41564-024-01804-9","url":null,"abstract":"Human microbiota assembly commences at birth, seeded by both maternal and environmental microorganisms. Ecological theory postulates that primary colonizers dictate microbial community assembly outcomes, yet such microbial priority effects in the human gut remain underexplored. Here using longitudinal faecal metagenomics, we characterized neonatal microbiota assembly for a cohort of 1,288 neonates from the UK. We show that the pioneering neonatal gut microbiota can be stratified into one of three distinct community states, each dominated by a single microbial species and influenced by clinical and host factors, such as maternal age, ethnicity and parity. A community state dominated by Enterococcus faecalis displayed stochastic microbiota assembly with persistent high pathogen loads into infancy. In contrast, community states dominated by Bifidobacterium, specifically B. longum and particularly B. breve, exhibited a stable assembly trajectory and long-term pathogen colonization resistance, probably due to strain-specific functional adaptions to a breast milk-rich neonatal diet. Consistent with our human cohort observation, B. breve demonstrated priority effects and conferred pathogen colonization resistance in a germ-free mouse model. Our findings solidify the crucial role of Bifidobacteria as primary colonizers in shaping the microbiota assembly and functions in early life. Primary colonization by microbial communities dominated by Bifidobacteria contribute to stable gut microbiota assembly and long-term pathogen resistance in neonates.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 10","pages":"2570-2582"},"PeriodicalIF":20.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01804-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142418","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 : 2024-09-06DOI: 10.1038/s41564-024-01808-5
Miguel Ángel González Porras, Adrien Assié, Målin Tietjen, Marlene Violette, Manuel Kleiner, Harald Gruber-Vodicka, Nicole Dubilier, Nikolaus Leisch
A limited number of bacteria are able to colonize the nuclei of eukaryotes. ‘Candidatus Endonucleobacter’ infects the nuclei of deep-sea mussels, where it replicates to ≥80,000 bacteria per nucleus and causes nuclei to swell to 50 times their original size. How these parasites are able to replicate and avoid apoptosis is not known. Dual RNA-sequencing transcriptomes of infected nuclei isolated using laser-capture microdissection revealed that ‘Candidatus Endonucleobacter’ does not obtain most of its nutrition from nuclear DNA or RNA. Instead, ‘Candidatus Endonucleobacter’ upregulates genes for importing and digesting sugars, lipids, amino acids and possibly mucin from its host. It likely prevents apoptosis of host cells by upregulating 7–13 inhibitors of apoptosis, proteins not previously seen in bacteria. Comparative phylogenetic analyses revealed that ‘Ca. Endonucleobacter’ acquired inhibitors of apoptosis through horizontal gene transfer from their hosts. Horizontal gene transfer from eukaryotes to bacteria is assumed to be rare, but may be more common than currently recognized. ‘Candidatus Endonucleobacter’ is a pathogen of deep-sea mussels that can successfully reproduce in the nuclei of its host by expressing inhibitors of apoptosis, likely acquired through horizontal gene transfer.
{"title":"An intranuclear bacterial parasite of deep-sea mussels expresses apoptosis inhibitors acquired from its host","authors":"Miguel Ángel González Porras, Adrien Assié, Målin Tietjen, Marlene Violette, Manuel Kleiner, Harald Gruber-Vodicka, Nicole Dubilier, Nikolaus Leisch","doi":"10.1038/s41564-024-01808-5","DOIUrl":"10.1038/s41564-024-01808-5","url":null,"abstract":"A limited number of bacteria are able to colonize the nuclei of eukaryotes. ‘Candidatus Endonucleobacter’ infects the nuclei of deep-sea mussels, where it replicates to ≥80,000 bacteria per nucleus and causes nuclei to swell to 50 times their original size. How these parasites are able to replicate and avoid apoptosis is not known. Dual RNA-sequencing transcriptomes of infected nuclei isolated using laser-capture microdissection revealed that ‘Candidatus Endonucleobacter’ does not obtain most of its nutrition from nuclear DNA or RNA. Instead, ‘Candidatus Endonucleobacter’ upregulates genes for importing and digesting sugars, lipids, amino acids and possibly mucin from its host. It likely prevents apoptosis of host cells by upregulating 7–13 inhibitors of apoptosis, proteins not previously seen in bacteria. Comparative phylogenetic analyses revealed that ‘Ca. Endonucleobacter’ acquired inhibitors of apoptosis through horizontal gene transfer from their hosts. Horizontal gene transfer from eukaryotes to bacteria is assumed to be rare, but may be more common than currently recognized. ‘Candidatus Endonucleobacter’ is a pathogen of deep-sea mussels that can successfully reproduce in the nuclei of its host by expressing inhibitors of apoptosis, likely acquired through horizontal gene transfer.