Ir. Henderson et al., Involvement of the enteroaggregative Escherichia coli plasmid-encoded toxin in causing human intestinal damage, INFEC IMMUN, 67(10), 1999, pp. 5338-5344
Enteroaggregative Escherichia coli (EAEC) strains have been shown to adhere
to human intestinal tissue in an in vitro organ culture (IVOC) model, and
certain strains manifest mucosal toxicity We have recently described the EA
EC plasmid-encoded toxin (Pet), a member of a specific serine protease subc
lass of the autotransporter proteins. When injected into rat ileal loops, P
et both elicited fluid accumulation and had cytotoxic effects on the mucosa
. Furthermore, the Pet protein caused rises in short circuit current from m
t jejunal tissue mounted in a Ussing chamber and rounding of intestinal epi
thelial cells in culture. We therefore hypothesized that the mucosal pathol
ogy induced by EAEC strains in the IVOC model was related to expression of
the Pet protein. Here, we have examined the effects of EAEC strain 042 and
its isogenic pet mutant in the IVOC model. 042-infected colonic explants ex
hibited dilation of crypt openings, increased cell rounding, development of
prominent intercrypt crevices, and absence of epical mucus plugs. Colonic
tissue incubated with the pet mutant exhibited significantly fewer mucosal
abnormalities both subjectively and as quantitated morphometrically by meas
urement of crypt aperture diameter. Mucosal effects were restored upon comp
lementation of the pet mutation in trans. Interestingly, we found that the
ability of 042 to damage T84 cells was not dependent upon Pet. The data sug
gest that the Pet toxin is active on the human intestinal mucose but that E
AEC may have other mechanisms of eliciting mucosal damage.