NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections
Abstract Lower respiratory tract infections caused by Streptococcus pneumoniae (Spn) are a leading cause of death globally. Here we investigate the bronchial epithelial cellular response to Spn infection on a transcriptomic, proteomic and metabolic level. We found the NAD+ salvage pathway to be dysr...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41372-w |
| _version_ | 1827710150395297792 |
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| author | Björn Klabunde André Wesener Wilhelm Bertrams Isabell Beinborn Nicole Paczia Kristin Surmann Sascha Blankenburg Jochen Wilhelm Javier Serrania Kèvin Knoops Eslam M. Elsayed Katrin Laakmann Anna Lena Jung Andreas Kirschbaum Sven Hammerschmidt Belal Alshaar Nicolas Gisch Mobarak Abu Mraheil Anke Becker Uwe Völker Evelyn Vollmeister Birke J. Benedikter Bernd Schmeck |
| author_facet | Björn Klabunde André Wesener Wilhelm Bertrams Isabell Beinborn Nicole Paczia Kristin Surmann Sascha Blankenburg Jochen Wilhelm Javier Serrania Kèvin Knoops Eslam M. Elsayed Katrin Laakmann Anna Lena Jung Andreas Kirschbaum Sven Hammerschmidt Belal Alshaar Nicolas Gisch Mobarak Abu Mraheil Anke Becker Uwe Völker Evelyn Vollmeister Birke J. Benedikter Bernd Schmeck |
| author_sort | Björn Klabunde |
| collection | DOAJ |
| description | Abstract Lower respiratory tract infections caused by Streptococcus pneumoniae (Spn) are a leading cause of death globally. Here we investigate the bronchial epithelial cellular response to Spn infection on a transcriptomic, proteomic and metabolic level. We found the NAD+ salvage pathway to be dysregulated upon infection in a cell line model, primary human lung tissue and in vivo in rodents, leading to a reduced production of NAD+. Knockdown of NAD+ salvage enzymes (NAMPT, NMNAT1) increased bacterial replication. NAD+ treatment of Spn inhibited its growth while growth of other respiratory pathogens improved. Boosting NAD+ production increased NAD+ levels in immortalized and primary cells and decreased bacterial replication upon infection. NAD+ treatment of Spn dysregulated the bacterial metabolism and reduced intrabacterial ATP. Enhancing the bacterial ATP metabolism abolished the antibacterial effect of NAD+. Thus, we identified the NAD+ salvage pathway as an antibacterial pathway in Spn infections, predicting an antibacterial mechanism of NAD+. |
| first_indexed | 2024-03-10T17:34:05Z |
| format | Article |
| id | doaj.art-f53e17d7ffee4a8b866fd16db80c5bb8 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:34:05Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-f53e17d7ffee4a8b866fd16db80c5bb82023-11-20T09:56:26ZengNature PortfolioNature Communications2041-17232023-10-0114111610.1038/s41467-023-41372-wNAD+ metabolism is a key modulator of bacterial respiratory epithelial infectionsBjörn Klabunde0André Wesener1Wilhelm Bertrams2Isabell Beinborn3Nicole Paczia4Kristin Surmann5Sascha Blankenburg6Jochen Wilhelm7Javier Serrania8Kèvin Knoops9Eslam M. Elsayed10Katrin Laakmann11Anna Lena Jung12Andreas Kirschbaum13Sven Hammerschmidt14Belal Alshaar15Nicolas Gisch16Mobarak Abu Mraheil17Anke Becker18Uwe Völker19Evelyn Vollmeister20Birke J. Benedikter21Bernd Schmeck22Institute for Lung Research, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Philipps-Universität MarburgInstitute for Lung Research, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Philipps-Universität MarburgInstitute for Lung Research, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Philipps-Universität MarburgInstitute for Lung Research, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Philipps-Universität MarburgCore Facility for Metabolomics and Small Molecule Mass Spectrometry, Max Planck Institute for Terrestrial MicrobiologyDepartment of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine GreifswaldDepartment of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine GreifswaldInstitute for Lung Health (ILH)Center for Synthetic Microbiology (SYNMIKRO), Philipps-Universität MarburgMicroscopy CORE Lab, Maastricht Multimodal Molecular Imaging Institute (M4I), Maastricht UniversityCenter for Synthetic Microbiology (SYNMIKRO), Philipps-Universität MarburgInstitute for Lung Research, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Philipps-Universität MarburgInstitute for Lung Research, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Philipps-Universität MarburgDepartment of Visceral, Thoracic and Vascular Surgery, University Hospital Gießen and Marburg (UKGM)Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of GreifswaldDivision of Bioanalytical Chemistry, Priority Area Infections, Research Center Borstel, Leibniz Lung CenterDivision of Bioanalytical Chemistry, Priority Area Infections, Research Center Borstel, Leibniz Lung CenterInstitute for Medical Microbiology, Justus-Liebig Universität GiessenCenter for Synthetic Microbiology (SYNMIKRO), Philipps-Universität MarburgDepartment of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine GreifswaldInstitute for Lung Research, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Philipps-Universität MarburgInstitute for Lung Research, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Philipps-Universität MarburgInstitute for Lung Research, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Philipps-Universität MarburgAbstract Lower respiratory tract infections caused by Streptococcus pneumoniae (Spn) are a leading cause of death globally. Here we investigate the bronchial epithelial cellular response to Spn infection on a transcriptomic, proteomic and metabolic level. We found the NAD+ salvage pathway to be dysregulated upon infection in a cell line model, primary human lung tissue and in vivo in rodents, leading to a reduced production of NAD+. Knockdown of NAD+ salvage enzymes (NAMPT, NMNAT1) increased bacterial replication. NAD+ treatment of Spn inhibited its growth while growth of other respiratory pathogens improved. Boosting NAD+ production increased NAD+ levels in immortalized and primary cells and decreased bacterial replication upon infection. NAD+ treatment of Spn dysregulated the bacterial metabolism and reduced intrabacterial ATP. Enhancing the bacterial ATP metabolism abolished the antibacterial effect of NAD+. Thus, we identified the NAD+ salvage pathway as an antibacterial pathway in Spn infections, predicting an antibacterial mechanism of NAD+.https://doi.org/10.1038/s41467-023-41372-w |
| spellingShingle | Björn Klabunde André Wesener Wilhelm Bertrams Isabell Beinborn Nicole Paczia Kristin Surmann Sascha Blankenburg Jochen Wilhelm Javier Serrania Kèvin Knoops Eslam M. Elsayed Katrin Laakmann Anna Lena Jung Andreas Kirschbaum Sven Hammerschmidt Belal Alshaar Nicolas Gisch Mobarak Abu Mraheil Anke Becker Uwe Völker Evelyn Vollmeister Birke J. Benedikter Bernd Schmeck NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections Nature Communications |
| title | NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections |
| title_full | NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections |
| title_fullStr | NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections |
| title_full_unstemmed | NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections |
| title_short | NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections |
| title_sort | nad metabolism is a key modulator of bacterial respiratory epithelial infections |
| url | https://doi.org/10.1038/s41467-023-41372-w |
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