Pub Date : 2024-10-16DOI: 10.1038/s41564-024-01848-x
Marya Getchell, Suci Wulandari, Ruklanthi de Alwis, Shreya Agoramurthy, Yoong Khean Khoo, Tze-Minn Mak, La Moe, Anne-Claire Stona, Junxiong Pang, Muhd Haziq Fikry Haji Abdul Momin, Afreenish Amir, Lucia Rizka Andalucia, Ghows Azzam, Savuth Chin, Thanat Chookajorn, Govindakarnavar Arunkumar, Do Thai Hung, Aamer Ikram, Runa Jha, Erik A. Karlsson, Mai Quynh Le Thi, Surakameth Mahasirimongkol, Gathsaurie Neelika Malavige, Jessica E. Manning, Syarifah Liza Munira, Nguyen Vu Trung, Imran Nisar, Firdausi Qadri, Farah Naz Qamar, Matthew T. Robinson, Cynthia P. Saloma, Swe Setk, Tahmina Shirin, Le Van Tan, Timothy John R. Dizon, Ravindran Thayan, Hlaing Myat Thu, Hasitha Tissera, Phonepadith Xangsayarath, Zainun Zaini, John C. W. Lim, Sebastian Maurer-Stroh, Gavin J. D. Smith, Lin-Fa Wang, Paul Pronyk
Correction to: Nature Microbiology https://doi.org/10.1038/s41564-024-01809-4, published online 24 September 2024.
{"title":"Author Correction: Pathogen genomic surveillance status among lower resource settings in Asia","authors":"Marya Getchell, Suci Wulandari, Ruklanthi de Alwis, Shreya Agoramurthy, Yoong Khean Khoo, Tze-Minn Mak, La Moe, Anne-Claire Stona, Junxiong Pang, Muhd Haziq Fikry Haji Abdul Momin, Afreenish Amir, Lucia Rizka Andalucia, Ghows Azzam, Savuth Chin, Thanat Chookajorn, Govindakarnavar Arunkumar, Do Thai Hung, Aamer Ikram, Runa Jha, Erik A. Karlsson, Mai Quynh Le Thi, Surakameth Mahasirimongkol, Gathsaurie Neelika Malavige, Jessica E. Manning, Syarifah Liza Munira, Nguyen Vu Trung, Imran Nisar, Firdausi Qadri, Farah Naz Qamar, Matthew T. Robinson, Cynthia P. Saloma, Swe Setk, Tahmina Shirin, Le Van Tan, Timothy John R. Dizon, Ravindran Thayan, Hlaing Myat Thu, Hasitha Tissera, Phonepadith Xangsayarath, Zainun Zaini, John C. W. Lim, Sebastian Maurer-Stroh, Gavin J. D. Smith, Lin-Fa Wang, Paul Pronyk","doi":"10.1038/s41564-024-01848-x","DOIUrl":"https://doi.org/10.1038/s41564-024-01848-x","url":null,"abstract":"<p>Correction to: <i>Nature Microbiology</i> https://doi.org/10.1038/s41564-024-01809-4, published online 24 September 2024.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"230 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439716","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 : 2024-10-16DOI: 10.1038/s41564-024-01823-6
Yutao Liu, Jialin Wu, Ruiying Liu, Fan Li, Leyan Xuan, Qian Wang, Dan Li, XinTong Chen, Hao Sun, Xiaoya Li, Chen Jin, Di Huang, Linxing Li, Guosheng Tang, Bin Liu
Vibrio cholerae causes cholera, an important cause of death worldwide. A fuller understanding of how virulence is regulated offers the potential for developing virulence inhibitors, regarded as efficient therapeutic alternatives for cholera treatment. Here we show using competitive infections of wild-type and mutant bacteria that the regulator of chitosan utilization, ChsR, increases V. cholerae virulence in vivo. Mechanistically, RNA sequencing, chromatin immunoprecipitation with sequencing and molecular biology approaches revealed that ChsR directly upregulated the expression of the virulence regulator, TcpP, which promoted expression of the cholera toxin and the toxin co-regulated pilus, in response to low O2 levels in the small intestine. We also found that chitosan degradation products inhibit the ChsR–tcpP promoter interaction. Consistently, administration of chitosan oligosaccharide, particularly when delivered via sodium alginate microsphere carriers, reduced V. cholerae intestinal colonization and disease severity in mice by blocking the chsR-mediated pathway. These data reveal the potential of chitosan oligosaccharide as supplemental therapy for cholera treatment and prevention. The chitosan utilization regulator, ChsR, positively regulates Vibrio cholerae virulence factor expression, which can be inhibited therapeutically by chitosan oligosaccharide administration in mice.
