Biological basis for syphilis

Abstract

Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subsp. pallidum. Clinical manifestations separate the disease into stages; late stages of disease are now uncommon compared to the preantibiotic era. T. pallidum has an unusually small genome and lacks genes that encode many metabolic functions and classical virulence factors. The organism is extremely sensitive to environmental conditions and has not been continuously cultivated in vitro. Nonetheless, T. pallidum is highly infectious and survives for decades in the untreated host. Early syphilis lesions result from the host's immune response to the treponemes. Bacterial clearance and resolution of early lesions results from a delayed hypersensitivity response, although some organisms escape to cause persistent infection. One factor contributing to T. pallidum's chronicity is the paucity of integral outer membrane proteins, rendering intact organisms virtually invisible to the immune system. Antigenic variation of TprK, a putative surface-exposed protein, is likely to contribute to immune evasion. T. pallidum remains exquisitely sensitive to penicillin, but macrolide resistance has recently been identified in a number of geographic regions. The development of a syphilis vaccine, thus far elusive, would have a significant positive impact on global health.

FIG. 1.

Natural history of untreated syphilis, according to Gjestland (112).

FIG. 2.

Amino acid alignment of TprK showing six different sequences in the T. pallidum Sea81-4 strain harvested from a single infection. Conserved regions are indicated by black shading; V regions have white and gray shading. The V region that exhibits the greatest diversity is V6, with six different sequences; in comparison, only two different sequences are found in V1. For ease of visualization, the conserved C- and N-terminal portions of the protein and 64 amino acids of conserved sequence between V1 and V2 are truncated (//). (The GenBank accession numbers of the sequences shown are AY346063 to AY346068.)