Venereal syphilis was first reported in Europe in the late 1400s, coincident with the return of Columbus from the New World. The disease quickly reached epidemic proportions in Europe and spread across the world during the early 16th century. Syphilis is characterized by multiple clinical stages and long periods of latent, asymptomatic infection. The primary infection is localized, but organisms rapidly disseminate and cause manifestations throughout the body. Although effective therapies have been available since the introduction of penicillin, syphilis remains an important global health problem.

Treponema pallidum is the causative agent of syphilis. It is a spirochete, a helical to sinusoidal bacterium with outer and cytoplasmic membranes, a thin peptidoglycan layer, and periplasmic flagella. Mechanisms of T. pallidum pathogenesis are poorly understood. No known virulence factors have been identified, and the outer membrane is mostly lipid with a paucity of proteins. Consequently, existing diagnostic tests for syphilus are suboptimal, and no vaccine against T. pallidum is available.

Because of its importance as a human pathogen, TIGR sequenced the genome of T. pallidum subsp. pallidum (strain Nichols) by the whole genome random sequencing method. The T. pallidum genome is a circular chromosome of 1,138,006 base pairs containing a total of 1041 predicted open reading frames.