{"title":"Vibrio cholerae virulence is blocked by chitosan oligosaccharide-mediated inhibition of ChsR activity","authors":"Yutao Liu, Jialin Wu, Ruiying Liu, Fan Li, Leyan Xuan, Qian Wang, Dan Li, XinTong Chen, Hao Sun, Xiaoya Li, Chen Jin, Di Huang, Linxing Li, Guosheng Tang, Bin Liu","doi":"10.1038/s41564-024-01823-6","DOIUrl":"10.1038/s41564-024-01823-6","url":null,"abstract":"Vibrio cholerae causes cholera, an important cause of death worldwide. A fuller understanding of how virulence is regulated offers the potential for developing virulence inhibitors, regarded as efficient therapeutic alternatives for cholera treatment. Here we show using competitive infections of wild-type and mutant bacteria that the regulator of chitosan utilization, ChsR, increases V. cholerae virulence in vivo. Mechanistically, RNA sequencing, chromatin immunoprecipitation with sequencing and molecular biology approaches revealed that ChsR directly upregulated the expression of the virulence regulator, TcpP, which promoted expression of the cholera toxin and the toxin co-regulated pilus, in response to low O2 levels in the small intestine. We also found that chitosan degradation products inhibit the ChsR–tcpP promoter interaction. Consistently, administration of chitosan oligosaccharide, particularly when delivered via sodium alginate microsphere carriers, reduced V. cholerae intestinal colonization and disease severity in mice by blocking the chsR-mediated pathway. These data reveal the potential of chitosan oligosaccharide as supplemental therapy for cholera treatment and prevention. The chitosan utilization regulator, ChsR, positively regulates Vibrio cholerae virulence factor expression, which can be inhibited therapeutically by chitosan oligosaccharide administration in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2909-2922"},"PeriodicalIF":20.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Author Correction: Murine parainfluenza virus persists in lung innate immune cells sustaining chronic lung pathology","authors":"Ítalo Araújo Castro, Yanling Yang, Victoria Gnazzo, Do-Hyun Kim, Steven J. Van Dyken, Carolina B. López","doi":"10.1038/s41564-024-01852-1","DOIUrl":"https://doi.org/10.1038/s41564-024-01852-1","url":null,"abstract":"<p>Correction to: <i>Nature Microbiology</i> https://doi.org/10.1038/s41564-024-01805-8, published online 2 October 2024.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"1 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440576","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 : 2024-10-14DOI: 10.1038/s41564-024-01830-7
Arturo Vera-Ponce de León, Tim Hensen, Matthias Hoetzinger, Shashank Gupta, Bronson Weston, Sander M. Johnsen, Jacob A. Rasmussen, Cecilie Grønlund Clausen, Louisa Pless, Ana Raquel Andrade Veríssimo, Knut Rudi, Lars Snipen, Christian René Karlsen, Morten T. Limborg, Stefan Bertilsson, Ines Thiele, Torgeir R. Hvidsten, Simen R. Sandve, Phillip B. Pope, Sabina Leanti La Rosa
To ensure sustainable aquaculture, it is essential to understand the path ‘from feed to fish’, whereby the gut microbiome plays an important role in digestion and metabolism, ultimately influencing host health and growth. Previous work has reported the taxonomic composition of the Atlantic salmon (Salmo salar) gut microbiome; however, functional insights are lacking. Here we present the Salmon Microbial Genome Atlas consisting of 211 high-quality bacterial genomes, recovered by cultivation (n = 131) and gut metagenomics (n = 80) from wild and farmed fish both in freshwater and seawater. Bacterial genomes were taxonomically assigned to 14 different orders, including 35 distinctive genera and 29 previously undescribed species. Using metatranscriptomics, we functionally characterized key bacterial populations, across five phyla, in the salmon gut. This included the ability to degrade diet-derived fibres and release vitamins and other exometabolites with known beneficial effects, which was supported by genome-scale metabolic modelling and in vitro cultivation of selected bacterial species coupled with untargeted metabolomic studies. Together, the Salmon Microbial Genome Atlas provides a genomic and functional resource to enable future studies on salmon nutrition and health. Using shotgun metagenomics, cultivation and metabolic modelling, the authors construct the Salmon Microbial Genome Atlas as a resource for future studies on sustainable aquaculture.
