The project, funded by the National Institute of Allergy and Infectious Diseases (NIAID), was a collaboration between scientists led by George M. Weinstock, Ph.D., and Steven J. Norris, Ph.D., at the University of Texas Health Science Center in Houston, and Claire M. Fraser, Ph.D., and colleagues at The Institute for Genomic Research in Rockville, Md. They report their findings in the July 17, 1998, issue of Science.

A serious, potentially fatal sexually transmitted disease, syphilis once caused widespread epidemics and is still a major cause of illness and death around the world. People with syphilis lesions also are at higher risk for HIV infection. Although reported syphilis cases in the United States are at an all-time low, outbreaks still occur especially in inner cities and the rural South. Syphilis can be treated with injections of penicillin or other antibiotics - but the early symptoms can be mild or absent, so that many people do not seek treatment when they first become infected.

The new genetic map of T. pallidum should make it easier for scientists to fill some remaining gaps in detection, treatment and prevention. A major problem for researchers has been the inability to grow the organism in the laboratory. The genetic map identifies genes that are present or absent in the bacterium's metabolic pathways. "This critical information will allow us to develop better drugs, a continuous laboratory culture system and a specific diagnostic test," says Penelope J. Hitchcock, D.V.M., chief of the sexually transmitted diseases branch at NIAID.

Adds NIAID Director Anthony S. Fauci, M.D., "Completion of this project is an extraordinary boost for efforts to develop a protective vaccine."

Syphilis is difficult to diagnose, treat and prevent:

• DIAGNOSIS:
  Symptoms can be mild or absent in the early stages, and early symptoms mimic those of many other diseases. Moreover, interpreting blood tests can be difficult - the tests can give false negative results for up to three months after infection - and repeated tests are often needed to confirm the diagnosis. "For example, with the current screening test, people who have yaws will test positive for syphilis," says Dr. Hitchcock. "In addition, we need a specific test that will diagnose congenital syphilis."

  Scientists can use the genetic blueprint for T. pallidum to devise diagnostic tests that are more specific, more accurate and easier to use.

• TREATMENT:
  Syphilis is treated with injections of penicillin or other antibiotics. About 10 percent of the population is allergic to penicillin; others do not respond to the usual doses and may need repeated injections. Easy-to-administer treatments that do not require an injection are needed, especially for use in developing countries.

  The genetic blueprint for the syphilis bacterium suggests targets for new, more specific antibiotics.

• PREVENTION:
  As for other sexually transmitted diseases, preventing syphilis requires constant vigilance, such as using condoms during intercourse and avoiding contact with an infected person's open sores. Moreover, for syphilis as well as some other sexually transmitted diseases, the male condom is only partially protective. That is because the sores can be in places that are not covered by the condom.

  Thus preventing syphilis requires extensive screening and treatment. A vaccine would be the easiest, most practical and effective method of prevention, and is especially needed to prevent new infections in high-risk U.S. populations and in developing countries.

  The genome sequence for T. pallidum reveals the existence of 12 membrane (surface) proteins that could be tested in experimental vaccines. One or more of these surface components might stimulate the immune system to respond to an invasion of T. pallidum when an uninfected person is exposed to syphilis.

"The genome sequence represents an encyclopedia of information on this elusive bacterium," says Dr. Weinstock. "We can now figure out ways to disarm its defenses through vaccines, identify it quickly through new diagnostic tests and eliminate it with specific, targeted antibiotics."

NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.

Reference:
CM Fraser, et al. Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 281:375-387 (1998).