Chlamydia uncloaked.

T he word Chlamydia is derived from the Greek meaning cloaklike mantle. The term was coined based on the incorrect conclusion that Chlamydia are intracellular protozoan pathogens that appear to cloak the nucleus of infected cells. Thus, this genus designation is symbolic of the difficulties encountered in discovering the true nature of these important pathogens. It is now known that the chlamydiae are actually prokaryotic organisms, and what was originally thought to be the hooded cloak is in fact a cytoplasmic vesicle containing numerous individual organisms and is termed an inclusion (1). There has been a great deal of interest and effort devoted to understanding more about chlamydiae because it is clear that Chlamydia trachomatis infections continue to be a problem both in the developing world, as a leading cause of preventable blindness (trachoma), and in industrialized countries, as a major sexually transmitted disease (STD) pathogen and significant cause of pelvic inflammatory disease and tubal factor infertility in women (2). The association of genital infections by C. trachomatis with increased risk for cervical cancer and HIV transmission reinforces the need to gain deeper appreciation of the means and mode of chlamydial pathogenesis (3). The more recent recognition of Chlamydia pneumoniae as an important community-acquired respiratory pathogen and its association with common chronic aff lictions such as asthma and cardiovascular disease provide additional documentation of the importance for improved understanding of the pathogenic potential for these organisms (4). Lack of a gene transfer system for chlamydiae has hampered definitive pathogenesis investigations for these organisms. Most studies have used traditional cell biology and biochemical approaches, often coupled with microscopic or ultrastructural observations for visual validation of the results (5). Studies of this kind have provided useful insights on chlamydial growth and development, mechanisms of pathogenesis, and generation of immune responses, but, in general, work on chlamydiae has been hindered by the more descriptive restrictions imposed by the limitations in available technology. Reverse genetics has occasionally yielded functional confirmation for a few chlamydial gene products, but these types of studies depend on producing, cloning, and expressing a chlamydial gene or set of genes in a heterologous system, relying on sufficient similarity between the chlamydial gene and the heterologous organism to permit complementation for appropriate mutants (6). When reverse genetic studies work, the results can be gratifying, but relying on this strategy imposes severe restrictions in the actual amount of use-