Syphilis: using modern approaches to understand an old disease

Abstract

Syphilis is a fascinating and perplexing infection, with protean clinical manifestations and both diagnostic and management ambiguities. Treponema pallidum subsp. pallidum, the agent of syphilis, is challenging to study in part because it cannot be cultured or genetically manipulated. Here, we review recent progress in the application of modern molecular techniques to understanding the biological basis of this multistage disease and to the development of new tools for diagnosis, for predicting efficacy of treatment with alternative antibiotics, and for studying the transmission of infection through population networks.

Figure 1. The natural history of untreated syphilis in immunocompetent individuals.

Percentages of individuals developing to specific stages as well as time intervals are based on information in references , , and (based on data from refs. –148).

Figure 2. Gene conversion as the mechanism of antigenic variation of TprK in T. pallidum.

Variant DNA segments located adjacent to the tprD gene non-reciprocally recombine with the variable regions (V1-V7) of the tprK gene in the expression site to generate new TprK mosaic proteins.

Figure 3. T. pallidum strain types identified throughout the world.

The strain type information, years of collection, and the frequency of each strain type from each location are based on information in references , , –, –, , and .