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Thursday, January 11, 2007
Scientists Sequence Genome of Parasite Responsible for Common Sexually Transmitted Infection
Researchers have decoded the genetic makeup of the parasite that causes trichomoniasis, one of the most common sexually transmitted infections (STIs), revealing potential clues as to why the parasite has become increasingly drug resistant and suggesting possible pathways for new treatments, diagnostics and a potential vaccine strategy. The genome sequencing project, funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), is detailed in the January 12 issue of Science.
“The progress that continues to be made in deciphering the genomes of organisms, such as the Trichomonas vaginalis parasite, helps to further our collective scientific understanding of these organisms, so that we can better address public health issues,” says NIH Director Elias A. Zerhouni, M.D.
“By better understanding the genetic makeup of the Trichomonas vaginalis parasite that causes trichomoniasis, we can target our efforts to developing the most effective medicines to treat the infection and potentially create a way to prevent infection altogether,” says NIAID Director Anthony S. Fauci, M.D.
Trichomoniasis is a sexually transmitted infection that affects both men and women and results in roughly 7.4 million new cases in the United States each year, according to the U.S. Centers for Disease Control and Prevention.
In women, trichomoniasis infection commonly occurs in the vagina, resulting in heavy yellow-green or gray vaginal discharge, vaginal odor, discomfort during sexual intercourse and urination, irritation and itching of the genital area and, in rare cases, lower abdominal pain. In men, trichomoniasis is most common in the urethra; however, infected men often do not have symptoms. Those that do may experience irritation inside the penis, mild discharge, or a slight burning sensation after urination or ejaculation. Symptoms in both men and women generally appear within five to 28 days of exposure to the parasite.
Both men and women with trichomoniasis have an increased susceptibility to HIV infection and may transmit HIV to their sexual partners. Pregnant women with trichomoniasis may deliver a low birthweight (less than five pounds) or premature infant. Although the prescription drugs metronidazole and tinidazole usually cure trichomoniasis, drug resistance has become an increasing concern.
T. vaginalis is pear-shaped with thread-like flagella that propel its movement. Once it attaches to cells lining the host’s urinary or genital tract, it flattens out and begins to ingest the cells, as well as white and red blood cells, causing direct damage to the urinary and vaginal tissues and resulting in inflammation. T. vaginalis also consumes bacteria that may be present in the urinary and genital areas, including the bacteria necessary for maintaining a normal healthy environment in the vagina. As a result, women infected with trichomoniasis become more susceptible to becoming infected by HIV and other STIs.
In generating the genetic blueprint for the parasite, researchers were surprised to find such a large and highly repetitive genome comprising nearly 26,000 predicted genes as determined by computer models and previously sequenced parasitic genomes. Repetitive genes accounted for roughly 65 percent of the genome.
“Parasites generally have smaller amounts of DNA than non-parasitic organisms, but in this case, there was ten times as much DNA than we originally thought there would be,” says lead author Jane M. Carlton, Ph.D., who led the project while at The Institute for Genomic Research (TIGR), a not-for-profit research organization based in Rockville, Maryland. Dr. Carlton is now an associate professor in the Department of Medical Parasitology at New York University’s School of Medicine.
Although it is not entirely clear why the genome is so large and repetitive, researchers theorize that the parasite evolved over time, previously inhabiting the intestine and later moving to the urogenital tract, which resulted in increased cell size and, subsequently, a considerably expanded genome.
The researchers also discovered more than 150 instances where bacterial genes may have transferred into the parasite’s genome, suggesting that bacteria may have influenced the development of the parasite’s metabolism. The decoded genome also revealed 800 genes for surface proteins that likely enable T. vaginalis to adhere to cells in the urinary and genital tracts and cause infection. Additionally, the researchers were able to analyze proteins thought to be linked to the parasite’s hydrogenosome--its energy source and the target of the two drugs approved to treat trichomoniasis--and identified possible ways the parasite may become resistant to these medications. Understanding how T. vaginalis causes infection and developing methods to prevent it could also help curb the transmission of other STIs often found in connection with trichomoniasis, including chlamydia and gonorrhea, according to the researchers.
“Although trichomoniasis is very prevalent as a sexually transmitted infection, it has not received the attention given to other STIs,” says Carlton. “Women are the population most affected by it, yet routine gynecological check-ups do not test for this particular infection, and it’s not an STI that generally requires public health notification under state statutes. By better understanding the parasite’s genetic structure, we hope to better understand how best to prevent and/or treat the infection it causes.”
For an image of the T. vaginalis parasite, see http://www3.niaid.nih.gov/news/newsreleases/2007/TvaginalisParasite_photo.htm.
News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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JM Carlton et al. Draft genome of the sexually transmitted pathogen Trichomonas vaginalis. Science DOI: 10.1126/science.1132894 (2007).