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

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Title: Mechanism of action of AexU, a new type III secretion system effector from an emerging human pathogen Aeromonas hydrophila
Author: Johanna Carolina Sierra
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 .
URI: http : / /hdl .handle .net /2152 .3 /176
Date: 2010-07-08

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Mechanism of action of AexU, a new type III secretion system effector from an emerging human pathogen Aeromonas hydrophila. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /176 .

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