Oct. 23, 1998 Researchers in California supported by the National Institute of Allergy and Infectious Diseases (NIAID) have completed sequencing the Chlamydia trachomatis genome, providing new insights into chlamydial infection, the most prevalent bacterial sexually transmitted disease (STD) in the United States and a major cause of STDs worldwide. C. trachomatis also is the etiologic agent of ocular trachoma, the leading cause of preventable blindness in the developing world. A report describing the project appears in the Oct. 23, 1998 issue of Science.
This project was a collaborative effort between scientists at the University of California at Berkeley, the University of California at San Francisco, and the DNA Sequencing and Technology Center at Stanford University. Richard S. Stephens, Ph.D., M.P.H., primary investigator of the project, led the microbiology team at the University of California at Berkeley, and Ronald Davis, Ph.D., led the sequencing effort at Stanford. The sequenced genome has already been entered into a new on-line database, the STD Relational Database (http://www.stdgen.lanl.gov), funded by NIAID and designed to accelerate research on STDs.
"Their accomplishment has important implications for vaccine development," comments Anthony S. Fauci, M.D., director of NIAID. "The genome sequence has revealed surface proteins about which we knew nothing, and the organism’s unique biochemical pathways provide promising new leads for developing antibiotics."
More than 4 million new cases of chlamydial infection occur in the United States each year, and associated medical costs are estimated to exceed $2 billion. Control of chlamydial infection is complicated by the frequency of asymptomatic disease, the cost and complexity of many available diagnostic tests, and the inadequacy of prevention and control programs.
In women, 20 to 40 percent of untreated or inadequately treated chlamydial infections result in pelvic inflammatory disease (PID), an infection of the upper reproductive tract. The resulting tubal scarring leads to infertility, tubal pregnancy and chronic pelvic pain. Chlamydial infection also increases the risk for HIV infection.
Researchers have found the study of C. trachomatis challenging because unlike most bacteria, this organism only grows inside the host cell, just like a virus. Also, many aspects of C. trachomatis – its physiology, structure, developmental biology and genetics – are poorly understood. Its genome, however, has already revealed some extraordinary secrets. Over time, it appears that this bacterium has borrowed genetic information from its human hosts, and it uses this information to tap the resources of the cells and get essential nutrients that it cannot make.
"The Chlamydia trachomatis genome represents a molecular gold mine for the research community," says Dr. Stephens. "Even the establishment of a genetic system, which we can manipulate to study the organism, is within reach. This would enable scientists to use molecular tools to investigate, for example, how the organism gets inside the cells, how it causes scarring and how Chlamydia might escape the effects of antibiotic therapy."
The last few years have yielded critical advances in the battle against this devastating STD. A highly sensitive and specific urine test to diagnose the illness has been developed. The pharmaceutical industry has made a safe and effective single-dose oral therapy. NIAID-funded researchers have used these new tools to document the enormous problem in adolescent populations and to show that early screening and treatment for chlamydial infection can prevent PID.
"Despite significant progress, the more we look, the more chlamydial infections we find. Clearly we need better prevention tools if we are going to stop the spread of this silent plague," says Penelope J. Hitchcock, D.V.M., chief of NIAID's STD branch. "Of particular interest is a better understanding of the early steps in the infectious process – this knowledge will lead to vaccines to prevent PID and topical microbicides to prevent infection."
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