11 research outputs found
Consequences of concurrent Ascaridia galli and Escherichia coli infections in chickens
Three experiments were carried out to examine the consequences of concurrent infections with Ascaridia galli and Escherichia coli in chickens raised for table egg production. Characteristic pathological lesions including airsacculitis, peritonitis and/or polyserositis were seen in all groups infected with E. coli. Furthermore, a trend for increased mortality rates was observed in groups infected with both organisms which, however, could not be confirmed statistically. The mean worm burden was significantly lower in combined infection groups compared to groups infected only with A. galli. It was also shown that combined infections of E. coli and A. galli had an added significant negative impact on weight gain
Eeyarestatin 1 interferes with both retrograde and anterograde intracellular trafficking pathways
Background: The small molecule Eeyarestatin I (ESI) inhibits the endoplasmic reticulum (ER)-cytosol dislocation and
subsequent degradation of ERAD (ER associated protein degradation) substrates. Toxins such as ricin and Shiga/Shiga-like
toxins (SLTx) are endocytosed and trafficked to the ER. Their catalytic subunits are thought to utilise ERAD-like mechanisms
to dislocate from the ER into the cytosol, where a proportion uncouples from the ERAD process, recovers a catalytic
conformation and destroys their cellular targets. We therefore investigated ESI as a potential inhibitor of toxin dislocation.
Methodology and Principal Findings: Using cytotoxicity measurements, we found no role for ESI as an inhibitor of toxin
dislocation from the ER, but instead found that for SLTx, ESI treatment of cells was protective by reducing the rate of toxin
delivery to the ER. Microscopy of the trafficking of labelled SLTx and its B chain (lacking the toxic A chain) showed a delay in
its accumulation at a peri-nuclear location, confirmed to be the Golgi by examination of SLTx B chain metabolically labelled
in the trans-Golgi cisternae. The drug also reduced the rate of endosomal trafficking of diphtheria toxin, which enters the
cytosol from acidified endosomes, and delayed the Golgi-specific glycan modifications and eventual plasma membrane
appearance of tsO45 VSV-G protein, a classical marker for anterograde trafficking.
Conclusions and Significance: ESI acts on one or more components that function during vesicular transport, whilst at least
one retrograde trafficking pathway, that of ricin, remains unperturbed