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 Chopra

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 - 2010

Fingerprint

ADP Ribose Transferases
Aeromonas hydrophila
GTPase-Activating Proteins
Chemokines
Cytokines
rho GTP-Binding Proteins
Interleukin-8
Actin Cytoskeleton
HeLa Cells
Interleukin-6
Spleen
Phosphorylation
Apoptosis
Lung
Mortality
Liver
Genes
Type III Secretion Systems

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
  • Medicine(all)

Cite this

Unraveling the mechanism of action of a new type III secretion system effector AexU from Aeromonas hydrophila. / Sierra, Johanna C.; Suarez, Giovanni; Sha, Jian; Baze, Wallace B.; Foltz, Sheri M.; Chopra, Ashok.

In: Microbial Pathogenesis, Vol. 49, No. 3, 2010, p. 122-134.

Research output: Contribution to journalArticle

Sierra, Johanna C. ; Suarez, Giovanni ; Sha, Jian ; Baze, Wallace B. ; Foltz, Sheri M. ; Chopra, Ashok. / Unraveling the mechanism of action of a new type III secretion system effector AexU from Aeromonas hydrophila. In: Microbial Pathogenesis. 2010 ; Vol. 49, No. 3. pp. 122-134.
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