Unraveling the mechanism of action of a new type III secretion system effector AexU from Aeromonas hydrophila

Johanna C. Sierra, Giovanni Suarez, Jian Sha, Wallace B. Baze, Sheri M. Foltz, Ashok K. Chopra

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

We recently characterized a T3SS effector, AexU, from a diarrheal isolate SSU of Aeromonas hydrophila, which exhibited ADP-ribosyltransferase (ADPRT) activity. Here we provided evidence that AexU also possessed GTPase-activating protein (GAP) activity, which was mainly responsible for host cell apoptosis and disruption of actin filaments. Earlier, we showed that the Δ aexU null mutant was attenuated in a mouse model, and we now demonstrated that while the parental A. hydrophila strain could be detected in the lung, liver, and spleen of infected mice, the Δ aexU mutant was rapidly cleared from these organs resulting in increased survivability of animals. Further, AexU prevented phosphorylation of c-Jun, JNK and IκBα and inhibited IL-6 and IL-8 secretion from HeLa cells. Our data indicated that AexU operated by inhibiting NF-κB and inactivating Rho GTPases. Importantly, however, when the Δ aexU 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 pro-inflammatory 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.

Original languageEnglish (US)
Pages (from-to)122-134
Number of pages13
JournalMicrobial Pathogenesis
Volume49
Issue number3
DOIs
StatePublished - Sep 2010

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Keywords

  • ADP-ribosyltransferase activity
  • Aeromonas hydrophila
  • AexU
  • Apoptosis
  • GAP activity
  • HeLa Tet-Off cells
  • Septicemic mouse model of infection
  • Site-directed mutagenesis
  • T3SS

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

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