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2877-2891"},"PeriodicalIF":20.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01808-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142439","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 : 2024-09-06DOI: 10.1038/s41564-024-01773-z
Talia L. Karasov, Manuela Neumann, Laura Leventhal, Efthymia Symeonidi, Gautam Shirsekar, Aubrey Hawks, Grey Monroe, Pathodopsis Team, Moisés Exposito-Alonso, Joy Bergelson, Detlef Weigel, Rebecca Schwab
Plants are colonized by distinct pathogenic and commensal microbiomes across different regions of the globe, but the factors driving their geographic variation are largely unknown. Here, using 16S ribosomal DNA and shotgun sequencing, we characterized the associations of the Arabidopsis thaliana leaf microbiome with host genetics and climate variables from 267 populations in the species’ native range across Europe. Comparing the distribution of the 575 major bacterial amplicon variants (phylotypes), we discovered that microbiome composition in A. thaliana segregates along a latitudinal gradient. The latitudinal clines in microbiome composition are predicted by metrics of drought, but also by the spatial genetics of the host. To validate the relative effects of drought and host genotype we conducted a common garden field study, finding 10% of the core bacteria to be affected directly by drought and 20% to be affected by host genetic associations with drought. These data provide a valuable resource for the plant microbiome field, with the identified associations suggesting that drought can directly and indirectly shape genetic variation in A. thaliana via the leaf microbiome. The leaf microbiome compositions of 267 Arabidopsis thaliana populations across Europe reveal associations with climate and plant genetics.
在全球不同地区,植物被不同的病原微生物群和共生微生物群定植,但驱动其地理变异的因素在很大程度上是未知的。在这里,我们利用 16S 核糖体 DNA 和枪式测序技术,对拟南芥叶片微生物组与宿主遗传学和气候变量之间的关系进行了表征,这些微生物组来自拟南芥原产地欧洲的 267 个种群。通过比较 575 个主要细菌扩增子变体(系统型)的分布,我们发现拟南芥叶片微生物组的组成是沿着纬度梯度分离的。微生物组组成的纬度梯度是由干旱指标以及宿主的空间遗传学预测的。为了验证干旱和宿主基因型的相对影响,我们进行了一项普通花园田间研究,发现10%的核心细菌直接受干旱影响,20%的核心细菌受宿主基因与干旱相关性的影响。这些数据为植物微生物组领域提供了宝贵的资源,已确定的关联表明,干旱可以通过叶片微生物组直接或间接地影响连翘的遗传变异。
{"title":"Continental-scale associations of Arabidopsis thaliana phyllosphere members with host genotype and drought","authors":"Talia L. Karasov, Manuela Neumann, Laura Leventhal, Efthymia Symeonidi, Gautam Shirsekar, Aubrey Hawks, Grey Monroe, Pathodopsis Team, Moisés Exposito-Alonso, Joy Bergelson, Detlef Weigel, Rebecca Schwab","doi":"10.1038/s41564-024-01773-z","DOIUrl":"10.1038/s41564-024-01773-z","url":null,"abstract":"Plants are colonized by distinct pathogenic and commensal microbiomes across different regions of the globe, but the factors driving their geographic variation are largely unknown. Here, using 16S ribosomal DNA and shotgun sequencing, we characterized the associations of the Arabidopsis thaliana leaf microbiome with host genetics and climate variables from 267 populations in the species’ native range across Europe. Comparing the distribution of the 575 major bacterial amplicon variants (phylotypes), we discovered that microbiome composition in A. thaliana segregates along a latitudinal gradient. The latitudinal clines in microbiome composition are predicted by metrics of drought, but also by the spatial genetics of the host. To validate the relative effects of drought and host genotype we conducted a common garden field study, finding 10% of the core bacteria to be affected directly by drought and 20% to be affected by host genetic associations with drought. These data provide a valuable resource for the plant microbiome field, with the identified associations suggesting that drought can directly and indirectly shape genetic variation in A. thaliana via the leaf microbiome. The leaf microbiome compositions of 267 Arabidopsis thaliana populations across Europe reveal associations with climate and plant genetics.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 10","pages":"2748-2758"},"PeriodicalIF":20.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01773-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142419","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 : 2024-09-06DOI: 10.1038/s41564-024-01797-5
