Syphilis

Habitat

T. pallidum subsp. pallidum causes the sexually transmitted disease syphilis. This fastidious spirochete is an obligate parasite of humans; i.e. humans are its only natural habitat. The incidence of syphilis in the United States has decreased dramatically in recent years, but the disease remains a major health problem in many areas of the world. Untreated syphilis has primary (local), secondary (disseminated), and tertiary (chronic) stages, and infection can persist for the lifetime of the patient. Closely related organisms cause endemic syphilis (T. pallidum subsp. endemicum), yaws (T. pallidum subsp. pertenue), and pinta (T. carateum).

Biology

T. pallidum is one of the few pathogenic bacteria that has not be cultivated in vitro, although limited multiplication can be obtained in a tissue culture system. It is a microaerophilic organism, but the mechanism of oxygen utilization is unknown. Another unusual feature of the bacterium is the extremely low density of proteins in its outer membrane. This property may decrease the number of immune targets on its outer surface, leading to its description as a 'stealth' pathogen.

Sequencing Plan

The genome of T. pallidum subsp. pallidum was sequenced in 1998, and consists of a single circular chromosome with ~1,138,006 base pairs and a G + C content of 52.8%. Mycoplasma are the only bacteria known to have smaller genomes. Of the 1,041 open reading frames, only 55% have predicted biologic functions based on sequence similarities. Consistent with its fastidious nature, the T.  pallidum genome is largely devoid of genes involved in the synthesis of amino acids, nucleic acid bases, vitamins, and fatty acids. A family of 12 T. pallidum repeat (tpr) genes and a handful of other genes with a possible relationship to pathogenesis may hold clues regarding the ability of this pathogen to invade virtually any tissue and to cause long-term infection and disease.

The genome of a second syphilis causing strain, SS14, was sequenced and published in 2008. This strain is far removed from Nichols in both the date and location of its isolation. These strains appear to represent two major lineages of syphilis causing strains. We are also sequencing a third syphilis isolate, Dallas.

References for Treponema pallidum subsp. pallidum

• Complete Genome Sequence of Treponema pallidum, the Syphilis Spirochete. Fraser, C.M. et al. Science 281:375-388, 1998.
• Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays. Matejková P, Strouhal M, Smajs D, Norris SJ, Palzkill T, Petrosino JF, Sodergren E, Norton JE, Singh J, Richmond TA, Molla MN, Albert TJ, Weinstock GM. BMC Microbiol. 8:76, 2008.

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Contacts

Name	Affiliation
Patrick Minx	The Genome Institute, Washington University School of Medicine

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