{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/176"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/176","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"Mechanism of action of AexU, a new type III secretion system effector from an emerging human pathogen Aeromonas hydrophila","abstract":"Our laboratory first reported the complete sequence of the type III secretion system (T3SS) from a diarrheal isolate SSU of A. hydrophila. We identified an effector protein (designated as AexU) of the T3SS, which exhibited ADP-ribosyltransferase (ADPRT) and GTPase-activating protein (GAP) activity. AexU was successfully expressed in the HeLa cell Tet-Off system and I provided evidence that cells expressing and producing the full length AexU showed actin reorganization followed by apoptosis. Earlier, we showed that the ÄaexU null mutant was attenuated in a mouse model, and I now demonstrated that while the parental A. hydrophila strain could be detected in the lung, liver, and spleen of infected mice, the ÄaexU mutant was rapidly cleared from these organs resulting in increased survivability of animals. The GAP activity of AexU was mainly responsible for host cell apoptosis and disruption of actin filaments. Further, AexU prevented phosphorylation of c-Jun, JNK and IêBá and inhibited IL-6 and IL-8 secretion from HeLa cells. Our data indicated that AexU operated by inhibiting NF-êB and inactivating Rho GTPases. Importantly, however, when the ÄaexU null mutant was complemented with the mutated aexU gene devoid of ADPRT and GAP activities, a higher mortality rate in mice with concomitant increase in the production of proinflammatory cytokines/chemokines was noted. These data indicated that either such a mutated AexU is a potent inducer of them or that AexU possesses yet another unknown activity that is modulated by ADPRT and GAP activities and results in this aberrant cytokine/chemokine production responsible for increased animal death.","abstract_html":"Our laboratory first reported the complete sequence of the type III secretion system (T3SS) from a diarrheal isolate SSU of A. hydrophila. We identified an effector protein (designated as AexU) of the T3SS, which exhibited ADP-ribosyltransferase (ADPRT) and GTPase-activating protein (GAP) activity. AexU was successfully expressed in the HeLa cell Tet-Off system and I provided evidence that cells expressing and producing the full length AexU showed actin reorganization followed by apoptosis. Earlier, we showed that the ÄaexU null mutant was attenuated in a mouse model, and I now demonstrated that while the parental A. hydrophila strain could be detected in the lung, liver, and spleen of infected mice, the ÄaexU mutant was rapidly cleared from these organs resulting in increased survivability of animals. The GAP activity of AexU was mainly responsible for host cell apoptosis and disruption of actin filaments. Further, AexU prevented phosphorylation of c-Jun, JNK and IêBá and inhibited IL-6 and IL-8 secretion from HeLa cells. Our data indicated that AexU operated by inhibiting NF-êB and inactivating Rho GTPases. Importantly, however, when the ÄaexU null mutant was complemented with the mutated aexU gene devoid of ADPRT and GAP activities, a higher mortality rate in mice with concomitant increase in the production of proinflammatory cytokines/chemokines was noted. These data indicated that either such a mutated AexU is a potent inducer of them or that AexU possesses yet another unknown activity that is modulated by ADPRT and GAP activities and results in this aberrant cytokine/chemokine production responsible for increased animal death.","abstract_has_math":false,"creators":["Johanna Carolina Sierra"],"institution":"The University of Texas Medical Branch","degree_name":"PhD","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Ashok Chopra"],"committee_chairs":[],"committee_members":["Vladimir Motin","Judith Johnson","Johnny Peterson","Eric Smith"],"year":2010,"date_issued":"2010-07-08","date_published":"2010-07-08","updated_at":"2026-07-24T05:50:59Z","subjects":["type III secretion system","septicemic mouse model of infection","GAP activity","AexU","Aeromonas hydrophila","ADP-ribosyltransferase activity"],"languages":["eng"],"rights":["Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-07202010-135030"],"render_values":[{"text":"etd-07202010-135030","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2152.3/176","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Ashok Chopra"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Vladimir Motin","Judith Johnson","Johnny Peterson","Eric Smith"]},{"key":"dc:creator","label":"Author","values":["Johanna Carolina Sierra"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2011-12-20T16:05:01Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2010-09-28","2011-12-20T16:05:01Z"]},{"key":"dc:date.issued","label":"Date","values":["2010-07-08"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["PhD"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["type