Elusive microorganism may cause urethritis.

Researchers have been trying to figure out the disease-causing role of the mysterious microbe Mycoplasma genitalium for more than a decade. Now, a team of British scientists has evidence that this bug may underlie certain cases of urethritis, an infection of the tube (urethra) that drains urine from the bladder. They report their findings in the Sept. 4 LANCET.

The history of this research effort traces back to the discovery of a previously unknown microorganism in the genitourinary tract of two men suffering from nongonococcal urethritis (NGU). NGU, as its name suggests, is an infection with no link to the sexually transmitted Neisseria gonorrhoeae. In the June 13, 1981 LANCET, a U.S.-British research team, led by Joseph G. Tully of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., and David Taylor-Robinson of the Clinical Research Center in Harrows, England, reported culturing this new mycoplasma, which they later named M. genitalium.

NGU is typically caused by another organism -- Chlamydia trachomatis. Yet, the researchers knew that in many men, C. trachomatis doesn't cause this painful condition. They speculated that in such cases, the newly discovered M. genitalium might prove responsible. But since the mycoplasma was extraordinarily difficult to culture, the researchers could only wonder about their hypothesis.

With the advent of new molecular techniques for studying tricky organisms, the British contingent, led by Taylor-Robinson, decided to take another look at M. genitalium. He and his colleagues recruited 103 men who had NGU and compared them to 53 controls, men who had no such infection. The scientists collected samples of urethral fluid and used a powerful new technique called polymerase chain reaction (PCR) to locate DNA from any M. genitalium that might be present in those samples. PCR uses DNA probes to home in on and amplify tiny fragments of genetic material from the target organism.

The team's study shows a statistically significant association between the presence of M. genitalium and NGU, says coauthor Patrick J. Horner, also at the Clinical Research Center. Indeed, 23 percent of the men with this type of urethritis were infected with M. genitalium, as opposed to just 6 percent of the controls. That association holds whether or not C. trachomatis is present, Horner says.

"These findings suggest that the association of M. genitalium with NGU is likely to be causal," the researchers say.

Further evidence that this bug actually causes NGU comes from a 1986 study, also conducted by Taylor-Robinson and Tully. When the researchers exposed the urethras of chimpanzees to M. genitalium, the animals developed an infection that resembles the NGU that afflicts humans. The researchers used chimpanzees as a model because it would be unethical to infect humans with a microorganism thought to cause disease, Tully notes.

However, it remains possible that the association between M. genitalium and urethritis is due to chance, Horner cautions. Further study must prove that this organism actually causes urethritis in men, he says.

Because M. genitalium has been so difficult to study, not much is known about this organism or how it spreads from person to person, Horner says. "The epidemiology of this organism needs to be properly defined," he adds, noting that it is possible that M. genitalium is spread via sexual contact.

M. genitalium might also play a role in pelvic inflammatory disease (PID), a sexually transmitted infection of the pelvic organs in women that is usually caused by C. trachomatis. Some women with PID show no evidence of C. trachomatis infection, and Horner wonders whether M. genitalium will prove the culprit in such cases, as it has in male urethritis. Left untreated, PID can cause scarring of the fallopian tubes and infertility.