Differences in Virulence Gene Expression Between Human Blood and Stool Clade 1 ST828CC Isolates

Background: colonise the gastrointestinal tract of warm-blooded animals and are major enteropathogens in humans. is less common than and accounts for about 10% of the total number of infections although the two species seem to share many virulence determinants. bacteraemia is rare, estimated to occur in less than 1% of the infections, and the exact mechanisms regulating the progression of the infection from the gastrointestinal tract to the blood stream are unclear. Here, we looked at the contribution of to infections and further compared various virulence traits in clade 1 blood and stool isolates.

Results: We assessed the numbers of and among typed isolates in the PubMLST database and found that accounted for 25.9% of blood isolates, but only 8.9% of the stool isolates. Phylogenetic analysis of 128 clade 1 whole genome sequences deposited to NCBI revealed no specific clustering of the human blood, stool or animal isolates. Of the six isolates chosen for phenotypic analyses, stool isolates adhered significantly better to human HT-29 colon cancer cells than the blood isolates, while there was no difference in induced IL-8 levels between the isolates. Furthermore, the stool isolates had two- to fourfold higher RNA expression levels of the , and virulence genes than the blood isolates. Finally, we looked at the gene structure of the and toxin genes and found numerous nucleotide additions and deletions disrupting the open reading frames. In contrast to 58% isolates of animal origin, only 38% and 32% of human blood and stool isolates, respectively, had all three genes intact, a prerequisite to produce functional toxins.

Conclusions: This study reveals interesting differences between clade 1 isolates of human and animal origin on one hand, and also between human blood and stool isolates, on the other. The results suggest that might downregulate and/or inactivate various virulence determinants as the isolates pass from the animal host to the human gastrointestinal tract and enter the human blood stream.