III secretion system","septicemic mouse model of infection","GAP activity","AexU","Aeromonas hydrophila","ADP-ribosyltransferase activity"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-07202010-135030"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2152.3/176"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Our laboratory first reported the complete sequence of the type III secretion system (T3SS) from a diarrheal isolate SSU of A. hydrophila. We identified an effector protein (designated as AexU) of the T3SS, which exhibited ADP-ribosyltransferase (ADPRT) and GTPase-activating protein (GAP) activity. AexU was successfully expressed in the HeLa cell Tet-Off system and I provided evidence that cells expressing and producing the full length AexU showed actin reorganization followed by apoptosis. Earlier, we showed that the ÄaexU null mutant was attenuated in a mouse model, and I now demonstrated that while the parental A. hydrophila strain could be detected in the lung, liver, and spleen of infected mice, the ÄaexU mutant was rapidly cleared from these organs resulting in increased survivability of animals. The GAP activity of AexU was mainly responsible for host cell apoptosis and disruption of actin filaments. Further, AexU prevented phosphorylation of c-Jun, JNK and IêBá and inhibited IL-6 and IL-8 secretion from HeLa cells. Our data indicated that AexU operated by inhibiting NF-êB and inactivating Rho GTPases. Importantly, however, when the ÄaexU null mutant was complemented with the mutated aexU gene devoid of ADPRT and GAP activities, a higher mortality rate in mice with concomitant increase in the production of proinflammatory cytokines/chemokines was noted. These data indicated that either such a mutated AexU is a potent inducer of them or that AexU possesses yet another unknown activity that is modulated by ADPRT and GAP activities and results in this aberrant cytokine/chemokine production responsible for increased animal death."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["electronic"]},{"key":"dc:title","label":"Title","values":["Mechanism of action of AexU, a new type III secretion system effector from an emerging human pathogen Aeromonas hydrophila"]}]}],"canonical_facts":{"dc:contributor.advisor":["Ashok Chopra"],"dc:contributor.committeemember":["Vladimir Motin","Judith Johnson","Johnny Peterson","Eric Smith"],"dc:creator":["Johanna Carolina Sierra"],"dc:date.accessioned":["2011-12-20T16:05:01Z"],"dc:date.available":["2010-09-28","2011-12-20T16:05:01Z"],"dc:date.issued":["2010-07-08"],"dc:description.abstract":["Our laboratory first reported the complete sequence of the type III secretion system (T3SS) from a diarrheal isolate SSU of A. hydrophila. We identified an effector protein (designated as AexU) of the T3SS, which exhibited ADP-ribosyltransferase (ADPRT) and GTPase-activating protein (GAP) activity. AexU was successfully expressed in the HeLa cell Tet-Off system and I provided evidence that cells expressing and producing the full length AexU showed actin reorganization followed by apoptosis. Earlier, we showed that the ÄaexU null mutant was attenuated in a mouse model, and I now demonstrated that while the parental A. hydrophila strain could be detected in the lung, liver, and spleen of infected mice, the ÄaexU mutant was rapidly cleared from these organs resulting in increased survivability of animals. The GAP activity of AexU was mainly responsible for host cell apoptosis and disruption of actin filaments. Further, AexU prevented phosphorylation of c-Jun, JNK and IêBá and inhibited IL-6 and IL-8 secretion from HeLa cells. Our data indicated that AexU operated by inhibiting NF-êB and inactivating Rho GTPases. Importantly, however, when the ÄaexU null mutant was complemented with the mutated aexU gene devoid of ADPRT and GAP activities, a higher mortality rate in mice with concomitant increase in the production of proinflammatory cytokines/chemokines was noted. These data indicated that either such a mutated AexU is a potent inducer of them or that AexU possesses yet another unknown activity that is modulated by ADPRT and GAP activities and results in this aberrant cytokine/chemokine production responsible for increased animal death."],"dc:format.medium":["electronic"],"dc:identifier.other":["etd-07202010-135030"],"dc:identifier.uri":["http://hdl.handle.net/2152.3/176"],"dc:language.iso":["eng"],"dc:rights":["Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works."],"dc:subject":["type III secretion system","septicemic mouse model of infection","GAP activity","AexU","Aeromonas hydrophila","ADP-ribosyltransferase activity"],"dc:title":["Mechanism of action of AexU, a new type III secretion system effector from an emerging human pathogen Aeromonas hydrophila"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["PhD"],"thesis:institution_name":["The University of Texas Medical Branch"]},"updated_at":"2026-07-24T05:50:59Z"}