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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity
Cellular Microbiology, Volume 12, No. 7, Year 2010
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Description
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. © 2010 Blackwell Publishing Ltd.
Authors & Co-Authors
Rolando, Monica
France, Nice
Centre Méditerranéen de Médecine Moléculaire
France, Nice
Toxines Microbiennes Dans la Relation Hôte Pathogènes
France, Nice
Université Côte D'azur
Stefani, Caroline
France, Nice
Centre Méditerranéen de Médecine Moléculaire
France, Nice
Toxines Microbiennes Dans la Relation Hôte Pathogènes
France, Nice
Université Côte D'azur
Flatau, Gilles N.
France, Nice
Centre Méditerranéen de Médecine Moléculaire
France, Nice
Toxines Microbiennes Dans la Relation Hôte Pathogènes
France, Nice
Université Côte D'azur
Auberger, Patrick
France, Nice
Centre Méditerranéen de Médecine Moléculaire
France, Nice
Université Côte D'azur
France, Nice
Mort Cellulaire Différentiation et Cancer
Mettouchi, Amel
France, Nice
Mort Cellulaire Différentiation et Cancer
France, Paris
Inserm
Mhlanga, Musa M.
South Africa, Pretoria
Gene Expression and Biophysics Group
Rapp, Ulf
France, Nice
Centre Méditerranéen de Médecine Moléculaire
Germany, Wurzburg
Medizinische Fakultät
Galmiche, Antoine
Germany, Wurzburg
Medizinische Fakultät
Lemichez, Emmanuel
France, Nice
Centre Méditerranéen de Médecine Moléculaire
France, Nice
Toxines Microbiennes Dans la Relation Hôte Pathogènes
France, Nice
Université Côte D'azur
France, Nice
Centre Hospitalier Universitaire de Nice, Hôpital L'archet
Statistics
Citations: 32
Authors: 9
Affiliations: 8
Identifiers
Doi:
10.1111/j.1462-5822.2010.01438.x
ISSN:
14625814
e-ISSN:
14625822
Research Areas
Genetics And Genomics