{"title":"Genomic and functional characterization of the Atlantic salmon gut microbiome in relation to nutrition and health","authors":"Arturo Vera-Ponce de León, Tim Hensen, Matthias Hoetzinger, Shashank Gupta, Bronson Weston, Sander M. Johnsen, Jacob A. Rasmussen, Cecilie Grønlund Clausen, Louisa Pless, Ana Raquel Andrade Veríssimo, Knut Rudi, Lars Snipen, Christian René Karlsen, Morten T. Limborg, Stefan Bertilsson, Ines Thiele, Torgeir R. Hvidsten, Simen R. Sandve, Phillip B. Pope, Sabina Leanti La Rosa","doi":"10.1038/s41564-024-01830-7","DOIUrl":"10.1038/s41564-024-01830-7","url":null,"abstract":"To ensure sustainable aquaculture, it is essential to understand the path ‘from feed to fish’, whereby the gut microbiome plays an important role in digestion and metabolism, ultimately influencing host health and growth. Previous work has reported the taxonomic composition of the Atlantic salmon (Salmo salar) gut microbiome; however, functional insights are lacking. Here we present the Salmon Microbial Genome Atlas consisting of 211 high-quality bacterial genomes, recovered by cultivation (n = 131) and gut metagenomics (n = 80) from wild and farmed fish both in freshwater and seawater. Bacterial genomes were taxonomically assigned to 14 different orders, including 35 distinctive genera and 29 previously undescribed species. Using metatranscriptomics, we functionally characterized key bacterial populations, across five phyla, in the salmon gut. This included the ability to degrade diet-derived fibres and release vitamins and other exometabolites with known beneficial effects, which was supported by genome-scale metabolic modelling and in vitro cultivation of selected bacterial species coupled with untargeted metabolomic studies. Together, the Salmon Microbial Genome Atlas provides a genomic and functional resource to enable future studies on salmon nutrition and health. Using shotgun metagenomics, cultivation and metabolic modelling, the authors construct the Salmon Microbial Genome Atlas as a resource for future studies on sustainable aquaculture.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"3059-3074"},"PeriodicalIF":20.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431130","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 : 2024-10-10DOI: 10.1038/s41564-024-01835-2
Fernando Dias Gonçalves Lima, Mariano A. Molina
{"title":"Uncovering the HPV types causing cervical cancer","authors":"Fernando Dias Gonçalves Lima, Mariano A. Molina","doi":"10.1038/s41564-024-01835-2","DOIUrl":"10.1038/s41564-024-01835-2","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2795-2796"},"PeriodicalIF":20.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142397746","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 : 2024-10-08DOI: 10.1038/s41564-024-01819-2
Camille Bédard, Isabelle Gagnon-Arsenault, Jonathan Boisvert, Samuel Plante, Alexandre K. Dubé, Alicia Pageau, Anna Fijarczyk, Jehoshua Sharma, Laetitia Maroc, Rebecca S. Shapiro, Christian R. Landry
Azole antifungals are the main drugs used to treat fungal infections. Amino acid substitutions in the drug target Erg11 (Cyp51) are a common resistance mechanism in pathogenic yeasts. How many and which mutations confer resistance is, however, largely unknown. Here we measure the impact of nearly 4,000 amino acid variants of Candida albicans Erg11 on the susceptibility to six clinical azoles. This was achieved by deep mutational scanning of CaErg11 expressed in Saccharomyces cerevisiae. We find that a large fraction of mutations lead to resistance (33%), most resistance mutations confer cross-resistance (88%) and only a handful of resistance mutations show a significant fitness cost (9%). Our results reveal that resistance to azoles can arise through a large set of mutations and this will probably lead to azole pan-resistance, with little evolutionary compromise. This resource will help inform treatment choices in clinical settings and guide the development of new drugs. Deep mutational scanning of the azole antifungals drug target Erg11 provides an extensive catalogue of resistance mutations and reveals that resistance to azoles can arise through a large set of mutations that will probably lead to azole pan-resistance without a fitness cost.
