Pub Date : 2024-10-30DOI: 10.1038/s41564-024-01838-z
Jane E. Sinclair, Courtney Vedelago, Feargal J. Ryan, Meagan Carney, Meredith A. Redd, Miriam A. Lynn, Branka Grubor-Bauk, Yuanzhao Cao, Anjali K. Henders, Keng Yih Chew, Deborah Gilroy, Kim Greaves, Larisa Labzin, Laura Ziser, Katharina Ronacher, Leanne M. Wallace, Yiwen Zhang, Kyle Macauslane, Daniel J. Ellis, Sudha Rao, Lucy Burr, Amanda Bain, Anjana Karawita, Benjamin L. Schulz, Junrong Li, David J. Lynn, Nathan Palpant, Alain Wuethrich, Matt Trau, Kirsty R. Short
An estimated 65 million people globally suffer from post-acute sequelae of COVID-19 (PASC), with many experiencing cardiovascular symptoms (PASC-CVS) like chest pain and heart palpitations. This study examines the role of chronic inflammation in PASC-CVS, particularly in individuals with symptoms persisting over a year after infection. Blood samples from three groups—recovered individuals, those with prolonged PASC-CVS and SARS-CoV-2-negative individuals—revealed that those with PASC-CVS had a blood signature linked to inflammation. Trace-level pro-inflammatory cytokines were detected in the plasma from donors with PASC-CVS 18 months post infection using nanotechnology. Importantly, these trace-level cytokines affected the function of primary human cardiomyocytes. Plasma proteomics also demonstrated higher levels of complement and coagulation proteins in the plasma from patients with PASC-CVS. This study highlights chronic inflammation’s role in the symptoms of PASC-CVS.
{"title":"Post-acute sequelae of SARS-CoV-2 cardiovascular symptoms are associated with trace-level cytokines that affect cardiomyocyte function","authors":"Jane E. Sinclair, Courtney Vedelago, Feargal J. Ryan, Meagan Carney, Meredith A. Redd, Miriam A. Lynn, Branka Grubor-Bauk, Yuanzhao Cao, Anjali K. Henders, Keng Yih Chew, Deborah Gilroy, Kim Greaves, Larisa Labzin, Laura Ziser, Katharina Ronacher, Leanne M. Wallace, Yiwen Zhang, Kyle Macauslane, Daniel J. Ellis, Sudha Rao, Lucy Burr, Amanda Bain, Anjana Karawita, Benjamin L. Schulz, Junrong Li, David J. Lynn, Nathan Palpant, Alain Wuethrich, Matt Trau, Kirsty R. Short","doi":"10.1038/s41564-024-01838-z","DOIUrl":"https://doi.org/10.1038/s41564-024-01838-z","url":null,"abstract":"<p>An estimated 65 million people globally suffer from post-acute sequelae of COVID-19 (PASC), with many experiencing cardiovascular symptoms (PASC-CVS) like chest pain and heart palpitations. This study examines the role of chronic inflammation in PASC-CVS, particularly in individuals with symptoms persisting over a year after infection. Blood samples from three groups—recovered individuals, those with prolonged PASC-CVS and SARS-CoV-2-negative individuals—revealed that those with PASC-CVS had a blood signature linked to inflammation. Trace-level pro-inflammatory cytokines were detected in the plasma from donors with PASC-CVS 18 months post infection using nanotechnology. Importantly, these trace-level cytokines affected the function of primary human cardiomyocytes. Plasma proteomics also demonstrated higher levels of complement and coagulation proteins in the plasma from patients with PASC-CVS. This study highlights chronic inflammation’s role in the symptoms of PASC-CVS.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"126 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536902","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 : 2024-10-30DOI: 10.1038/s41564-024-01827-2
Elijah C. Mehlferber, Gontran Arnault, Bishnu Joshi, Laila P. Partida-Martinez, Kathryn A. Patras, Marie Simonin, Britt Koskella
The design and use of synthetic communities, or SynComs, is one of the most promising strategies for disentangling the complex interactions within microbial communities, and between these communities and their hosts. Compared to natural communities, these simplified consortia provide the opportunity to study ecological interactions at tractable scales, as well as facilitating reproducibility and fostering interdisciplinary science. However, the effective implementation of the SynCom approach requires several important considerations regarding the development and application of these model systems. There are also emerging ethical considerations when both designing and deploying SynComs in clinical, agricultural or environmental settings. Here we outline current best practices in developing, implementing and evaluating SynComs across different systems, including a focus on important ethical considerations for SynCom research. Here the authors outline best practices for the development, implementation and evaluation of synthetic microbial communities (or SynComs) across different systems.
