Treponema Pallidum

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University of Oklahoma Study Abroad Microbiology in Arezzo, Italy[1]

Etiology/Bacteriology

Taxonomy

Domain: Bacteria
Phylum: Spirochaetes
Order: Spirochaetales
Family: Spirochaetaceae
Genus: Treponema
Species: T. pallidum

Description

Treponema pallidum is a motile, spirochaete bacteria that has subspecies that can cause treponemal diseases such as syphilis, pinta, bejel, and yaws. Syphilis is caused by the subspecies T. pallidum pallidum, pinta is caused by T. pallidum carateum, bejel is caused by T. pallidum endemicum, and yaws is caused by T. pallidum pertenue. The four subspecies of T. pallidum are morphologically and serologically identical, however their course of action and transmission differs from one another. Even though T. pallidum can cause all four of these diseases, the most serious and concerning of these is syphilis. T. pallidum is a small bacterium that cannot be seen via Gram stain because it is too thin. However, it can be viewed by using dyes like Dieterle Stain (1). It can also be detected by serology tests. Syphilis is transmitted venereally while the other T. pallidum diseases are not. There were reported cases of syphilis-like symptoms dating back to the 14th and 15th centuries with a possible origin being Europe. The symptoms appear in 3 stages and include sores, rashes, latent periods, nervous system damage and eventually death. Because of the seriousness involved with syphilis, most of the research is on this disease and therefore the remainder of this page is based upon it as well.

History

There are reported cases of syphilis-like symptoms that date back to the 13th-14th century in Europe(2). However, the first treponemal diseases are theorized to have originated in East Africa. The disease is said to have migrated from Africa into Asia, Europe, and North America possibly due to the slave trade(3). Another theory is that the disease started in Europe and from there spread to Africa, Asia, and North America. It is said that a European explorer named Vasco da Gama carried the disease to Calcutta in 1498 and from there it spread to Africa and then Asia by 1520(4). There is also a possibility that syphilis cases were reported as a mistake because before 1500 there was not a distinction between syphilis and leprosy(5). However, it is important to remember that these are all just theories and there is no definitive answer for where or when Syphilis emerged. It wasn't until 1905 that the bacteria that causes syphilis was discovered by German researches. From 1932 until 1972 the Tuskegee study was conducted in order to watch the progression of the disease. By 1943 Penicillin was widely used to combat this disease. However, during World War II there was a large outbreak of syphilis cases in the U.S. where over 500,000 cases were reported per year(8)(12).

Pathogenesis

Transmission

Syphilis is transmitted venereally via direct contact with primary or secondary sores (chancres)(6). This can include anal, vaginal, or, oral contact with an infected person. Syphilis can also be transmitted congenitally from mother to child through the placenta during pregnancy. Syphilis cannot be transferred by toilet seats, swimming pools, door knobs, eating utensils, sharing clothes, etc. because it is oxygen sensitive(7)(10).

Colonization

Syphilis can only naturally grow in human hosts(12). It can attach to a wide variety of cells such as epithelial, endothelial, and fibroblastlike cells. Syphilis enters the body through a breach in the skin or mucous membranes. It can move to the blood stream, spinal fluid, and to other internal organs very rapidly via its internal flagella. This diffusion can be seen in the secondary stage of infection when the body is covered in a rash as a result of infection with the disease(10). T. pallidum attaches to cells by using adhesion molecules to "cap" the host cells.The extracellular matrix is involved in mediating the attachment of T. pallidum to the fibronectin-coated coverslips of the host cells(12).