Ekansh Mittal, G. V. R. Krishna Prasad, Sandeep Upadhyay, Jully Sadadiwala, Andrew J. Olive, Guozhe Yang, Christopher M. Sassetti, Jennifer A. Philips
Mycobacterium tuberculosis (Mtb) infects several lung macrophage populations, which have distinct abilities to restrict Mtb. What enables Mtb survival in certain macrophage populations is not well understood. Here we used transposon sequencing analysis of Mtb in wild-type and autophagy-deficient mouse macrophages lacking ATG5 or ATG7, and found that Mtb genes involved in phthiocerol dimycocerosate (PDIM) virulence lipid synthesis confer resistance to autophagy. Using ppsD mutant Mtb, we found that PDIM inhibits LC3-associated phagocytosis (LAP) by inhibiting phagosome recruitment of NADPH oxidase. In mice, PDIM protected Mtb from LAP and classical autophagy. During acute infection, PDIM was dispensable for Mtb survival in alveolar macrophages but required for survival in non-alveolar macrophages in an autophagy-dependent manner. During chronic infection, autophagy-deficient mice succumbed to infection with PDIM-deficient Mtb, with impairments in B-cell accumulation in lymphoid follicles. These findings demonstrate that PDIM contributes to Mtb virulence and immune evasion, revealing a contributory role for autophagy in B-cell responses. Mycobacterial phthiocerol dimycocerosate (PDIM) inhibits LC3-associated phagocytosis and counters autophagy-dependent restriction of Mycobacterium tuberculosis in non-alveolar macrophages.
{"title":"Mycobacterium tuberculosis virulence lipid PDIM inhibits autophagy in mice","authors":"Ekansh Mittal, G. V. R. Krishna Prasad, Sandeep Upadhyay, Jully Sadadiwala, Andrew J. Olive, Guozhe Yang, Christopher M. Sassetti, Jennifer A. Philips","doi":"10.1038/s41564-024-01797-5","DOIUrl":"10.1038/s41564-024-01797-5","url":null,"abstract":"Mycobacterium tuberculosis (Mtb) infects several lung macrophage populations, which have distinct abilities to restrict Mtb. What enables Mtb survival in certain macrophage populations is not well understood. Here we used transposon sequencing analysis of Mtb in wild-type and autophagy-deficient mouse macrophages lacking ATG5 or ATG7, and found that Mtb genes involved in phthiocerol dimycocerosate (PDIM) virulence lipid synthesis confer resistance to autophagy. Using ppsD mutant Mtb, we found that PDIM inhibits LC3-associated phagocytosis (LAP) by inhibiting phagosome recruitment of NADPH oxidase. In mice, PDIM protected Mtb from LAP and classical autophagy. During acute infection, PDIM was dispensable for Mtb survival in alveolar macrophages but required for survival in non-alveolar macrophages in an autophagy-dependent manner. During chronic infection, autophagy-deficient mice succumbed to infection with PDIM-deficient Mtb, with impairments in B-cell accumulation in lymphoid follicles. These findings demonstrate that PDIM contributes to Mtb virulence and immune evasion, revealing a contributory role for autophagy in B-cell responses. Mycobacterial phthiocerol dimycocerosate (PDIM) inhibits LC3-associated phagocytosis and counters autophagy-dependent restriction of Mycobacterium tuberculosis in non-alveolar macrophages.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2970-2984"},"PeriodicalIF":20.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142732","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 : 2024-09-04DOI: 10.1038/s41564-024-01792-w
Benjamin J. Chadwick, Laura C. Ristow, Xiaofeng Xie, Damian J. Krysan, Xiaorong Lin
Cryptococcus neoformans is a ubiquitous soil fungus and airborne pathogen that causes over 180,000 deaths each year. Cryptococcus must adapt to host CO2 levels to cause disease, but the genetic basis for this adaptation is unknown. We utilized quantitative trait loci mapping with 374 progeny from a cross between a CO2-tolerant clinical isolate and a CO2-sensitive environmental isolate to identify genetic regions regulating CO2 tolerance. To identify specific quantitative trait genes, we applied fine mapping through bulk segregant analysis of near-isogenic progeny with distinct tolerance levels to CO2. We found that virulence among near-isogenic strains in a murine model of cryptococcosis correlated with CO2 tolerance. Moreover, we discovered that sensitive strains may adapt in vivo to become more CO2 tolerant and more virulent. These findings highlight the underappreciated role of CO2 tolerance and its importance in the ability of an opportunistic environmental pathogen to cause disease. Quantitative trait loci mapping reveals that tolerance to host CO2 is critical for virulence of the human fungal pathogen Cryptococcus neoformans.
