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Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence

Please always quote using this URN: urn:nbn:de:bvb:20-opus-157534
  • 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: DespiteBackground: 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.show moreshow less

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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 SchoenORCiD
URN:urn:nbn:de:bvb:20-opus-157534
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Hygiene und Mikrobiologie
Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):BMC Genomics
Year of Completion:2017
Volume:18
Issue:282
Source:BMC Genomics (2017) 18:282. DOI: 10.1186/s12864-017-3616-7
DOI:https://doi.org/10.1186/s12864-017-3616-7
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:MITE; cryptic; genetic variation; metabolism; neisseria meningitidis; relA; stringent response; systems biology; virulenceregulatory evolution
Release Date:2018/02/19
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2017
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International