ABSTRACTVirulent genes present inEscherichia coli (E. coli)can cause significant human diseases. These enteropathogenicE. coli(EPEC) and enterotoxigenicE. coli(ETEC) isolates with virulent genes show different expression levels when grown under diverse laboratory conditions. In this research, we have performed differential gene expression analysis using publicly available RNA-seq data on three pathogenicE. colihybrid isolates in an attempt to characterize the variation in gene interactions that are altered by the presence or absence of virulent factors within the genome. Almost 26.7% of the common genes across these strains were found to be differentially expressed. Out of the 88 differentially expressed genes with virulent factors identified from PATRIC, nine were common in all these strains. A combination of Weighted Gene Co-Expression Network Analysis and Gene Ontology Enrichment Analysis reveals significant differences in gene co-expression involving virulent genes common among the three investigated strains. The co-expression pattern is observed to be especially variable among biological pathways involving metabolism-related genes. This suggests a potential difference in resource allocation or energy generation across the three isolates based on genomic variation.