Induction of transient macroapertures in endothelial cells through RhoA inhibition by Staphylococcus aureus factors.
The GTPase RhoA is a major regulator of the assembly of actin stress fibers and the contractility of the actomyosin cytoskeleton. The epidermal cell differentiation inhibitor (EDIN) and EDIN-like ADP-ribosyltransferases of Staphylococcus aureus catalyze the inactivation of RhoA, producing actin cable disruption. We report that purified recombinant EDIN and EDIN-producing S. aureus provoke large transcellular tunnels in endothelial cells that we have named macroapertures (MAs). These structures open transiently, followed by the appearance of actin-containing membrane waves extending over the aperture. Disruption of actin cables, either directly or indirectly, through rhoA RNAi knockdown also triggers the formation of MAs. Intoxication of endothelial monolayers by EDIN produces a loss of barrier function and provides direct access of the endothelium basement membrane to S. aureus.
Boyer
Laurent
L
Toxines Bactériennes dans la Relation Hôte-Pathogènes, U627, Faculté de Médecine, Institut National de la Santé et de la Recherche Médicale, INSERM, 06107 Nice Cedex 2, France.
Doye
Anne
A
Rolando
Monica
M
Flatau
Gilles
G
Munro
Patrick
P
Gounon
Pierre
P
Clément
René
R
Pulcini
Céline
C
Popoff
Michel R
MR
Mettouchi
Amel
A
Landraud
Luce
L
Dussurget
Olivier
O
Lemichez
Emmanuel
E
D036002:ADP Ribose Transferases / Q000302:isolation & purification / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D006801:Humans; D008969:Molecular Sequence Data; D034622:RNA Interference / Q000502:physiology; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000737:chemistry / Q000201:enzymology; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D011994:Recombinant Proteins; C067120:epidermal cell differentiation inhibitor, Staphylococcus aureus; D036002:ADP Ribose Transferases; D020742:rhoA GTP-Binding Protein