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© Carmen Buchrieser, Marie-Christine Prevost
Legionella pneumophila et son flagelle, bactérie responsable de pneumopathie aigue grave. Bactérie de l'environnement , l'émergence récente de cette maladie s'explique par son affinité pour les systèmes modernes d'alimentation en eau comme les tours de refroidissement. Image colorisée.
Publication : PLoS genetics

The Legionella pneumophila genome evolved to accommodate multiple regulatory mechanisms controlled by the CsrA-system.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in PLoS genetics - 01 Feb 2017

Sahr T, Rusniok C, Impens F, Oliva G, Sismeiro O, Coppée JY, Buchrieser C,

Link to Pubmed [PMID] – 28212376

Link to DOI – 10.1371/journal.pgen.1006629

PLoS Genet 2017 02; 13(2): e1006629

The carbon storage regulator protein CsrA regulates cellular processes post-transcriptionally by binding to target-RNAs altering translation efficiency and/or their stability. Here we identified and analyzed the direct targets of CsrA in the human pathogen Legionella pneumophila. Genome wide transcriptome, proteome and RNA co-immunoprecipitation followed by deep sequencing of a wild type and a csrA mutant strain identified 479 RNAs with potential CsrA interaction sites located in the untranslated and/or coding regions of mRNAs or of known non-coding sRNAs. Further analyses revealed that CsrA exhibits a dual regulatory role in virulence as it affects the expression of the regulators FleQ, LqsR, LetE and RpoS but it also directly regulates the timely expression of over 40 Dot/Icm substrates. CsrA controls its own expression and the stringent response through a regulatory feedback loop as evidenced by its binding to RelA-mRNA and links it to quorum sensing and motility. CsrA is a central player in the carbon, amino acid, fatty acid metabolism and energy transfer and directly affects the biosynthesis of cofactors, vitamins and secondary metabolites. We describe the first L. pneumophila riboswitch, a thiamine pyrophosphate riboswitch whose regulatory impact is fine-tuned by CsrA, and identified a unique regulatory mode of CsrA, the active stabilization of RNA anti-terminator conformations inside a coding sequence preventing Rho-dependent termination of the gap operon through transcriptional polarity effects. This allows L. pneumophila to regulate the pentose phosphate pathway and the glycolysis combined or individually although they share genes in a single operon. Thus the L. pneumophila genome has evolved to acclimate at least five different modes of regulation by CsrA giving it a truly unique position in its life cycle.