The Pseudomonas aeruginosa type III secreted toxin ExoT is necessary and sufficient to induce apoptosis in epithelial cells.
Type III secreted (T3SS) effectors are important virulence factors in acute infections caused by Pseudomonas aeruginosa. PA103, a well-studied human lung isolate, encodes and secretes two effectors, ExoU and ExoT. ExoU is a potent cytotoxin that causes necrotic cell death. In addition, PA103 can induce cell death in macrophages in an ExoU-independent but T3SS-dependent manner. We now demonstrate that ExoT is both necessary and sufficient to cause apoptosis in HeLa cells and that it activates the mitochondrial/cytochrome c-dependent apoptotic pathway. We further show that ExoT induction of cell death is primarily dependent on its ADP ribosyltransferase domain activity. Our data also indicate that the T3SS apparatus can cause necrotic cell death, which is effectively blocked by ExoT, suggesting that P. aeruginosa may have evolved strategies to prevent T3SS-induced necrosis.
Shafikhani
Sasha H
SH
Department of Medicine, University of California, San Francisco, CA 94143, USA.
Morales
Christina
C
Engel
Joanne
J
D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000254:growth & development / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D001426:Bacterial Proteins; C477521:ExoT protein, Pseudomonas aeruginosa; D020690:GTPase-Activating Proteins; D011993:Recombinant Fusion Proteins; C111749:pseudomonas exoprotein A protein, Pseudomonas aeruginosa; D049452:Green Fluorescent Proteins; D045304:Cytochromes c; D036002:ADP Ribose Transferases