Treponema pallidum is a gram-negative spirochaete bacterium. There are at least four known subspecies: T. pallidum pallidum, which causes syphilis; T. pallidum pertenue, which causes yaws; T. pallidum carateum, which causes pinta; and T. pallidum endemicum, which causes bejel.

T. pallidum pallidum is a motile spirochaete that is generally acquired by close sexual contact, entering the host via breaches in squamous or columnari. The organism can also be transmitted to a fetus by transplacental passage during the later stages of pregnancy, giving rise to congenital syphilis. The helical structure of T. pallidum pallidum allows it to move in a corkscrew motion through viscous mediums such as mucus. It gains access to host's blood and lymph systems through tissue and mucus membranes.

The subspecies causing yaws, pinta, and bejel are morphologically and serologically indistinguishable from T. pallidum pallidum (syphilis); however, their transmission is not venereal in nature and the course of each disease is significantly different.

In the July 17, 1998 issue of the journal Science, a group of biologists reported how they sequenced the genome of T. pallidum. The recent sequencing of the genomes of several spirochetes permits a thorough analysis of the similarities and differences within this bacterial phylum. Treponema pallidum subsp. pallidum has one of the smallest bacterial genomes at 1.14 million base pairs (Mb) and has limited metabolic capabilities, reflecting its adaptation through genome reduction to the rich environment of mammalian tissue.

There is no vaccine for syphilis. The outer membrane of T. pallidum has too few surface proteins for an antibody to be effective. Efforts to develop a safe and effective syphilis vaccine have been hindered by uncertainty about the relative importance of humoral and cellular mechanisms to protective immunity and the fact that T. pallidum outer membrane proteins have not been unambiguously identified.