{"title":"Discovery of CO2 tolerance genes associated with virulence in the fungal pathogen Cryptococcus neoformans","authors":"Benjamin J. Chadwick, Laura C. Ristow, Xiaofeng Xie, Damian J. Krysan, Xiaorong Lin","doi":"10.1038/s41564-024-01792-w","DOIUrl":"10.1038/s41564-024-01792-w","url":null,"abstract":"Cryptococcus neoformans is a ubiquitous soil fungus and airborne pathogen that causes over 180,000 deaths each year. Cryptococcus must adapt to host CO2 levels to cause disease, but the genetic basis for this adaptation is unknown. We utilized quantitative trait loci mapping with 374 progeny from a cross between a CO2-tolerant clinical isolate and a CO2-sensitive environmental isolate to identify genetic regions regulating CO2 tolerance. To identify specific quantitative trait genes, we applied fine mapping through bulk segregant analysis of near-isogenic progeny with distinct tolerance levels to CO2. We found that virulence among near-isogenic strains in a murine model of cryptococcosis correlated with CO2 tolerance. Moreover, we discovered that sensitive strains may adapt in vivo to become more CO2 tolerant and more virulent. These findings highlight the underappreciated role of CO2 tolerance and its importance in the ability of an opportunistic environmental pathogen to cause disease. Quantitative trait loci mapping reveals that tolerance to host CO2 is critical for virulence of the human fungal pathogen Cryptococcus neoformans.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 10","pages":"2684-2695"},"PeriodicalIF":20.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130750","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 : 2024-09-04DOI: 10.1038/s41564-024-01796-6
Shannon Quek, Amber Hadermann, Yang Wu, Lander De Coninck, Shrilakshmi Hegde, Jordan R. Boucher, Jessica Cresswell, Ella Foreman, Andrew Steven, E. James LaCourse, Stephen A. Ward, Samuel Wanji, Grant L. Hughes, Edward I. Patterson, Simon C. Wagstaff, Joseph D. Turner, Rhys H. Parry, Alain Kohl, Eva Heinz, Kenneth Bentum Otabil, Jelle Matthijnssens, Robert Colebunders, Mark J. Taylor
Parasitic nematodes have an intimate, chronic and lifelong exposure to vertebrate tissues. Here we mined 41 published parasitic nematode transcriptomes from vertebrate hosts and identified 91 RNA viruses across 13 virus orders from 24 families in ~70% (28 out of 41) of parasitic nematode species, which include only 5 previously reported viruses. We observe widespread distribution of virus–nematode associations across multiple continents, suggesting an ancestral acquisition event and host–virus co-evolution. Characterization of viruses of Brugia malayi (BMRV1) and Onchocerca volvulus (OVRV1) shows that these viruses are abundant in reproductive tissues of adult parasites. Importantly, the presence of BMRV1 RNA in B. malayi parasites mounts an RNA interference response against BMRV1 suggesting active viral replication. Finally, BMRV1 and OVRV1 were found to elicit antibody responses in serum samples from infected jirds and infected or exposed humans, indicating direct exposure to the immune system. Transcriptome mining, phylogenetic analysis, bioimaging and serology experiments reveal a widespread diverse virome present in ~70% of parasitic nematodes, such as Brugia malayi and Onchocerca volvulus, where some viruses are abundant in the reproductive tract and are associated with seropositivity in vertebrate hosts.
