[2] T. pallidum can enter the host through mucosal membranes or open lesions in the skin and is primarily spread through sexual contact.

T. pallidum's lack of both a tricarboxylic acid cycle and processes for oxidative phosphorylation results in minimal metabolic activity.

Glucose can be used not only as a primary carbon source but also in glycolytic mechanisms to generate ATP needed to power the bacterium given its minimal genome.

[6] The unique outer membrane structure and minimal expression of surface proteins of T. pallidum has made vaccine development difficult.

[10] Genes TprC, TprI, and the 5' flanking region of tpp15 can be used to differentiate between the three subspecies based on DNA fragment lengths and location of bands in gel electrophoresis.

[9] Treponema pallidum was first microscopically identified in syphilitic chancres by Fritz Schaudinn and Erich Hoffmann at the Charité in Berlin in 1905.

These include details such as its low protein content, its fragility, and that it contains fewer gene sequences related to other gram negative outer membranes.

[24] Treponema's reputation as a "stealth pathogen" is primarily due to this unique OM structure, which serves to evade immune detection.

[27] The many different types of Tpr include TprA, TprB, TprC, TprD, and TprE, but variability of TprK is the most relevant due to the immune escape characteristics it allows.

In this way, fragments of the seven variable regions (V1–V7), by nonreciprocal recombination, present in TprK and the 53 donor sites of TprD can be combined to produce new structured sequences.

[37][38] TprK antigen variation can help T. pallidum to evade a strong host immune reaction and can also allow the reinfection of individuals.

This process mainly happens in TprF, TprI, TprG, TprJ, and TprL, and it consists of a reversible expansion or contraction of polymeric repeats.

[39] With development, new discoveries about T. pallidum's requirements for growth and gene expression may occur and in turn, yield research beneficial for the treatment and prevention of syphilis, outside of a host.

[42] The challenge likely stems from the organism's strong adaptation to residing in mammalian tissue, resulting in a reduced genome and significant impairments in metabolic and biosynthetic functions.

[44] T. pallidum is not obtainable in a pure culture, meaning that this sequencing played an important role in filling gaps of understanding regarding the microbes' functions.

[21] T. pallidum was found to rely on its host for many molecules typically provided by biosynthetic pathways, and it is missing genes responsible for encoding key enzymes in oxidative phosphorylation and the tricarboxylic acid cycle.

[41] The recent sequencing of the genomes of several spirochetes permits a thorough analysis of the similarities and differences within this bacterial phylum and within the species.

In a few cases, the disease exits latency and enters a tertiary phase, in which destructive lesions of skin, bone, and cartilage ensue.

[54] The helical structure of T. p. pallidum allows it to move in a corkscrew motion through mucous membranes or enter minuscule breaks in the skin.

In more severe cases, it may gain access to the host by infecting the skeletal bones and central nervous system of the body.

[55] The causative agent of yaws is Treponema pallidum pertenue, which is transmissible by direct physical contact between infected people.

[56] Yaws is not sexually transmitted, and occurs in tropical, humid environments of Africa, Pacific Islands, Asia and South America.

[59][57] Yaws appears as skin lesions, usually papules, commonly on the lower extremities, but present in other areas such as the arms, trunk and hands.

[61][60] Yaws is treated with antibiotics such as azithromycin and benzathine penicillin-G.[62] Bejel is caused by Treponema pallidum endemicum and is a disease is that endemic in hot and dry climates.

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,[71] and because T. pallidum outer membrane proteins have not been unambiguously identified.

[74][75] In the last century, several prototypes have been developed, and while none of them provided protection from the infection, some prevented bacteria from disseminating to distal organs and promoted accelerated healing.