NEWS RELEASE, 10/22/98 Chlamydia genome sequenced for first time, revealing unusual biology, says UC Berkeley researcher

By Kathy Scalise, Public Affairs

BERKELEY -- University of California, Berkeley, researchers and their colleagues report in Science this week the first complete sequencing of the Chlamydia trachomatis genome. This bacteria infects humans and causes both chlamydial genital tract infections, which are sexually transmitted, and trachoma, a leading cause of preventable blindness, said UC Berkeley Public Health Professor Richard Stephens, lead author on the Oct. 23 Science paper. Stephens said sequencing of the Chlamydia genome revealed a wealth of knowledge about the poorly understood organism. "We know more about Chlamydia from this one study than we knew before from 40 years of research," he said. "We found new targets on the surface that could help us develop a vaccine and we found new proteins that interact with the host and could help us with diagnostics." While trachoma is more common in other parts of the world, chlamydial genital tract infections are the most commonly reported disease of any kind in the U.S., sexually transmitted or otherwise, Stephens said. It is most often contracted in the U.S. by teenagers between the ages of 14 and 19. Though the disease is prevalent in both sexes, women suffer its most serious effects, including "chronic pelvic pain, ectopic pregnancy and involuntary sterilization," said Stephens. Stephens said finding better ways to diagnose this disease, which the new findings could make possible, is important since such infections often show no symptoms before permanent damage occurs. "From 60 to 70 percent of new chlamydial infections go undiagnosed in young women," he said. "It is a very significant disease agent in teenage girls." Stephens said what was learned about how this organism operates "is just tremendous," he said. "I think for the scientific community studying Chlamydia, it's a huge advance." Chlamydia trachomatis, as well as its variants in other species, is an unusual organism since it is not closely related, or phylogenetically similar, to other families of bacteria, Stephens said. It probably diverged from the rest long ago and has evolved along different lines. "These are pathogens that have been in humans a long time," Stephens said. Not much was previously known about the complex biology of C. trachomatis in part because it "only grows in human cells," said Stephens. "We had no methods of doing genetics with this organism." Sequencing of the more than one-million base pairs in its genome revealed some unexpected biology. For instance, though the organism lacks many biosynthetic capabilities, it can perform key steps and interconversions of metabolites from mammalian host cells, not previously suspected. The research team also discovered an unusually large number of genes which appear to have descended not from prokaryotic ancestors - bacteria and blue-green algae - but from eukaryotes, which are more complex organisms such as plants and animals. Stephens said this may be related to the pathogen's long evolutionary history with its various host cells. "It is possible," said the report, "that the evolution of chlamydiae as intracellular parasites started with an opportunistic interaction with amoebal hosts," from which the bacteria acquired the 'plant-like' genes. If this theory is correct, only later did the organism diverge into the major chlamydial genera and adapt to its various vertebrate hosts such humans, sheep and birds. Besides Stephens, other researchers on the project included staff scientist Claudia Lammel and graduate student Wayne Mitchell of UC Berkeley's Program in Infectious Disease; Sue Kalman, Jun Fan, Rekha Marathe and Ronald W. Davis of the DNA Sequencing and Technology Center at Stanford University; L. Aravind, Roman L. Tatusov and Eugene V. Koonin of the National Center for Biotechnology Information at the National Library of Medicine, National Institutes of Health; and Lynn Olinger and Qixun Zhao of the Francis I. Proctor Foundation at UC San Francisco. Their research was funded by the Sexually Transmitted Disease Branch of the National Institute for Allergy and Infectious Diseases.