{"title":"A cross-systems primer for synthetic microbial communities","authors":"Elijah C. Mehlferber, Gontran Arnault, Bishnu Joshi, Laila P. Partida-Martinez, Kathryn A. Patras, Marie Simonin, Britt Koskella","doi":"10.1038/s41564-024-01827-2","DOIUrl":"10.1038/s41564-024-01827-2","url":null,"abstract":"The design and use of synthetic communities, or SynComs, is one of the most promising strategies for disentangling the complex interactions within microbial communities, and between these communities and their hosts. Compared to natural communities, these simplified consortia provide the opportunity to study ecological interactions at tractable scales, as well as facilitating reproducibility and fostering interdisciplinary science. However, the effective implementation of the SynCom approach requires several important considerations regarding the development and application of these model systems. There are also emerging ethical considerations when both designing and deploying SynComs in clinical, agricultural or environmental settings. Here we outline current best practices in developing, implementing and evaluating SynComs across different systems, including a focus on important ethical considerations for SynCom research. Here the authors outline best practices for the development, implementation and evaluation of synthetic microbial communities (or SynComs) across different systems.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2765-2773"},"PeriodicalIF":20.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541486","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 : 2024-10-30DOI: 10.1038/s41564-024-01833-4
Trent R. Northen, Manuel Kleiner, Marta Torres, Ákos T. Kovács, Mette Haubjerg Nicolaisen, Dorota M. Krzyżanowska, Shilpi Sharma, George Lund, Lars Jelsbak, Oliver Baars, Nikolaj Lunding Kindtler, Kathrin Wippel, Caja Dinesen, Jessica A. Ferrarezi, Malek Marian, Adele Pioppi, Xinming Xu, Tonni Andersen, Niko Geldner, Paul Schulze-Lefert, Julia A. Vorholt, Ruben Garrido-Oter
Harnessing beneficial microorganisms is seen as a promising approach to enhance sustainable agriculture production. Synthetic communities (SynComs) are increasingly being used to study relevant microbial activities and interactions with the plant host. Yet, the lack of community standards limits the efficiency and progress in this important area of research. To address this gap, we recommend three actions: (1) defining reference SynComs; (2) establishing community standards, protocols and benchmark data for constructing and using SynComs; and (3) creating an infrastructure for sharing strains and data. We also outline opportunities to develop SynCom research through technical advances, linking to field studies, and filling taxonomic blind spots to move towards fully representative SynComs. Here the authors discuss the use of synthetic communities, or SynComs, in plant–microbiome research and propose steps to develop community standards that will support future research.
