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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 : Cellular microbiology

Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cellular microbiology - 20 May 2010

Rolando M, Stefani C, Flatau G, Auberger P, Mettouchi A, Mhlanga M, Rapp U, Galmiche A, Lemichez E

Link to Pubmed [PMID] – 20088950

Cell. Microbiol. 2010 Jul;12(7):891-905

We have investigated how Bacillus anthracis lethal toxin (LT) triggers caspase-3 activation and the formation of thick actin cables in human endothelial cells. By DNA array analysis we show that LT has a major impact on the cell transcriptome and we identify key host genes involved in LT cytotoxic effects. Indeed, upregulation of TRAIL and downregulation of XIAP both participate in LT-induced caspase-3 activation. LT induces a downregulation of the immediate early gene and master regulator of transcription egr1. Importantly, its re-expression in LT-intoxicated cells blocks caspase-3 activation. In parallel, we found that the formation of actin cables induced by LT occurs in the absence of direct activation of RhoA/ROCK signalling. We show that knock-down of cortactin and rhophilin-2 under conditions of calponin-1 expression defines the minimal set of genes regulated by LT for actin cable formation. Together our data establish that the modulation of the cell transcriptome by LT plays a key role in triggering human endothelial cell toxicity.

http://www.ncbi.nlm.nih.gov/pubmed/20088950