A HUS-associated STEC expressing a dicA transcriptional module is related to gene network dysregulation in Caco-2

We conducted comparative gene co-expression network (GCN) analyses of two O113:H21 STEC strains: EH41, reference strain, isolated from hemolytic-uremic syndrome patient in Australia, and Ec472/01, isolated from cattle feces in Brazil. These strains were cultured in fresh or in Caco-2 cell conditioned media. GCN analyses were also accomplished for cultured Caco-2 cells exposed to EH41 or Ec472/01. Differential transcriptome profiles for EH41 and Ec472/01 were not significantly changed by exposure to fresh or Caco-2 conditioned media. Conversely, global gene expression comparison of both strains cultured in conditioned medium revealed a gene set exclusively expressed in EH41, which includes the dicA putative virulence factor regulator. Network analysis showed that this set of genes constitutes an EH41 specific transcriptional module. The GCNs of Caco-2 cells exposed to EH41 or to Ec472/01 presented a major transcriptional module containing many hubs related to inflammatory response that was not found in the GCN of control cells. Moreover, EH41 seems to cause gene network dysregulation in Caco-2. Therefore, EH41 virulence may be derived from its capacity for dysregulating enterocyte genome functioning and its enhanced enteric survival due to slow growth. [EH41]: Caco-2 transcriptomic profiles after 3 hrs of interaction with STEC strain EH41 and without interaction (control) were compared in order to identify differentially expressed transcripts [EC472]: Caco-2 transcriptomic profiles after 3 hrs of interaction with STEC strain EC472/01 and without interaction (control) were compared in order to identify differentially expressed transcripts [COND]: STEC transcriptomic profiles after 3 hrs incubation in conditioned Caco-2 cell medium: STEC strain EH41 (isolated from patient with HUS) and STEc strain EC472/01 (isolated from cattle) were compared in order to identify differentially expressed transcripts [FRESH]: STEC transcriptomic profiles after 3 hrs incubation in fresh medium: STEC strain EH41 (isolated from patient with HUS) and STEc strain EC472/01 (isolated from cattle) were compared in order to identify differentially expressed transcripts