{"title":"Community standards and future opportunities for synthetic communities in plant–microbiota research","authors":"Trent R. Northen, Manuel Kleiner, Marta Torres, Ákos T. Kovács, Mette Haubjerg Nicolaisen, Dorota M. Krzyżanowska, Shilpi Sharma, George Lund, Lars Jelsbak, Oliver Baars, Nikolaj Lunding Kindtler, Kathrin Wippel, Caja Dinesen, Jessica A. Ferrarezi, Malek Marian, Adele Pioppi, Xinming Xu, Tonni Andersen, Niko Geldner, Paul Schulze-Lefert, Julia A. Vorholt, Ruben Garrido-Oter","doi":"10.1038/s41564-024-01833-4","DOIUrl":"10.1038/s41564-024-01833-4","url":null,"abstract":"Harnessing beneficial microorganisms is seen as a promising approach to enhance sustainable agriculture production. Synthetic communities (SynComs) are increasingly being used to study relevant microbial activities and interactions with the plant host. Yet, the lack of community standards limits the efficiency and progress in this important area of research. To address this gap, we recommend three actions: (1) defining reference SynComs; (2) establishing community standards, protocols and benchmark data for constructing and using SynComs; and (3) creating an infrastructure for sharing strains and data. We also outline opportunities to develop SynCom research through technical advances, linking to field studies, and filling taxonomic blind spots to move towards fully representative SynComs. Here the authors discuss the use of synthetic communities, or SynComs, in plant–microbiome research and propose steps to develop community standards that will support future research.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2774-2784"},"PeriodicalIF":20.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541482","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 : 2024-10-30DOI: 10.1038/s41564-024-01831-6
Kevin Whelan, Margaret Alexander, Claire Gaiani, Genelle Lunken, Andrew Holmes, Heidi M. Staudacher, Stephan Theis, Maria L. Marco
Diet is a major determinant of the gastrointestinal microbiome composition and function, yet our understanding of how it impacts the efficacy of prebiotics and probiotics is limited. Here we examine current evidence of dietary influence on prebiotic and probiotic efficacy in human studies, including potential mechanisms. We propose that habitual diet be included as a variable in prebiotic and probiotic intervention studies. This recommendation is based on the potential mechanisms via which diet can affect study outcomes, either directly or through the gut microbiome. We consider the challenges and opportunities of dietary assessment in this context. Lastly, we provide recommendations for the design, conduct and reporting of human clinical trials of prebiotics and probiotics (and other biotic interventions) to account for any effect of diet and nutrition. Here the authors make recommendations for the design of clinical trials for prebiotics and probiotics that includes consideration of diet and the gut microbiome.
{"title":"Design and reporting of prebiotic and probiotic clinical trials in the context of diet and the gut microbiome","authors":"Kevin Whelan, Margaret Alexander, Claire Gaiani, Genelle Lunken, Andrew Holmes, Heidi M. Staudacher, Stephan Theis, Maria L. Marco","doi":"10.1038/s41564-024-01831-6","DOIUrl":"10.1038/s41564-024-01831-6","url":null,"abstract":"Diet is a major determinant of the gastrointestinal microbiome composition and function, yet our understanding of how it impacts the efficacy of prebiotics and probiotics is limited. Here we examine current evidence of dietary influence on prebiotic and probiotic efficacy in human studies, including potential mechanisms. We propose that habitual diet be included as a variable in prebiotic and probiotic intervention studies. This recommendation is based on the potential mechanisms via which diet can affect study outcomes, either directly or through the gut microbiome. We consider the challenges and opportunities of dietary assessment in this context. Lastly, we provide recommendations for the design, conduct and reporting of human clinical trials of prebiotics and probiotics (and other biotic interventions) to account for any effect of diet and nutrition. Here the authors make recommendations for the design of clinical trials for prebiotics and probiotics that includes consideration of diet and the gut microbiome.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2785-2794"},"PeriodicalIF":20.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541483","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 : 2024-10-29DOI: 10.1038/s41564-024-01811-w
Hans Carolus, Dimitrios Sofras, Giorgio Boccarella, Stef Jacobs, Vladislav Biriukov, Louise Goossens, Alicia Chen, Ina Vantyghem, Tibo Verbeeck, Siebe Pierson, Celia Lobo Romero, Hans Steenackers, Katrien Lagrou, Pieter van den Berg, Judith Berman, Toni Gabaldón, Patrick Van Dijck
Antifungal drug resistance represents a serious global health threat, necessitating new treatment strategies. Here we investigated collateral sensitivity (CS), in which resistance to one drug increases sensitivity to another, and cross-resistance (XR), in which one drug resistance mechanism reduces susceptibility to multiple drugs, since CS and XR dynamics can guide treatment design to impede resistance development, but have not been systematically explored in pathogenic fungi. We used experimental evolution and mathematical modelling of Candida auris population dynamics during cyclic and combined drug exposures and found that especially CS-based drug cycling can effectively prevent the emergence of drug resistance. In addition, we found that a CS-based treatment switch can actively select against or eradicate resistant sub-populations, highlighting the potential to consider CS in therapeutic decision-making upon resistance detection. Furthermore, we show that some CS trends are robust among different strains and resistance mechanisms. Overall, these findings provide a promising direction for improved antifungal treatment approaches. Collateral-sensitivity-based drug cycling effectively prevents and impedes the evolution of antifungal drug resistance in Candida auris.