{"title":"Most azole resistance mutations in the Candida albicans drug target confer cross-resistance without intrinsic fitness cost","authors":"Camille Bédard, Isabelle Gagnon-Arsenault, Jonathan Boisvert, Samuel Plante, Alexandre K. Dubé, Alicia Pageau, Anna Fijarczyk, Jehoshua Sharma, Laetitia Maroc, Rebecca S. Shapiro, Christian R. Landry","doi":"10.1038/s41564-024-01819-2","DOIUrl":"10.1038/s41564-024-01819-2","url":null,"abstract":"Azole antifungals are the main drugs used to treat fungal infections. Amino acid substitutions in the drug target Erg11 (Cyp51) are a common resistance mechanism in pathogenic yeasts. How many and which mutations confer resistance is, however, largely unknown. Here we measure the impact of nearly 4,000 amino acid variants of Candida albicans Erg11 on the susceptibility to six clinical azoles. This was achieved by deep mutational scanning of CaErg11 expressed in Saccharomyces cerevisiae. We find that a large fraction of mutations lead to resistance (33%), most resistance mutations confer cross-resistance (88%) and only a handful of resistance mutations show a significant fitness cost (9%). Our results reveal that resistance to azoles can arise through a large set of mutations and this will probably lead to azole pan-resistance, with little evolutionary compromise. This resource will help inform treatment choices in clinical settings and guide the development of new drugs. Deep mutational scanning of the azole antifungals drug target Erg11 provides an extensive catalogue of resistance mutations and reveals that resistance to azoles can arise through a large set of mutations that will probably lead to azole pan-resistance without a fitness cost.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"3025-3040"},"PeriodicalIF":20.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384363","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 : 2024-10-08DOI: 10.1038/s41564-024-01810-x
Ujjini H. Manjunatha, Suresh B. Lakshminarayana, Rajiv S. Jumani, Alexander T. Chao, Joseph M. Young, Jonathan E. Gable, Mark Knapp, Imad Hanna, Jean-Rene Galarneau, John Cantwell, Upendra Kulkarni, Michael Turner, Peichao Lu, Kristen H. Darrell, Lucy C. Watson, Katherine Chan, Debjani Patra, Mulugeta Mamo, Catherine Luu, Carlos Cuellar, Jacob Shaul, Linda Xiao, Ying-Bo Chen, Shannon K. Carney, Jay Lakshman, Colin S. Osborne, Jennifer A. Zambriski, Natasha Aziz, Christopher Sarko, Thierry T. Diagana
Diarrhoeal disease caused by Cryptosporidium is a major cause of morbidity and mortality in young and malnourished children from low- and middle-income countries, with no vaccine or effective treatment. Here we describe the discovery of EDI048, a Cryptosporidium PI(4)K inhibitor, designed to be active at the infection site in the gastrointestinal tract and undergo rapid metabolism in the liver. By using mutational analysis and crystal structure, we show that EDI048 binds to highly conserved amino acid residues in the ATP-binding site. EDI048 is orally efficacious in an immunocompromised mouse model despite negligible circulating concentrations, thus demonstrating that gastrointestinal exposure is necessary and sufficient for efficacy. In neonatal calves, a clinical model of cryptosporidiosis, EDI048 treatment resulted in rapid resolution of diarrhoea and significant reduction in faecal oocyst shedding. Safety and pharmacological studies demonstrated predictable metabolism and low systemic exposure of EDI048, providing a substantial safety margin required for a paediatric indication. EDI048 is a promising clinical candidate for the treatment of life-threatening paediatric cryptosporidiosis. EDI048 is a gastrointestinal-targeted Cryptosporidium PI(4)K inhibitor that undergoes a predictable metabolism and limits systemic exposure without compromising its anti-parasitic activity.