{"title":"Diverse RNA viruses of parasitic nematodes can elicit antibody responses in vertebrate hosts","authors":"Shannon Quek, Amber Hadermann, Yang Wu, Lander De Coninck, Shrilakshmi Hegde, Jordan R. Boucher, Jessica Cresswell, Ella Foreman, Andrew Steven, E. James LaCourse, Stephen A. Ward, Samuel Wanji, Grant L. Hughes, Edward I. Patterson, Simon C. Wagstaff, Joseph D. Turner, Rhys H. Parry, Alain Kohl, Eva Heinz, Kenneth Bentum Otabil, Jelle Matthijnssens, Robert Colebunders, Mark J. Taylor","doi":"10.1038/s41564-024-01796-6","DOIUrl":"10.1038/s41564-024-01796-6","url":null,"abstract":"Parasitic nematodes have an intimate, chronic and lifelong exposure to vertebrate tissues. Here we mined 41 published parasitic nematode transcriptomes from vertebrate hosts and identified 91 RNA viruses across 13 virus orders from 24 families in ~70% (28 out of 41) of parasitic nematode species, which include only 5 previously reported viruses. We observe widespread distribution of virus–nematode associations across multiple continents, suggesting an ancestral acquisition event and host–virus co-evolution. Characterization of viruses of Brugia malayi (BMRV1) and Onchocerca volvulus (OVRV1) shows that these viruses are abundant in reproductive tissues of adult parasites. Importantly, the presence of BMRV1 RNA in B. malayi parasites mounts an RNA interference response against BMRV1 suggesting active viral replication. Finally, BMRV1 and OVRV1 were found to elicit antibody responses in serum samples from infected jirds and infected or exposed humans, indicating direct exposure to the immune system. Transcriptome mining, phylogenetic analysis, bioimaging and serology experiments reveal a widespread diverse virome present in ~70% of parasitic nematodes, such as Brugia malayi and Onchocerca volvulus, where some viruses are abundant in the reproductive tract and are associated with seropositivity in vertebrate hosts.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 10","pages":"2488-2505"},"PeriodicalIF":20.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01796-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130795","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 : 2024-09-03DOI: 10.1038/s41564-024-01813-8
To successfully tackle the current mpox public-health emergency, we must learn from past outbreaks to focus research questions and take collaborative action.
{"title":"We must learn from past outbreaks","authors":"","doi":"10.1038/s41564-024-01813-8","DOIUrl":"10.1038/s41564-024-01813-8","url":null,"abstract":"To successfully tackle the current mpox public-health emergency, we must learn from past outbreaks to focus research questions and take collaborative action.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2201-2201"},"PeriodicalIF":20.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01813-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126223","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 : 2024-09-03DOI: 10.1038/s41564-024-01795-7
Xin Zhou, Audrey Hilk, Norma V. Solis, Nancy Scott, Annette Beach, Natthapon Soisangwan, Clara L. Billings, Laura S. Burrack, Scott G. Filler, Anna Selmecki
Genomic copy number changes are associated with antifungal drug resistance and virulence across diverse fungal pathogens, but the rate and dynamics of these genomic changes in the presence of antifungal drugs are unknown. Here we optimized a dual-fluorescent reporter system in the diploid pathogen Candida albicans to quantify haplotype-specific copy number variation (CNV) and loss of heterozygosity (LOH) at the single-cell level with flow cytometry. We followed the frequency and dynamics of CNV and LOH at two distinct genomic locations in the presence and absence of antifungal drugs in vitro and in a murine model of candidiasis. Copy number changes were rapid and dynamic during adaptation to fluconazole and frequently involved competing subpopulations with distinct genotypes. This study provides quantitative evidence for the rapid speed at which diverse genotypes arise and undergo dynamic population-level fluctuations during adaptation to antifungal drugs in vitro and in vivo. Development of a dual-fluorescent reporter system allows rapid quantification of diverse genomic copy number changes that arise in Candida albicans during adaptation to antifungal drugs.