{"title":"Collateral sensitivity counteracts the evolution of antifungal drug resistance in Candida auris","authors":"Hans Carolus, Dimitrios Sofras, Giorgio Boccarella, Stef Jacobs, Vladislav Biriukov, Louise Goossens, Alicia Chen, Ina Vantyghem, Tibo Verbeeck, Siebe Pierson, Celia Lobo Romero, Hans Steenackers, Katrien Lagrou, Pieter van den Berg, Judith Berman, Toni Gabaldón, Patrick Van Dijck","doi":"10.1038/s41564-024-01811-w","DOIUrl":"10.1038/s41564-024-01811-w","url":null,"abstract":"Antifungal drug resistance represents a serious global health threat, necessitating new treatment strategies. Here we investigated collateral sensitivity (CS), in which resistance to one drug increases sensitivity to another, and cross-resistance (XR), in which one drug resistance mechanism reduces susceptibility to multiple drugs, since CS and XR dynamics can guide treatment design to impede resistance development, but have not been systematically explored in pathogenic fungi. We used experimental evolution and mathematical modelling of Candida auris population dynamics during cyclic and combined drug exposures and found that especially CS-based drug cycling can effectively prevent the emergence of drug resistance. In addition, we found that a CS-based treatment switch can actively select against or eradicate resistant sub-populations, highlighting the potential to consider CS in therapeutic decision-making upon resistance detection. Furthermore, we show that some CS trends are robust among different strains and resistance mechanisms. Overall, these findings provide a promising direction for improved antifungal treatment approaches. Collateral-sensitivity-based drug cycling effectively prevents and impedes the evolution of antifungal drug resistance in Candida auris.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2954-2969"},"PeriodicalIF":20.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520171","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 : 2024-10-28DOI: 10.1038/s41564-024-01837-0
Keng Yih Chew, Kirsty R. Short
Viral RNA and protein are found to persist in infected lungs and contribute to post-acute pathology in Sendai virus infection.
发现病毒 RNA 和蛋白质会在受感染的肺部持续存在,并导致仙台病毒感染后的急性病理变化。
{"title":"Persistent viral RNA and protein contribute to post-acute pathology","authors":"Keng Yih Chew, Kirsty R. Short","doi":"10.1038/s41564-024-01837-0","DOIUrl":"10.1038/s41564-024-01837-0","url":null,"abstract":"Viral RNA and protein are found to persist in infected lungs and contribute to post-acute pathology in Sendai virus infection.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2797-2798"},"PeriodicalIF":20.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519210","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 : 2024-10-28DOI: 10.1038/s41564-024-01836-1
Lorenz Leitner, Shawna McCallin
Integrating global and local genomic surveillance into phage therapy cocktail design offers a middle ground between personalized and product-based treatment options.
{"title":"Guiding phage therapy with genomic surveillance","authors":"Lorenz Leitner, Shawna McCallin","doi":"10.1038/s41564-024-01836-1","DOIUrl":"10.1038/s41564-024-01836-1","url":null,"abstract":"Integrating global and local genomic surveillance into phage therapy cocktail design offers a middle ground between personalized and product-based treatment options.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2799-2800"},"PeriodicalIF":20.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519244","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 : 2024-10-28DOI: 10.1038/s41564-024-01821-8
Félix Ramos-León, Brandon R. Anjuwon-Foster, Vivek Anantharaman, Taylor B. Updegrove, Colby N. Ferreira, Amany M. Ibrahim, Chin-Hsien Tai, Michael J. Kruhlak, Dominique M. Missiakas, Jodi L. Camberg, L. Aravind, Kumaran S. Ramamurthi
The bacterial pathogen, Staphylococcus aureus, grows by dividing in two alternating orthogonal planes. How these cell division planes are positioned correctly is not known. Here we used chemical genetic screening to identify PcdA as a division plane placement factor. Molecular biology and imaging approaches revealed non-orthogonal division plane selection for pcdA mutant bacteria. PcdA is a structurally and functionally altered member of the McrB AAA+ NTPase family, which are often found as restriction enzyme subunits. PcdA interacts with the tubulin-like divisome component, FtsZ, and the structural protein, DivIVA; it also localizes to future cell division sites. PcdA multimerization, localization and function are NTPase activity-dependent. We propose that the DivIVA/PcdA complex recruits unpolymerized FtsZ to assemble along the proper cell division plane. Although pcdA deletion did not affect S. aureus growth in several laboratory conditions, its clustered growth pattern was disrupted, sensitivity to cell-wall-targeting antibiotics increased and virulence in mice decreased. We propose that the characteristic clustered growth pattern of S. aureus, which emerges from dividing in alternating orthogonal division planes, might protect the bacterium from host defences. PcdA interacts with DivIVA and FtsZ, promoting Z-ring formation and division plane selection in Staphylococcus aureus, which increases virulence in mice and reduces sensitivity to cell-wall-targeting antibiotics.
