Mechanism of action of AexU, a new type III secretion system effector from an emerging human pathogen Aeromonas hydrophila

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dc.contributor.advisorAshok Chopraen_US
dc.contributor.committeeMemberVladimir Motinen_US
dc.contributor.committeeMemberJudith Johnsonen_US
dc.contributor.committeeMemberJohnny Petersonen_US
dc.contributor.committeeMemberEric Smithen_US
dc.creatorJohanna Carolina Sierraen_US
dc.date.accessioned2011-12-20T16:05:01Z
dc.date.available2010-09-28en_US
dc.date.available2011-12-20T16:05:01Z
dc.date.created2010-07-20en_US
dc.date.issued2010-07-08en_US
dc.description.abstractOur 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.en_US
dc.format.mediumelectronicen_US
dc.identifier.otheretd-07202010-135030en_US
dc.identifier.urihttp://hdl.handle.net/2152.3/176
dc.language.isoengen_US
dc.rightsCopyright © 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.en_US
dc.subjecttype III secretion systemen_US
dc.subjectsepticemic mouse model of infectionen_US
dc.subjectGAP activityen_US
dc.subjectAexUen_US
dc.subjectAeromonas hydrophilaen_US
dc.subjectADP-ribosyltransferase activityen_US
dc.titleMechanism of action of AexU, a new type III secretion system effector from an emerging human pathogen Aeromonas hydrophilaen_US
dc.type.genredissertationen_US
dc.type.materialtexten_US
thesis.degree.departmentMicrobiology and Immunologyen_US
thesis.degree.grantorThe University of Texas Medical Branchen_US
thesis.degree.levelDoctoralen_US
thesis.degree.namePhDen_US

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