Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence

Ampattu BJ, Hagmann L, Liang C, Dittrich M, Schlüter A, Blom J, Krol E, Goesmann A, Becker A, Dandekar T, Mueller T, et al. (2017)
BMC Genomics 18: 282.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
Download
Es wurde kein Volltext hochgeladen. Nur Publikationsnachweis!
Autor/in
; ; ; ; ; ; ; ; ; ; ;
Alle
Abstract / Bemerkung
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 alpha 522 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.
Stichworte
Neisseria meningitidis; Virulence; Regulatory evolution; Systems; biology; Metabolism; Cryptic genetic variation; Stringent response; MITE; RelA
Erscheinungsjahr
2017
Zeitschriftentitel
BMC Genomics
Band
18
Art.-Nr.
282
eISSN
1471-2164
Page URI
https://pub.uni-bielefeld.de/record/2911007

Zitieren

Ampattu BJ, Hagmann L, Liang C, et al. Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence. BMC Genomics. 2017;18: 282.
Ampattu, B. J., Hagmann, L., Liang, C., Dittrich, M., Schlüter, A., Blom, J., Krol, E., et al. (2017). Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence. BMC Genomics, 18, 282. doi:10.1186/s12864-017-3616-7
Ampattu, B. J., Hagmann, L., Liang, C., Dittrich, M., Schlüter, A., Blom, J., Krol, E., Goesmann, A., Becker, A., Dandekar, T., et al. (2017). Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence. BMC Genomics 18:282.
Ampattu, B.J., et al., 2017. Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence. BMC Genomics, 18: 282.
B.J. Ampattu, et al., “Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence”, BMC Genomics, vol. 18, 2017, : 282.
Ampattu, B.J., Hagmann, L., Liang, C., Dittrich, M., Schlüter, A., Blom, J., Krol, E., Goesmann, A., Becker, A., Dandekar, T., Mueller, T., Schoen, C.: Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence. BMC Genomics. 18, : 282 (2017).
Ampattu, Biju Joseph, Hagmann, Laura, Liang, Chunguang, Dittrich, Marcus, Schlüter, Andreas, Blom, Jochen, Krol, Elizaveta, Goesmann, Alexander, Becker, Anke, Dandekar, Thomas, Mueller, Tobias, and Schoen, Christoph. “Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence”. BMC Genomics 18 (2017): 282.

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 28388876
PubMed | Europe PMC

Suchen in

Google Scholar