Demonstrates Conserved Proteomic and Transcriptomic Responses When Co-cultured With Human INT 407 and Caco-2 Epithelial Cells.

Major foodborne bacterial pathogens, such as , have devised complex strategies to establish and foster intestinal infections. For more than two decades, researchers have used immortalized cell lines derived from human intestinal tissue to dissect -host cell interactions. Known from these studies is that virulence is multifactorial, requiring a coordinated response to produce virulence factors that facilitate host cell interactions. This study was initiated to identify proteins that contribute to adaptation to the host cell environment and cellular invasion. We demonstrated that responds to INT 407 and Caco-2 cells in a similar fashion at the cellular and molecular levels. Active protein synthesis was found to be required for to maximally invade these host cells. Proteomic and transcriptomic approaches were then used to define the protein and gene expression profiles of co-cultured with cells. By focusing on those genes showing increased expression by when co-cultured with epithelial cells, we discovered that quickly adapts to co-culture with epithelial cells by synthesizing gene products that enable it to acquire specific amino acids for growth, scavenge for inorganic molecules including iron, resist reactive oxygen/nitrogen species, and promote host cell interactions. Based on these findings, we selected a subset of the genes involved in chemotaxis and the regulation of flagellar assembly and generated deletion mutants for phenotypic analysis. Binding and internalization assays revealed significant differences in the interaction of chemotaxis and flagellar regulatory mutants. The identification of genes involved in adaptation to culture with host cells provides new insights into the infection process.