Survey of Genomes - Treponema pallidum

In this episode from a survey of genomes, Daijah Sek from the 2019 Hiram College Genetics course walks us through the genome of the syphilis pathogen Treponema pallidum.

My name is Daijah Sek, and on today’s episode I will be discussing Treponema pallidum which many of you may already be familiar with. In 1905, scientists Schaudinn and Hoffman identified this spiral-shaped bacterium as a causative agent of syphilis. However, we now suspect with more recent research done that this may have originated and been present as far back as in the Columbus era in the 1400s in Europe. It’s subspecies can cause yaws and bejel in restricted regions of the world. Though they are more constrained to tropical climates.

As said by Fraser et al., Treponema pallidum has been a difficult organism to study experimentally because it is completely dependent on a mammalian host for sustained growth and viability. If the exact conditions are not met, the organism cannot be studied. The genomic sequence of T. pallidum brings about a great deal of useful information that would be unlikely to find by any other approach. A more complete understanding of the biochemistry of this organism derived from genome analysis may provide a foundation for the development of a culture medium for T. pallidum, which opens up the possibility of future genetic studies.

As we know, syphilis is a relatively common STI/STD that is still around today. While we have an effective treatment of penicillin or other appropriate antibiotics should a patient be allergic, it is still useful to study this organism and to care about it because of its presence today and because there is still much more to learn about what can be done for people who have syphilis in more serious forms such as latent and tertiary where fatality is on the table.
In 1998, Fraser et al. sequenced the T. pallidum genome and determined that it hast 1,138,006 base pairs. This organism contains a single circular chromosome containing 1,041 predicted coding sequences or open reading frames.
In 1999, Centurion-Lara et al. studied Treponema pallidum’s major sheath protein trp K which is a target of opsonic antibody and the protective immune response. It is predicted to have a cleavable signal peptide and is located in the outer membrane of the bacterium. With their research done on rabbits, they hypothesized that this gene family is important to pathogenesis and immunity of syphilis infection. They identify that treponema pallidum is able to cause a multistage disease and establishes life-long infections and that it is important to understand that through protective immunity.

In 2000, only two years after the T. pallidum genome was sequenced, Subramanian et al did a study on comparative genome analyses of Treponema pallidum organism with Borrelia burgdorferi which is another pathogenic spirochete that is known to be the causing agent of Lyme disease. This team was able to compare the genomes and gain insight to the organism’s evolutionary trends and adaptive strategies. This can better help scientists to understand the organism in order to more effectively treat as well as even prevent the diseases. They specifically were able to identify metabolic and signaling pathways that are specifically in pathogens and great targets for therapeutic intervention. Fun fact: this study used the tool BLAST that we have all become very familiar with. The team was also able to identify new protein families in these spirochetes which with further research, they believe can be a resourceful way to study pathogen-host interactions.

References:
Fraser, Claire M., et al. “Complete Genome Sequence of Treponema Pallidum, the Syphilis Spirochete.” Science, American Association for the Advancement of Science, 17 July 1998, science.sciencemag.org/content/281/5375/375.full.

Centurion-Lara, A et al. “Treponema pallidum major sheath protein homologue Tpr K is a target of opsonic antibody and the protective immune response” Journal of experimental medicine vol. 189,4 (1999): 647-56.

George M. Weinstock, John M. Hardham, Michael P. McLeod, Erica J. Sodergren, Steven J. Norris, The genome of Treponema pallidum: new light on the agent of syphilis, FEMS Microbiology Reviews, Volume 22, Issue 4, October 1998, Pages 323–332, https://doi.org/10.1111/j.1574-6976.1998.tb00373.x

Subramanian, G et al. “Comparative genome analysis of the pathogenic spirochetes Borrelia burgdorferi and Treponema pallidum” Infection and immunity vol. 68,3 (2000): 1633-48.

https://www.cdc.gov/std/syphilis/treatment.htm