TIGR Researchers Reveal Tricks of Common Sexually Transmitted Infection
January 11, 2007
It's the world's most common non-viral sexually transmitted infection. There are an estimated 8 million cases of trich — pronounced "trick" — a year in North America and 170 million cases worldwide. But in a cover article in the January 12, 2007, issue of Science , researchers reveal many of trich's tricks.
An international consortium led by investigators at the Institute for Genomic Research (TIGR) is publishing a draft genome sequence of T. vaginalis , the cause of trich. The paper includes genome analyses that pave the way for new forms of treatment and improvement of existing ways of dealing with this irritating, persistent, and sometimes serious sexually transmitted infection.
"Now that we have the T. vaginalis genome sequence and analyzed its many unique features, we have new ways of studying the biology of an organism that continues to be ignored as a public health issue despite the high number of trichomoniasis cases in the world," said Trichomonas Genome Project director Jane Carlton, first author of the paper, who is now at the Department of Medical Parasitology, New York University School of Medicine. The study was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
The findings reveal mechanisms that help T. vaginalis resist existing therapies. They also home in on targets for new drugs and new diagnostic techniques and identify repeating sequences that can be used for epidemiology and population studies.
T. vaginalis has the largest genome so far identified in a eukaryotic parasite, an estimated 160 Mb and more predicted genes than the human genome. The researchers speculate that an enormous genome expansion occurred when an ancestor of T. vaginalis moved from the G.I. tract to the urogenital tract. A bigger genome also meant a bigger cell. Size would have given the parasite an evolutionary advantage, because a bigger cell could increase surface area for colonizing the vagina — a necessary step to infection. A larger parasite could also consume more bacteria, especially the "good" lactobacilli that normally keep the vagina too acid for T. vaginalis to thrive. So bigger was better because it helped T. vaginalis remodel its environment.
Repetitive gene families have expanded to more than 65% of the T. vaginalis genome, unprecedented in single-celled eukaryotes, according to the researchers. The parasite's genome contains many families of repeats, present in thousands of copies. Within each family the repeats are nearly identical, with very little polymorphism. Such a genome has never been described before and made genome assembly particularly difficult.
Only one class of drugs, the 5-nitroimidazoles such as Flagyl, is approved for treatment of trichomoniasis, and T. vaginalis is developing resistance to them. The researchers identified mechanisms that may help the parasite become resistant. These discoveries could lead to ways of slowing the resistance process.
The researchers identified more than 800 genes that code for candidate surface proteins that probably help T. vaginalis adhere to cells in the host's urogenital tract. Many of the proteins are similar to proteins of other pathogens, notably Chlamydia, which causes another sexually transmitted infection. They also identified genes coding for cell-destroying factors that are probably released when the parasite contacts the host. The parasite also possesses one of the largest known "degradomes," 400 genes that code for peptidases. These protein-smashing enzymes are potential virulence factors, vaccine candidates, and drug targets.
T. vaginalis is one of a small group of eukaryotes that does not possess classical mitochondria. Instead it uses organelles known as hydrogenosomes to produce ATP and molecular hydrogen. T. vaginalis hydrogenosomes contain no genetic material, and their origins have been controversial. The researchers found evidence supporting a common evolutionary origin for mitochondria, hydrogenosomes, and other organelles known as mitosomes. The researchers also found evidence that predicts a new function for hydrogenosomes: amino acid metabolism.
ABOUT TRICHOMONAS VAGINALIS AND TRICHOMONIASIS:
An estimated 8 million cases of trichomoniasis (usually called "trich", pronounced "trick") occur every year in North America , with a total of 170 million cases annually around the world. Trich is often accompanied by other sexually transmitted infections like gonorrhea and chlamydia. Trich is transmitted during unprotected sex; condoms can prevent transmission. It is also transmitted occasionally through direct contact with surfaces such as shared bedding and towels, and even toilet seats.
The standard treatment for trich is Flagyl, but the single-celled parasite that causes the disease, Trichomonas vaginalis , is becoming increasingly resistant to this drug, making development of new medicines a high priority.
Infected men frequently have no symptoms, and sometimes women are symptom-free as well. Thus diagnosis and treatment can be difficult. Symptoms include a frothy yellow-green discharge from the vagina or penis, itching of the vulva, and burning inside the penis. Trich can be passed from an infected woman to her infant during delivery. Trich can increase the risk for HIV acquisition, and has been associated with premature labor and low birth-weight babies.
Diagnosis is through testing of vaginal secretions for women, and urethral secretions for men. The US Centers for Disease Control and Prevention does not require local health departments to report cases of the disease, unlike several other less common sexually transmitted infections such as gonorrhea.
CONTACT: Lead author: Professor Jane Carlton, TIGR/NYU School of Medicine jane.carlton@med.nyu.edu; phone: 1-212-263-4377
Collaborators: Professor Patricia Johnson, UCLA
johnsonp@ucla.edu; 1-310-825-4870
Dr. Robert Hirt, Newcastle University
R.P.Hirt@ncl.ac.uk; phone: +44-191-246-4805