Treponema pallidum

Treponema Pallidium
Scientific classification
Kingdom: Eubacteria Phylum: Spirochaetes Class: Spirochaetes Order: Spirochaetales Family: Spirochaetacae Genus: Treponema Species: T. pallidium

Description and significance

Sypihlis is a sexually transmitted disease. Treponema Pallidium is the major cause of its transmission. It is not able to survive outside and depends fully on humans as host for survival. Its has the ability to escape the human immune response and it grows for sometime and the symptoms that are come in the early stages of the onset disappear and the organism grows inside the body until it is detected and it is treated. It depends completely on the host for synthesis of everything it requires for itself. It grows slowly in the individual. It can affect all the organs of the body. It can finally cause death. People are usually treated before they reach the stage where it can be lethal. It can be transmitted from one person to the other through sexual contact or by use of drugs that are injected and from the blood of one person to another and actually by direct contact with the syphilis sores.

Genome structure

Treponema pallidum is a prokaryote with one of the smallest genomes. The organism has many processes that are similar and required for other organisms although it is dependent on the host for its survival. Like other eukaryotes it undergoes transcription, translation, replication, repair and has restriction- modification systems. Its genomic sequence is very close to that of Borrelia burgdorferi that causes Lyme Disease in humans. The total genome sequence of the organism has 1,138,006 base pairs. The number of base pairs of the predicted coding sequences or of the number of open reading frames is 1041.

In order to repair DNA, T. pallidum methods uvr exision repair, mutL/mutS mismatch repair, mut Y and dat.

The bacterium lacks type 4 topoisomerase that is involved in the process of chromosome segregation. Chromosome segregation in T. Pallidium is able to occur by another mechanism that involves binding hemimethylated DNA to the cytoplasmic membrane. The spirochete T. pallidium encodes homologs in the recF pathway that are involved in recombination.

Cell structure and metabolism

T. pallidium is a microaerophile and so it needs very little oxygen for growth. It does not have genes that code for enzymes that protect against oxygen toxicity. The enzymes are present in B. Burgdorferi and include superoxide dimutase, peroxidase or catalase. It does however have NADH oxidase which is the enzyme that utilizes oxygen in the organism.

It has an outer membrane a cytoplasmic membrane and it also consists of a thin peptidoglycan layer. Its outer membrane has relatively fewer integral membrane proteins. This permits the organism to evade the human response from the immune system.

The energy sources for T. pallidium are mainly carbohydrates like glucose, galactose and glycerol. In tissue culture systems the growth and multiplication of T. pallidium is only due to glucose, mannose and maltose. This has been an suggested due to experimental evidence. The T. pallidium has all the genes that code for enzymes that are required for the glycolytic pathway. T. pallidium has homologs of the enzymes phosphofructokinase and pyruvate kinase that are there in eubacterial organisms which use pyrophosphate for energy metabolism. It does not have any of the genes that code for substances required in the tricarboxylic acid cycle or of oxidative phosphorylation.

T.pallidium does not have a respiratory transport electron chain. ATP is therefore formed by substrate level phosphorylation and so the membrane potential is created by the reverse reaction of the enzyme ATP synthase. The ATP synthase in the T.pallidium is of the V1V0 type. It also has two operons of the V1V0 type and each contains seven genes.

Pathology

T. pallidium is the causative agent of syphilis. It is transmitted through humans and causes diseases and can cause damages and previous damage done by the organism cannot be cured. It is only transmitted sexually. It can be transmitted from mother to baby. The disease it transmitted by sexual contact and it does not spread by using things that are used by others for regular purposes such as clothes, utensils, etc. The disease is spread from one person to another by contact with syphilis sores. The sores can occur on the external anus, vagina, and internal anus and can also occur in the rectum. The primary stage of syphilis there is a chancre that is round and does not cause pain. It heals on its own and if the disease is not treated a person will go into the secondary and late phases of the disease. The sores can also occur in the mouth. Sometime it is not possible for a person to know whether the person has syphilis because sores occur in inside of the vagina and anus in males and females. So the person should be tested for syphilis. The secondary phase is associated with rash through out the body. If it is not treated the symptoms will go into the latent phase and it can cause damage to organs and it affects the coordination and affect the important organs and may even lead to death. Syphilis can be treated and the person at that time should avoid sexual contact. It requires use of antibiotics and intramuscular injection of penicillin.