{"title":"PcdA promotes orthogonal division plane selection in Staphylococcus aureus","authors":"Félix Ramos-León, Brandon R. Anjuwon-Foster, Vivek Anantharaman, Taylor B. Updegrove, Colby N. Ferreira, Amany M. Ibrahim, Chin-Hsien Tai, Michael J. Kruhlak, Dominique M. Missiakas, Jodi L. Camberg, L. Aravind, Kumaran S. Ramamurthi","doi":"10.1038/s41564-024-01821-8","DOIUrl":"10.1038/s41564-024-01821-8","url":null,"abstract":"The bacterial pathogen, Staphylococcus aureus, grows by dividing in two alternating orthogonal planes. How these cell division planes are positioned correctly is not known. Here we used chemical genetic screening to identify PcdA as a division plane placement factor. Molecular biology and imaging approaches revealed non-orthogonal division plane selection for pcdA mutant bacteria. PcdA is a structurally and functionally altered member of the McrB AAA+ NTPase family, which are often found as restriction enzyme subunits. PcdA interacts with the tubulin-like divisome component, FtsZ, and the structural protein, DivIVA; it also localizes to future cell division sites. PcdA multimerization, localization and function are NTPase activity-dependent. We propose that the DivIVA/PcdA complex recruits unpolymerized FtsZ to assemble along the proper cell division plane. Although pcdA deletion did not affect S. aureus growth in several laboratory conditions, its clustered growth pattern was disrupted, sensitivity to cell-wall-targeting antibiotics increased and virulence in mice decreased. We propose that the characteristic clustered growth pattern of S. aureus, which emerges from dividing in alternating orthogonal division planes, might protect the bacterium from host defences. PcdA interacts with DivIVA and FtsZ, promoting Z-ring formation and division plane selection in Staphylococcus aureus, which increases virulence in mice and reduces sensitivity to cell-wall-targeting antibiotics.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2997-3012"},"PeriodicalIF":20.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519237","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 : 2024-10-25DOI: 10.1038/s41564-024-01842-3
Lucas A. Meirelles, Evangelia Vayena, Auriane Debache, Eric Schmidt, Tamara Rossy, Tania Distler, Vassily Hatzimanikatis, Alexandre Persat
Pseudomonas aeruginosa frequently causes antibiotic-recalcitrant pneumonia, but the mechanisms driving its adaptation during human infections remain unclear. To reveal the selective pressures and adaptation strategies at the mucosal surface, here we investigated P. aeruginosa growth and antibiotic tolerance in tissue-engineered airways by transposon insertion sequencing (Tn-seq). Metabolic modelling based on Tn-seq data revealed the nutritional requirements for P. aeruginosa growth, highlighting reliance on glucose and lactate and varying requirements for amino acid biosynthesis. Tn-seq also revealed selection against biofilm formation during mucosal growth in the absence of antibiotics. Live imaging in engineered organoids showed that biofilm-dwelling cells remained sessile while colonizing the mucosal surface, limiting nutrient foraging and reduced growth. Conversely, biofilm formation increased antibiotic tolerance at the mucosal surface. Moreover, mutants with exacerbated biofilm phenotypes protected less tolerant but more cytotoxic strains, contributing to phenotypic heterogeneity. P. aeruginosa must therefore navigate conflicting physical and biological selective pressures to establish chronic infections.