{"title":"Cryptosporidium PI(4)K inhibitor EDI048 is a gut-restricted parasiticidal agent to treat paediatric enteric cryptosporidiosis","authors":"Ujjini H. Manjunatha, Suresh B. Lakshminarayana, Rajiv S. Jumani, Alexander T. Chao, Joseph M. Young, Jonathan E. Gable, Mark Knapp, Imad Hanna, Jean-Rene Galarneau, John Cantwell, Upendra Kulkarni, Michael Turner, Peichao Lu, Kristen H. Darrell, Lucy C. Watson, Katherine Chan, Debjani Patra, Mulugeta Mamo, Catherine Luu, Carlos Cuellar, Jacob Shaul, Linda Xiao, Ying-Bo Chen, Shannon K. Carney, Jay Lakshman, Colin S. Osborne, Jennifer A. Zambriski, Natasha Aziz, Christopher Sarko, Thierry T. Diagana","doi":"10.1038/s41564-024-01810-x","DOIUrl":"10.1038/s41564-024-01810-x","url":null,"abstract":"Diarrhoeal disease caused by Cryptosporidium is a major cause of morbidity and mortality in young and malnourished children from low- and middle-income countries, with no vaccine or effective treatment. Here we describe the discovery of EDI048, a Cryptosporidium PI(4)K inhibitor, designed to be active at the infection site in the gastrointestinal tract and undergo rapid metabolism in the liver. By using mutational analysis and crystal structure, we show that EDI048 binds to highly conserved amino acid residues in the ATP-binding site. EDI048 is orally efficacious in an immunocompromised mouse model despite negligible circulating concentrations, thus demonstrating that gastrointestinal exposure is necessary and sufficient for efficacy. In neonatal calves, a clinical model of cryptosporidiosis, EDI048 treatment resulted in rapid resolution of diarrhoea and significant reduction in faecal oocyst shedding. Safety and pharmacological studies demonstrated predictable metabolism and low systemic exposure of EDI048, providing a substantial safety margin required for a paediatric indication. EDI048 is a promising clinical candidate for the treatment of life-threatening paediatric cryptosporidiosis. EDI048 is a gastrointestinal-targeted Cryptosporidium PI(4)K inhibitor that undergoes a predictable metabolism and limits systemic exposure without compromising its anti-parasitic activity.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2817-2835"},"PeriodicalIF":20.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01810-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384364","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 : 2024-10-03DOI: 10.1038/s41564-024-01806-7
Hannah L. Itell, Jamie Guenthoer, Daryl Humes, Nell E. Baumgarten, Julie Overbaugh
Human immunodeficiency virus type 1 (HIV-1) infection involves a selection bottleneck that leads to transmission of one or a few variants. C–C motif chemokine receptor 5 (CCR5) or C–X–C motif chemokine receptor 4 (CXCR4) can act as coreceptors for HIV-1 viral entry. However, initial infection mostly occurs via CCR5, despite abundant expression of CXCR4 on target cells. The host factors that influence HIV-1 susceptibility and selection during transmission are unclear. Here we conduct CRISPR–Cas9 screens and identify SLC35A2 (a transporter of UDP–galactose expressed in target cells in blood and mucosa) as a potent and specific CXCR4-tropic restriction factor in primary target CD4+ T cells. SLC35A2 inactivation, which resulted in truncated glycans, not only increased CXCR4-tropic infection levels but also decreased those of CCR5-tropic strains consistently. Single-cycle infections demonstrated that the effect is cell-intrinsic. These data support a role for a host protein that influences glycan structure in regulating HIV-1 infection. Host cell glycosylation may, therefore, affect HIV-1 selection during transmission in vivo. CRISPR–Cas9 screens in primary CD4+ T cells enable identification of SLC35A2 as a host factor that restricts CXCR4-tropic HIV-1 viral entry and promotes that of CCR5-tropic viruses.
