EGR1 is an early response transcription factor that can be induced by different stimuli. Here, we show that several strains of bacteria upregulate EGR1 expression in epithelial cells during the initial colonization of the host. For all the bacterial strains that induced EGR1 expression the maximal induction was observed at 2 h except for N. gonorrhoea occurring at 4 h. The host response is independent of adhesion levels, Gram-staining type and pathogenicity of the bacteria, but dependent on host cell contact and bacterial viability. In the assays to examine the role of cell type specificity in the upregulation of EGR1 it was observed that EGR1 was induced at different levels. However, the strongest response in the induction of EGR1 was mainly observed in the epithelial cells originating from the natural colonization site of the bacteria, indicating that the process is cell type specific. Using chemical inhibitors and RNA silencing we were able to identify β1-integrins, EGFR and ERK1/2 as the main signaling molecules mediating the EGR1 upregulation by bacteria. However, for some bacterial strains a possible role for other host signaling pathways was observed (Figure 6).