Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence

BMC Genomics

Research Article

Andreas Schlüter¹  Tobias Müller²  Chunguang Liang²  Thomas Dandekar²  Marcus Dittrich³  Jochen Blom⁴  Alexander Goesmann⁴  Biju Joseph Ampattu⁵  Christoph Schoen⁵  Laura Hagmann⁵  Elizaveta Krol⁶  Anke Becker⁶ 

[1] Center for Biotechnology (CeBiTec), Bielefeld University, Universitätsstr. 27, 33615, Bielefeld, Germany;Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074, Würzburg, Germany;Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074, Würzburg, Germany;Department of Human Genetics, Biocenter, University of Würzburg, Am Hubland, 97074, Würzburg, Germany;Institute for Bioinformatics and Systems Biology, Justus Liebig University Gießen, Heinrich-Buff-Ring 58, 35392, Gießen, Germany;Institute for Hygiene and Microbiology, Joseph-Schneider-Straße 2, University of Würzburg, 97080, Würzburg, Germany;LOEWE-Center for Synthetic Microbiology, Hans-Meerwein-Straße, 35032, Marburg, Germany;

关键词: Neisseria meningitidis;    Virulence;    Regulatory evolution;    Systems biology;    Metabolism;    Cryptic genetic variation;    Stringent response;    MITE;    RelA;   

DOI  :  10.1186/s12864-017-3616-7

 received in 2016-08-24, accepted in 2017-03-10,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundCommensal 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.ResultsDespite 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© The Author(s). 2017