Incubation and Infectious dose

As seen in guinea pigs, the infectious dose of Treponema pallidum is anywhere between 10 to 1,000,000 organisms. However the mean number seems to be about 100 organisms to cause infection(11). The incubation period is unusually long taking about 30-33 hours for T. pallidum to double in vivo. In a culture it takes anywhere from 30-50 hours to double. Symptoms for the primary stage of this disease can occur between 10-90 days after contact with the bacteria(12)(13). The secondary symptoms occur 2 weeks to 12 weeks after contact, the latent period is about 1 year after infection. There are three types of tertiary stage symptoms that can occur with the first being cardiac occurring 10-30 years after infection. Neurosyphilis symptoms can be seen 2-20 years after infection and Gumma can be seen 1-46 years after infection (with the mode being 15 years). There are also two types of congenital syphilis symptoms; early (onset to two years), or late (persistence to greater than two years)(14).

Virulence Factors

Syphilis has a few very important virulence factors. One factor in particular it its corkscrew shape. It's shape gives it the ability to maneuver through gel-like material which is necessary when traveling through the genital and oral cavities. This allows syphilis to enter in areas many other disease causing bacteria could not(10). Syphilis produces many lipoproteins which induces the expression of inflammatory mediators when recognized by TLR's. Treponema has three proteins with fibronectin adhesion molecules. The three molecules are named for where they were discovered in the genome sequence. Tp0155 binds to matrix fibronectin which suggests that it is functional in the blood stream. The next molecule, Tp0483, binds to both soluble and matrix fibronectin which suggests it is functional in tissues. Tp0751 is the last molecule and it binds specifically to laminin which means it can bind to laminin coated coverslips. The different protein molecules could suggest all the different types of tissues syphilis can invade and use to diffuse throughout the body. Syphilis also contains an endoflagellum located between the cytoplasmic membrane and the outer membrane. The fact that this flagella is internal makes it hard for the host immune system to completely attack the organism. The flagella is made up of several protein filaments and it is theorized that those proteins are what the immune system recognizes rather than an external flagella. Syphilis has methyl-accepting chemotaxis transmembrane proteins (MCPs) and cytoplasmic chemotaxis proteins (Che) which help it to perform chemotaxis. MCP's may have a high affinity to glucose and histidine whereas Che helps syphilis respond to nutrient gradients so it can move from tissues into the bloodstream. Syphilis has also been known to induce the production of matrix metalloproteinase-1 (MMP-1) which breaks down collagen in dermal cells. This could be how syphilis is able to penetrate tissues(12).

Treatment

Mercury, Arsenic, Penicillin, magic bullet

References

(1)http://www.princeton.edu/~achaney/tmve/wiki100k/docs/Treponema_pallidum.html
(2)http://www.news-medical.net/health/Syphilis-History.aspx
(3)http://cid.oxfordjournals.org/content/40/10/1454.full
(4)http://www.infoplease.com/cig/dangerous-diseases-epidemics/syphilis-sexual-scourge-long-history.html
(5)http://archive.archaeology.org/9701/newsbriefs/syphilis.html
(6)http://www.cdc.gov/std/syphilis/stdfact-syphilis.htm
(7)http://www.webmd.com/sexual-conditions/guide/syphilis
(8)http://www.intheknowzone.com/sexual-health-topics/syphilis/history-of-syphilis.html
(9)http://www.gendercentre.org.au/resources/polare-archive/archived-articles/syphilis.htm
(10)http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1360276/
(11)http://www.ncbi.nlm.nih.gov/pmc/articles/PMC257764/
(12)http://cmr.asm.org/content/19/1/29.full
(13)http://emedicine.medscape.com/article/229461-overview#a0104
(14)http://www.gov.mb.ca/health/publichealth/cdc/protocol/syphilis.pdf

References

[Sample reference] Takai, K., Sugai, A., Itoh, T., and Horikoshi, K. "Palaeococcus ferrophilus gen. nov., sp. nov., a barophilic, hyperthermophilic archaeon from a deep-sea hydrothermal vent chimney". International Journal of Systematic and Evolutionary Microbiology. 2000. Volume 50. p. 489-500.

Created by Rachael Acosta, student of Tyrrell Conway at the University of Oklahoma.