The intestinal ecosystem is comprised of bacteria that are both beneficial and detrimental to human health. The opportunistic pathogens residing within the gastrointestinal tract typically function as commensal members of the human microbiota. However, in certain circumstances these bacteria are able to escape the intestine and cause severe infections throughout the host. This dissertation defines the transcriptional adaptation within macrophages and elucidates the role of transcriptional regulation during pathogenicity in the opportunistic pathogen, Enterococcus faecalis.