The person infected with Syphilis has a higher risk of getting HIV. The spread of the disease can be prevented by using safe sex practices like the use of a condom. Use of condoms can be effective if the person uses it with care and even then the person should be careful not to come in contact with the syphilis sores of the infected person.

Neurosyphilis is a problem in patients who suffer from syphilis. It involves the Central nervous system. Tests are done by using the cerebrospinal fluid. There are four types of neurosyphilis Asymptomatic neurosyphilis, Meningovascular syphilis, General paresis and Tabes dorsalis. The last two forms are not quite common now.During Meningiovascular syphilis the person first experiences prodomal symptoms and then the person goes into the later stage. The disease can occur within 10 months or it might on an average take 7 years to be expressed. The symptoms of the prodomal stage are behavioral changes and other problems are headache, weakness, numbness and insomnia. There can also be an inflammation of the arteries and the person can also suffer from stroke because there is less blood supply from the arteries.

Current Research

The treatment for Syphilis is the use of antibiotics such as penicillin. It is however resistant to certain antibiotics such as erythromycin and azithromycin. In the past these drugs were used to cure syphilis. However patients with the problem who were treated with these two antibiotics could not be cured. The T. pallidium strain was able to become resistant to these two antibiotics due to certain mutations in its gene. The mutation was in the AG in the 23S r RNA. This gene codes for a ribosomal subunit of 50S. The mutation occurred at the point A2058G. The mutated ribosome is not able to bind to the antibiotic and so the bacteria becomes resistant to the drug. Since mutants were found and as some of the strains of the spirochete and other bacterium are resistant to the antibiotic researchers are continuously surveying the proper use of the drug. Penicillin is the the most commonly used drug for syphilis patients. Those people who are allergic to this drug are desensitized and then the the drug is given to them. Azithromycin does not treat the person who has syphilis but it is still used in places like San Francisco and the person is usually cured.

The T. pallidium is capable of evading the human immune response. It has not yet been possible to find a vaccine to prevent the disease. Some of the molecules of the bacteria were used and tested. It was found that the antibodies that are made are not effective in getting rid of infection. Recombinant genes were also made and these genes could not be very effective in curing the person. This is because the proteins made might not really get folded in their actual native forms.

B.burgdorferi is not able to escape the immune response system. So even though the two organisms are closely related T. pallidium is able to evade the response. This is because of the difference between their outer surface proteins. Unlike Lyme disease syphilis is expressed after sometime after the infection. FcRs are produces and they take the bacteria directly to the phagolysosome rather than creating the pathogen-specific immune response.

References

[1] Claire M. Fraser et all. Complete Genome Sequence of Treponema pallidum, the Syphilis Spirochete. Science Volume 281, Pages 375 -388 DOI:10.1126/ science.281.5375.375.

[2] Katz, Kenneth A. and Klausner, Jeffrey D. “Azithromycin resistance in Treponema pallidum.” “Current Opinion in infectious diseases”. Volume 21 Issue 1Pages 83-91 DOI: 10.1097/QCO.0b013e3282f44772

[3] Lafond, Rebecca E. and Lukehart, Sheila A. Biological Basis for Syphilis Clinical Microbiology Reviews, January 2006, Pages 29-49, Volume 19 doi:10.1128/CMR.19.1.29-49.2006

[4] Moore, Meagan W. “Phagocytosis of Borrelia burgdorferi and Treponema pallidum Potentiates Innate Immune Activation and Induces Gamma Interferon Production.” Infection and Immunity Volume 75 , Pages 2046-2062 doi:10.1128/IAI.01666-06