{"title":"Host cell glycosylation selects for infection with CCR5- versus CXCR4-tropic HIV-1","authors":"Hannah L. Itell, Jamie Guenthoer, Daryl Humes, Nell E. Baumgarten, Julie Overbaugh","doi":"10.1038/s41564-024-01806-7","DOIUrl":"10.1038/s41564-024-01806-7","url":null,"abstract":"Human immunodeficiency virus type 1 (HIV-1) infection involves a selection bottleneck that leads to transmission of one or a few variants. C–C motif chemokine receptor 5 (CCR5) or C–X–C motif chemokine receptor 4 (CXCR4) can act as coreceptors for HIV-1 viral entry. However, initial infection mostly occurs via CCR5, despite abundant expression of CXCR4 on target cells. The host factors that influence HIV-1 susceptibility and selection during transmission are unclear. Here we conduct CRISPR–Cas9 screens and identify SLC35A2 (a transporter of UDP–galactose expressed in target cells in blood and mucosa) as a potent and specific CXCR4-tropic restriction factor in primary target CD4+ T cells. SLC35A2 inactivation, which resulted in truncated glycans, not only increased CXCR4-tropic infection levels but also decreased those of CCR5-tropic strains consistently. Single-cycle infections demonstrated that the effect is cell-intrinsic. These data support a role for a host protein that influences glycan structure in regulating HIV-1 infection. Host cell glycosylation may, therefore, affect HIV-1 selection during transmission in vivo. CRISPR–Cas9 screens in primary CD4+ T cells enable identification of SLC35A2 as a host factor that restricts CXCR4-tropic HIV-1 viral entry and promotes that of CCR5-tropic viruses.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2985-2996"},"PeriodicalIF":20.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369113","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 : 2024-10-02DOI: 10.1038/s41564-024-01805-8
Ítalo Araújo Castro, Yanling Yang, Victoria Gnazzo, Do-Hyun Kim, Steven J. Van Dyken, Carolina B. López
Common respiratory viruses, including the human parainfluenza viruses, threaten human health seasonally and associate with the development of chronic lung diseases. Evidence suggests that these viruses can persist, but the sources of viral products in vivo and their impact on chronic respiratory diseases remain unknown. Using the murine parainfluenza virus Sendai, we demonstrate that viral protein and RNA persist in lung macrophages, type 2 innate lymphoid cells (ILC2s) and dendritic cells long after the infectious virus is cleared. Cells containing persistent viral protein expressed Th2 inflammation-related transcriptomic signatures associated with the development of chronic lung diseases, including asthma. Lineage tracing demonstrated that distinct functional groups of cells contribute to the chronic pathology. Importantly, targeted ablation of infected cells significantly ameliorated chronic lung disease. Overall, we identified persistent infection of innate immune cells as a key factor in the progression from acute to chronic lung disease after infection with parainfluenza virus. Murine parainfluenza virus (Sendai) persists and imprints lung innate immune cells, leaving long-lasting transcriptomic alterations associated with type-2 inflammation and development of chronic lung diseases.
