Syphilis, caused by the bacterium Treponema pallidum subsp. pallidum (TPA) is considered a re-emerging disease with over 5.6 million cases worldwide. Despite causing severe life-threatening infections, very little is known about the basic biology of TPA. The goal of this research proposal is to link in vitro and in vivo cultivation to genomic approaches to provide unique insights into the gene expression and epigenetic profiles of this pathogen. We will characterize differential transcriptomic responses of TPA and characterize how the transcriptomic responses correlate with the DNA methylation pattern. This should provide valuable information for the understanding of the basic biology of pathogenic treponemes that has not been previously studied.