Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence
Abstract Background Commensal bacteria like Neisseria meningitidis sometimes cause serious disease. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous hints towards indispensable virulence factors. Here, in a systems biological approach we compared gene...
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BMC
2017-04-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-017-3616-7 |
| _version_ | 1828279222975594496 |
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| author | Biju Joseph Ampattu Laura Hagmann Chunguang Liang Marcus Dittrich Andreas Schlüter Jochen Blom Elizaveta Krol Alexander Goesmann Anke Becker Thomas Dandekar Tobias Müller Christoph Schoen |
| author_facet | Biju Joseph Ampattu Laura Hagmann Chunguang Liang Marcus Dittrich Andreas Schlüter Jochen Blom Elizaveta Krol Alexander Goesmann Anke Becker Thomas Dandekar Tobias Müller Christoph Schoen |
| author_sort | Biju Joseph Ampattu |
| collection | DOAJ |
| description | Abstract Background Commensal bacteria like Neisseria meningitidis sometimes cause serious disease. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous hints towards indispensable virulence factors. Here, in a systems biological approach we compared gene expression of the invasive strain MC58 and the carriage strain α522 under different ex vivo conditions mimicking commensal and virulence compartments to assess the strain-specific impact of gene regulation on meningococcal virulence. Results Despite indistinguishable ex vivo phenotypes, both strains differed in the expression of over 500 genes under infection mimicking conditions. These differences comprised in particular metabolic and information processing genes as well as genes known to be involved in host-damage such as the nitrite reductase and numerous LOS biosynthesis genes. A model based analysis of the transcriptomic differences in human blood suggested ensuing metabolic flux differences in energy, glutamine and cysteine metabolic pathways along with differences in the activation of the stringent response in both strains. In support of the computational findings, experimental analyses revealed differences in cysteine and glutamine auxotrophy in both strains as well as a strain and condition dependent essentiality of the (p)ppGpp synthetase gene relA and of a short non-coding AT-rich repeat element in its promoter region. Conclusions Our data suggest that meningococcal virulence is linked to transcriptional buffering of cryptic genetic variation in metabolic genes including global stress responses. They further highlight the role of regulatory elements for bacterial virulence and the limitations of model strain approaches when studying such genetically diverse species as N. meningitidis. |
| first_indexed | 2024-04-13T07:40:40Z |
| format | Article |
| id | doaj.art-cb99958ad15d4bc1b2e4d921c6e5433f |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-13T07:40:40Z |
| publishDate | 2017-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-cb99958ad15d4bc1b2e4d921c6e5433f2022-12-22T02:55:54ZengBMCBMC Genomics1471-21642017-04-0118113610.1186/s12864-017-3616-7Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulenceBiju Joseph Ampattu0Laura Hagmann1Chunguang Liang2Marcus Dittrich3Andreas Schlüter4Jochen Blom5Elizaveta Krol6Alexander Goesmann7Anke Becker8Thomas Dandekar9Tobias Müller10Christoph Schoen11Institute for Hygiene and Microbiology, Joseph-Schneider-Straße 2, University of WürzburgInstitute for Hygiene and Microbiology, Joseph-Schneider-Straße 2, University of WürzburgDepartment of Bioinformatics, Biocenter, University of WürzburgDepartment of Bioinformatics, Biocenter, University of WürzburgCenter for Biotechnology (CeBiTec), Bielefeld UniversityInstitute for Bioinformatics and Systems Biology, Justus Liebig University GießenLOEWE-Center for Synthetic MicrobiologyInstitute for Bioinformatics and Systems Biology, Justus Liebig University GießenLOEWE-Center for Synthetic MicrobiologyDepartment of Bioinformatics, Biocenter, University of WürzburgDepartment of Bioinformatics, Biocenter, University of WürzburgInstitute for Hygiene and Microbiology, Joseph-Schneider-Straße 2, University of WürzburgAbstract Background Commensal bacteria like Neisseria meningitidis sometimes cause serious disease. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous hints towards indispensable virulence factors. Here, in a systems biological approach we compared gene expression of the invasive strain MC58 and the carriage strain α522 under different ex vivo conditions mimicking commensal and virulence compartments to assess the strain-specific impact of gene regulation on meningococcal virulence. Results Despite indistinguishable ex vivo phenotypes, both strains differed in the expression of over 500 genes under infection mimicking conditions. These differences comprised in particular metabolic and information processing genes as well as genes known to be involved in host-damage such as the nitrite reductase and numerous LOS biosynthesis genes. A model based analysis of the transcriptomic differences in human blood suggested ensuing metabolic flux differences in energy, glutamine and cysteine metabolic pathways along with differences in the activation of the stringent response in both strains. In support of the computational findings, experimental analyses revealed differences in cysteine and glutamine auxotrophy in both strains as well as a strain and condition dependent essentiality of the (p)ppGpp synthetase gene relA and of a short non-coding AT-rich repeat element in its promoter region. Conclusions Our data suggest that meningococcal virulence is linked to transcriptional buffering of cryptic genetic variation in metabolic genes including global stress responses. They further highlight the role of regulatory elements for bacterial virulence and the limitations of model strain approaches when studying such genetically diverse species as N. meningitidis.http://link.springer.com/article/10.1186/s12864-017-3616-7Neisseria meningitidisVirulenceRegulatory evolutionSystems biologyMetabolismCryptic genetic variation |
| spellingShingle | Biju Joseph Ampattu Laura Hagmann Chunguang Liang Marcus Dittrich Andreas Schlüter Jochen Blom Elizaveta Krol Alexander Goesmann Anke Becker Thomas Dandekar Tobias Müller Christoph Schoen Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence BMC Genomics Neisseria meningitidis Virulence Regulatory evolution Systems biology Metabolism Cryptic genetic variation |
| title | Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence |
| title_full | Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence |
| title_fullStr | Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence |
| title_full_unstemmed | Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence |
| title_short | Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence |
| title_sort | transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence |
| topic | Neisseria meningitidis Virulence Regulatory evolution Systems biology Metabolism Cryptic genetic variation |
| url | http://link.springer.com/article/10.1186/s12864-017-3616-7 |
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