Treponema pallidum

Treponema pallidum subsp. pallidum is a gram-negative, motile, spirochaetes human pathogen in the spirochete family.

T. pallidum subsp. pallidum is the causative agent of syphilis. Syphilis is a multistage infectious disease that can be transmitted between sexual partners through active lesions or from an infected woman to her fetus during pregnancy.

Syphilis has a worldwide distribution (e.g., Africa has a high incidence) and affects all countries and continents. The stages of syphilis have been classified based on clinical findings leading to treatment and follow-up.

Syphilitic primary lesions may go unnoticed primarily because of their well-documented painlessness and when they occur in hard-to-see body sites (e.g., cervix, pharynx, or anus/rectum). In addition, the lesions may be misdiagnosed because of the rather uncharacteristic aspect and the lack of familiarity of physicians with the expressions of syphilis.

Secondarily, syphilis may manifest itself by exanthema, which may go unnoticed by the patient or mimic extensive disease.

Note: Treponema pallidum subsp. pallidum is completely sensitive to penicillin, although this antibiotic has been used to treat syphilis infections for seven decades. Standard treatment of uncomplicated syphilis with parenteral benzathine penicillin G is highly effective at all stages. Resistance to many antibiotics (e.g., macrolide and clindamycin resistance) has been reported in several countries.

Phylo-genomic, pan-genomic, core-genomic and singleton analyses reveal the close association between all strains of T. pallidum. Based on genome plasticity analysis, differences in the presence/absence of pathogenicity islands (PAIs) and genomic islands (GIs) can be detected on a subsp. basis. Some genes related to lipid and amino acid biosynthesis are found to be present only in the subsp. of T. pallidum, compared to T. pallidum subsp. endemicum and T. pallidum subsp. pertenue. The subspecies T. pallidum subsp. endemicum and T. pallidum subsp. pertenu are so similar that they cannot be distinguished serologically. They are antigenically cross-reactive (Jaiswal AK et al. 2020). Their morphology is also indistinguishable. In the 1980s, very limited genetic diversity was found among these pathogen species.Later, it was demonstrated that the genomes of syphilis, yaws and bejel treponemes have an overall similarity of 97-100% and the molecular organization is also identical. This evidence suggests that only small genetic changes in key genes between these organisms are responsible for the reported differences in disease pathogenesis. When looking at the genes in PAIs and GIs, it is noticeable that there are no pathogenicity islands in any of the subspecies. Genes present in pathogenicity islands (PAIs) or genomic islands (GIs) of subspecies pallidum are absent in subspecies endemicum and pertenue (Jaiswal AK et al. 2020).

The spread of venereal syphilis is global. The World Health Organization (WHO) estimates that there are 12 million new cases of syphilis annually, and the total number of cases of Yaws, Bejel, and Pinta (the endemic treponematoses) is about 2.5 million worldwide, although good epidemiological data are not available on this. Infections caused by T. pallidum are characterized by periods of active clinical disease interspersed with episodes of asymptomatic latent infections, and can cause lifelong infections in untreated individuals (Centurion-Lara A et al. 2006; Nyatsanza F et al. 2016)

The nature of T. pallidum is highly invasive. As shown by the course of syphilis infections, Treponema pallidum subsp. pallidum crosses the placental, endothelial and blood-brain barriers in the early phase of infection. However, understanding of the mechanisms responsible for the wide dissemination ability of T. pallidum is still very limited. Transmission of T. pallidum is characterized by direct skin contact and primary cutaneous lesion. It is favored by a damaged skin surface. Scratching or rubbing these damaged areas of the body may facilitate the spread of the lesions over the body. In contrast, endemic syphilis is an acute infection. Primary lesions of endemic syphilis can be seen in children between the ages of 2 and 15 years in dry and arid climates. The route of transmission is not known, but it is thought that infection may occur through mucosal and skin contact, including through shared eating or drinking vessels. Analysis of genome plasticity shows differences in the presence and absence of some genomic regions compared to subspecies.

The persistently high rate of syphilis worldwide, despite the availability of inexpensive and effective treatment, presents the most compelling argument for the need to develop a new and effective vaccine against syphilis. Despite the WHO initiative to eliminate congenital syphilis worldwide, intensive public health control directed at syphilis has been undertaken to reduce the incidence; however, this has not been successful to date. The reasons for the failure are multifactorial.

1. Centurion-Lara A et al. (2006) Molecular differentiation of Treponema pallidum subspecies. J Clin Microbiol 44:3377-3780.
2. Jaiswal Arun Kumar et al. (2020) The pan-genome of Treponema pallidum reveals differences in genome plasticity between subspecies related to venereal and non-venereal syphilis BMC Genomics 21: 33.
3. Nyatsanza F et al (2016) Syphilis: presentations in general medicine. Clin Med (Lond) 16:184-188.
4. Mitja O et al (2013) Advances in the diagnosis of endemic treponematoses: yaws, bejel, and pinta. PLoS Negl Trop Dis 7:e2283.
5. Radolf JD et al (2016) Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen. Nat Rev Microbiol 14:744-759.