{"title":"Pseudomonas aeruginosa faces a fitness trade-off between mucosal colonization and antibiotic tolerance during airway infection","authors":"Lucas A. Meirelles, Evangelia Vayena, Auriane Debache, Eric Schmidt, Tamara Rossy, Tania Distler, Vassily Hatzimanikatis, Alexandre Persat","doi":"10.1038/s41564-024-01842-3","DOIUrl":"https://doi.org/10.1038/s41564-024-01842-3","url":null,"abstract":"<p><i>Pseudomonas aeruginosa</i> frequently causes antibiotic-recalcitrant pneumonia, but the mechanisms driving its adaptation during human infections remain unclear. To reveal the selective pressures and adaptation strategies at the mucosal surface, here we investigated <i>P. aeruginosa</i> growth and antibiotic tolerance in tissue-engineered airways by transposon insertion sequencing (Tn-seq). Metabolic modelling based on Tn-seq data revealed the nutritional requirements for <i>P. aeruginosa</i> growth, highlighting reliance on glucose and lactate and varying requirements for amino acid biosynthesis. Tn-seq also revealed selection against biofilm formation during mucosal growth in the absence of antibiotics. Live imaging in engineered organoids showed that biofilm-dwelling cells remained sessile while colonizing the mucosal surface, limiting nutrient foraging and reduced growth. Conversely, biofilm formation increased antibiotic tolerance at the mucosal surface. Moreover, mutants with exacerbated biofilm phenotypes protected less tolerant but more cytotoxic strains, contributing to phenotypic heterogeneity. <i>P. aeruginosa</i> must therefore navigate conflicting physical and biological selective pressures to establish chronic infections.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"97 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489431","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 : 2024-10-24DOI: 10.1038/s41564-024-01839-y
Zongzhi Wu, Shufeng Liu, Jinren Ni
The archaeal superphylum DPANN (an acronym formed from the initials of the first five phyla discovered: Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanohaloarchaeota and Nanoarchaeota) is a group of ultrasmall symbionts able to survive in extreme ecosystems. The diversity and dynamics between DPANN archaea and their virome remain largely unknown. Here we use a metagenomic clustered regularly interspaced short palindromic repeats (CRISPR) screening approach to identify 97 globally distributed, non-redundant viruses and unclassified mobile genetic elements predicted to infect hosts across 8 DPANN phyla, including 7 viral groups not previously characterized. Genomic analysis suggests a diversity of viral morphologies including head-tailed, tailless icosahedral and spindle-shaped viruses with the potential to establish lytic, chronic or lysogenic infections. We also find evidence of a virally encoded Cas12f1 protein (probably originating from uncultured DPANN archaea) and a mini-CRISPR array, which could play a role in modulating host metabolism. Many metagenomes have virus-to-host ratios >10, indicating that DPANN viruses play an important role in controlling host populations. Overall, our study illuminates the underexplored diversity, functional repertoires and host interactions of the DPANN virome.
{"title":"Metagenomic characterization of viruses and mobile genetic elements associated with the DPANN archaeal superphylum","authors":"Zongzhi Wu, Shufeng Liu, Jinren Ni","doi":"10.1038/s41564-024-01839-y","DOIUrl":"https://doi.org/10.1038/s41564-024-01839-y","url":null,"abstract":"<p>The archaeal superphylum DPANN (an acronym formed from the initials of the first five phyla discovered: Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanohaloarchaeota and Nanoarchaeota) is a group of ultrasmall symbionts able to survive in extreme ecosystems. The diversity and dynamics between DPANN archaea and their virome remain largely unknown. Here we use a metagenomic clustered regularly interspaced short palindromic repeats (CRISPR) screening approach to identify 97 globally distributed, non-redundant viruses and unclassified mobile genetic elements predicted to infect hosts across 8 DPANN phyla, including 7 viral groups not previously characterized. Genomic analysis suggests a diversity of viral morphologies including head-tailed, tailless icosahedral and spindle-shaped viruses with the potential to establish lytic, chronic or lysogenic infections. We also find evidence of a virally encoded Cas12f1 protein (probably originating from uncultured DPANN archaea) and a mini-CRISPR array, which could play a role in modulating host metabolism. Many metagenomes have virus-to-host ratios >10, indicating that DPANN viruses play an important role in controlling host populations. Overall, our study illuminates the underexplored diversity, functional repertoires and host interactions of the DPANN virome.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"56 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489009","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}