Open AccessTranscriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity
Author(s) -
Rolando Monica,
Stefani Caroline,
Flatau Gilles,
Auberger Patrick,
Mettouchi Amel,
Mhlanga Musa,
Rapp Ulf,
Galmiche Antoine,
Lemichez Emmanuel
Publication year - 2010
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2010.01438.x
Subject(s) - downregulation and upregulation , biology , transcriptome , microbiology and biotechnology , cortactin , gene expression , cell , gene , cytoskeleton , genetics
Summary 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.