{"title":"Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in Candida albicans","authors":"Xin Zhou, Audrey Hilk, Norma V. Solis, Nancy Scott, Annette Beach, Natthapon Soisangwan, Clara L. Billings, Laura S. Burrack, Scott G. Filler, Anna Selmecki","doi":"10.1038/s41564-024-01795-7","DOIUrl":"10.1038/s41564-024-01795-7","url":null,"abstract":"Genomic copy number changes are associated with antifungal drug resistance and virulence across diverse fungal pathogens, but the rate and dynamics of these genomic changes in the presence of antifungal drugs are unknown. Here we optimized a dual-fluorescent reporter system in the diploid pathogen Candida albicans to quantify haplotype-specific copy number variation (CNV) and loss of heterozygosity (LOH) at the single-cell level with flow cytometry. We followed the frequency and dynamics of CNV and LOH at two distinct genomic locations in the presence and absence of antifungal drugs in vitro and in a murine model of candidiasis. Copy number changes were rapid and dynamic during adaptation to fluconazole and frequently involved competing subpopulations with distinct genotypes. This study provides quantitative evidence for the rapid speed at which diverse genotypes arise and undergo dynamic population-level fluctuations during adaptation to antifungal drugs in vitro and in vivo. Development of a dual-fluorescent reporter system allows rapid quantification of diverse genomic copy number changes that arise in Candida albicans during adaptation to antifungal drugs.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2923-2938"},"PeriodicalIF":20.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123706","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 : 2024-09-02DOI: 10.1038/s41564-024-01729-3
James H. R. Wheeler, Kevin R. Foster, William M. Durham
Swimming bacteria navigate chemical gradients using temporal sensing to detect changes in concentration over time. Here we show that surface-attached bacteria use a fundamentally different mode of sensing during chemotaxis. We combined microfluidic experiments, massively parallel cell tracking and fluorescent reporters to study how Pseudomonas aeruginosa senses chemical gradients during pili-based ‘twitching’ chemotaxis on surfaces. Unlike swimming cells, we found that temporal changes in concentration did not induce motility changes in twitching cells. We then quantified the chemotactic behaviour of stationary cells by following changes in the sub-cellular localization of fluorescent proteins as cells are exposed to a gradient that alternates direction. These experiments revealed that P. aeruginosa cells can directly sense differences in concentration across the lengths of their bodies, even in the presence of strong temporal fluctuations. Our work thus overturns the widely held notion that bacterial cells are too small to directly sense chemical gradients in space. Microfluidic experiments reveal that surface-attached Pseudomonas aeruginosa cells directly sense differences in chemical concentration across the length of their cell bodies to guide pili-based chemotaxis.
{"title":"Individual bacterial cells can use spatial sensing of chemical gradients to direct chemotaxis on surfaces","authors":"James H. R. Wheeler, Kevin R. Foster, William M. Durham","doi":"10.1038/s41564-024-01729-3","DOIUrl":"10.1038/s41564-024-01729-3","url":null,"abstract":"Swimming bacteria navigate chemical gradients using temporal sensing to detect changes in concentration over time. Here we show that surface-attached bacteria use a fundamentally different mode of sensing during chemotaxis. We combined microfluidic experiments, massively parallel cell tracking and fluorescent reporters to study how Pseudomonas aeruginosa senses chemical gradients during pili-based ‘twitching’ chemotaxis on surfaces. Unlike swimming cells, we found that temporal changes in concentration did not induce motility changes in twitching cells. We then quantified the chemotactic behaviour of stationary cells by following changes in the sub-cellular localization of fluorescent proteins as cells are exposed to a gradient that alternates direction. These experiments revealed that P. aeruginosa cells can directly sense differences in concentration across the lengths of their bodies, even in the presence of strong temporal fluctuations. Our work thus overturns the widely held notion that bacterial cells are too small to directly sense chemical gradients in space. Microfluidic experiments reveal that surface-attached Pseudomonas aeruginosa cells directly sense differences in chemical concentration across the length of their cell bodies to guide pili-based chemotaxis.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2308-2322"},"PeriodicalIF":20.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01729-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118126","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 : 2024-08-29DOI: 10.1038/s41564-024-01799-3
Vayu Maini Rekdal, José Manuel Villalobos-Escobedo, Nabila Rodriguez-Valeron, Mikel Olaizola Garcia, Diego Prado Vásquez, Alexander Rosales, Pia M. Sörensen, Edward E. K. Baidoo, Ana Calheiros de Carvalho, Robert Riley, Anna Lipzen, Guifen He, Mi Yan, Sajeet Haridas, Christopher Daum, Yuko Yoshinaga, Vivian Ng, Igor V. Grigoriev, Rasmus Munk, Christofora Hanny Wijaya, Lilis Nuraida, Isty Damayanti, Pablo Cruz-Morales, Jay. D. Keasling
Fungal fermentation of food and agricultural by-products holds promise for improving food sustainability and security. However, the molecular basis of fungal waste-to-food upcycling remains poorly understood. Here we use a multi-omics approach to characterize oncom, a fermented food traditionally produced from soymilk by-products in Java, Indonesia. Metagenomic sequencing of samples from small-scale producers in Western Java indicated that the fungus Neurospora intermedia dominates oncom. Further transcriptomic, metabolomic and phylogenomic analysis revealed that oncom-derived N. intermedia utilizes pectin and cellulose degradation during fermentation and belongs to a genetically distinct subpopulation associated with human-generated by-products. Finally, we found that N. intermedia grew on diverse by-products such as fruit and vegetable pomace and plant-based milk waste, did not encode mycotoxins, and could create foods that were positively perceived by consumers outside Indonesia. These results showcase the traditional significance and future potential of fungal fermentation for creating delicious and nutritious foods from readily available by-products. A multi-omics analysis of oncom, an Indonesian fermented food made from soymilk waste, shows how associated fungi break down food waste to yield nutritious and positively received foods.
