Dynamic Gene Network Analysis of Caco-2 Cell Response to Shiga Toxin-Producing Escherichia coli-Associated Hemolytic–Uremic Syndrome

A dynamic network approach was conducted to investigate the differential Caco-2 response to two STEC isolates - EH41, isolated from a HUS patient in Australia, and Ec472/01, isolated from bovine feces in Brazil - along in vitro enterocyte-bacteria interaction. The genomic analysis was based on temporal gene co-expression analysis (GCN) data in order to gain a better understanding on the molecular mechanisms underlying the capacity to cause HUS. The GCN topological analyses for Caco-2/EH41 group revealed loss of the scale-free status after one hour of interaction, persistence of this condition along the second hour and establishment of a new gene hierarchy thereafter. These events resemble the gene network mechanism of health-disease transition. The new established network represents an adaptive cell response to the pathogen and not the return to a “normal” state. Conversely, the networks for Caco-2/Ec472 group showed a slow and progressive loss of the scale-free status without its restoration at the end of the time interval here studied. These results contribute for a better understanding of the molecular mechanism involved in STEC pathogenicity associated to HUS. The transcriptomic profiles of Caco-2 cells during interaction with STEC strain Ec472/01 were obtained. The time-series adopted equal intervals of 7.5 minutes along 3 hours. We performed a sliding-window analysis to investigate temporal gene co-expression network (GCN) variation along 3 hours of enterocyte-bactria interaction.