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ExoS and ExoT are two homologous bifunctional Type III Secretion System (T3SS) virulence factors that induce apoptosis in target host cells. They possess a GTPase Activating Protein (GAP) domain at their N-termini, which share ~76% homology, and an ADP-ribosyltransferase (ADPRT) domain at their C-termini, which target non-overlapping substrates. Both the GAP and the ADPRT domains contribute to ExoT\u2019s cytotoxicity in target epithelial cells, whereas, ExoS-induced apoptosis is reported to be primarily due to its ADPRT domain. In this report, we demonstrate that ExoS\/GAP domain is both necessary and sufficient to induce mitochondrial apoptosis. Our data demonstrate that intoxication with ExoS\/GAP domain leads to enrichment of Bax and Bim into the mitochondrial outer-membrane, disruption of mitochondrial membrane and release of and cytochrome\n                    <jats:italic>c<\/jats:italic>\n                    into the cytosol, which activates initiator caspase-9 and effector caspase-3, that executes cellular death. We posit that the contribution of the GAP domain in ExoS-induced apoptosis was overlooked in prior studies due to its slower kinetics of cytotoxicity as compared to ADPRT. Our data clarify the field and reveal a novel virulence function for ExoS\/GAP as an inducer of apoptosis.\n                  <\/jats:p>","DOI":"10.1038\/s41598-018-32491-2","type":"journal-article","created":{"date-parts":[[2018,9,13]],"date-time":"2018-09-13T05:47:42Z","timestamp":1536817662000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Pseudomonas aeruginosa ExoS Induces Intrinsic Apoptosis in Target Host Cells in a Manner That is Dependent on its GAP Domain Activity"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4181-2972","authenticated-orcid":false,"given":"Amber","family":"Kaminski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kajal H.","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef W.","family":"Goldufsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha Won","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6987-2550","authenticated-orcid":false,"given":"Vineet","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1755-9997","authenticated-orcid":false,"given":"Sasha H.","family":"Shafikhani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,9,19]]},"reference":[{"key":"32491_CR1","doi-asserted-by":"crossref","unstructured":"Engel, J. 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