真菌发酵食品和农副产品有望提高食品的可持续性和安全性。然而,人们对真菌废物转化为食品的分子基础仍然知之甚少。在这里,我们使用多组学方法来描述印尼爪哇传统上用豆浆副产品生产的发酵食品 oncom 的特征。对来自爪哇西部小规模生产者的样本进行的元基因组测序表明,Neurospora intermedia 真菌在 oncom 中占主导地位。进一步的转录组、代谢组和系统发生组分析表明,oncom 衍生的 N. intermedia 在发酵过程中利用果胶和纤维素降解,属于与人类产生的副产品相关的基因独特亚群。最后,我们发现 N. intermedia 可在多种副产品(如果蔬渣和植物性牛奶废料)上生长,不会产生霉菌毒素,并能制作出印尼以外消费者喜爱的食品。这些结果展示了真菌发酵的传统意义和未来潜力,即利用现成的副产品制作美味营养的食品。
{"title":"Neurospora intermedia from a traditional fermented food enables waste-to-food conversion","authors":"Vayu Maini Rekdal, José Manuel Villalobos-Escobedo, Nabila Rodriguez-Valeron, Mikel Olaizola Garcia, Diego Prado Vásquez, Alexander Rosales, Pia M. Sörensen, Edward E. K. Baidoo, Ana Calheiros de Carvalho, Robert Riley, Anna Lipzen, Guifen He, Mi Yan, Sajeet Haridas, Christopher Daum, Yuko Yoshinaga, Vivian Ng, Igor V. Grigoriev, Rasmus Munk, Christofora Hanny Wijaya, Lilis Nuraida, Isty Damayanti, Pablo Cruz-Morales, Jay. D. Keasling","doi":"10.1038/s41564-024-01799-3","DOIUrl":"10.1038/s41564-024-01799-3","url":null,"abstract":"Fungal fermentation of food and agricultural by-products holds promise for improving food sustainability and security. However, the molecular basis of fungal waste-to-food upcycling remains poorly understood. Here we use a multi-omics approach to characterize oncom, a fermented food traditionally produced from soymilk by-products in Java, Indonesia. Metagenomic sequencing of samples from small-scale producers in Western Java indicated that the fungus Neurospora intermedia dominates oncom. Further transcriptomic, metabolomic and phylogenomic analysis revealed that oncom-derived N. intermedia utilizes pectin and cellulose degradation during fermentation and belongs to a genetically distinct subpopulation associated with human-generated by-products. Finally, we found that N. intermedia grew on diverse by-products such as fruit and vegetable pomace and plant-based milk waste, did not encode mycotoxins, and could create foods that were positively perceived by consumers outside Indonesia. These results showcase the traditional significance and future potential of fungal fermentation for creating delicious and nutritious foods from readily available by-products. A multi-omics analysis of oncom, an Indonesian fermented food made from soymilk waste, shows how associated fungi break down food waste to yield nutritious and positively received foods.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 10","pages":"2666-2683"},"PeriodicalIF":20.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01799-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142089949","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}