{"title":"Murine parainfluenza virus persists in lung innate immune cells sustaining chronic lung pathology","authors":"Ítalo Araújo Castro, Yanling Yang, Victoria Gnazzo, Do-Hyun Kim, Steven J. Van Dyken, Carolina B. López","doi":"10.1038/s41564-024-01805-8","DOIUrl":"10.1038/s41564-024-01805-8","url":null,"abstract":"Common respiratory viruses, including the human parainfluenza viruses, threaten human health seasonally and associate with the development of chronic lung diseases. Evidence suggests that these viruses can persist, but the sources of viral products in vivo and their impact on chronic respiratory diseases remain unknown. Using the murine parainfluenza virus Sendai, we demonstrate that viral protein and RNA persist in lung macrophages, type 2 innate lymphoid cells (ILC2s) and dendritic cells long after the infectious virus is cleared. Cells containing persistent viral protein expressed Th2 inflammation-related transcriptomic signatures associated with the development of chronic lung diseases, including asthma. Lineage tracing demonstrated that distinct functional groups of cells contribute to the chronic pathology. Importantly, targeted ablation of infected cells significantly ameliorated chronic lung disease. Overall, we identified persistent infection of innate immune cells as a key factor in the progression from acute to chronic lung disease after infection with parainfluenza virus. Murine parainfluenza virus (Sendai) persists and imprints lung innate immune cells, leaving long-lasting transcriptomic alterations associated with type-2 inflammation and development of chronic lung diseases.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2803-2816"},"PeriodicalIF":20.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362741","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 : 2024-10-01DOI: 10.1038/s41564-024-01800-z
Viviana Freire-Zapata, Hannah Holland-Moritz, Dylan R. Cronin, Sam Aroney, Derek A. Smith, Rachel M. Wilson, Jessica G. Ernakovich, Ben J. Woodcroft, Sarah C. Bagby, EMERGE 2012 Field Team, EMERGE Biology Integration Coordinators, Virginia I. Rich, Matthew B. Sullivan, James C. Stegen, Malak M. Tfaily
Interactions between microbiomes and metabolites play crucial roles in the environment, yet how these interactions drive greenhouse gas emissions during ecosystem changes remains unclear. Here we analysed microbial and metabolite composition across a permafrost thaw gradient in Stordalen Mire, Sweden, using paired genome-resolved metagenomics and high-resolution Fourier transform ion cyclotron resonance mass spectrometry guided by principles from community assembly theory to test whether microorganisms and metabolites show concordant responses to changing drivers. Our analysis revealed divergence between the inferred microbial versus metabolite assembly processes, suggesting distinct responses to the same selective pressures. This contradicts common assumptions in trait-based microbial models and highlights the limitations of measuring microbial community-level data alone. Furthermore, feature-scale analysis revealed connections between microbial taxa, metabolites and observed CO2 and CH4 porewater variations. Our study showcases insights gained by using feature-level data and microorganism–metabolite interactions to better understand metabolic processes that drive greenhouse gas emissions during ecosystem changes. A multi-omics investigation at Sweden’s Stordalen Mire shows that microbial dynamics and metabolites must be taken into account to predict ecosystem responses to environmental change.
微生物组和代谢物之间的相互作用在环境中起着至关重要的作用，但这些相互作用如何在生态系统变化过程中推动温室气体排放仍不清楚。在这里，我们以群落组装理论为指导，利用成对的基因组分辨元基因组学和高分辨率傅立叶变换离子回旋共振质谱分析了瑞典 Stordalen Mire 永久冻土融化梯度上的微生物和代谢物组成，以检验微生物和代谢物是否对不断变化的驱动因素表现出一致的反应。我们的分析表明，推断出的微生物与代谢物组装过程之间存在差异，这表明它们对相同的选择性压力做出了不同的反应。这与基于性状的微生物模型中的常见假设相矛盾，并凸显了仅测量微生物群落级数据的局限性。此外，特征尺度分析揭示了微生物类群、代谢物与观测到的二氧化碳和甲烷孔隙水变化之间的联系。我们的研究展示了利用特征级数据和微生物与代谢物之间的相互作用来更好地理解生态系统变化过程中驱动温室气体排放的代谢过程所获得的洞察力。
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