The intracellular life of chlamydiae.

The ability to cause persistent infection is one of the major characteristics of all chlamydial species in their appropriate hosts. Persistent infection with Chlamydia trachomatis and Chlamydia pneumoniae has been implicated in the pathogenesis of many chronic diseases, some initially not thought to be infectious, including pelvic inflammatory disease, arthritis, asthma, and atherosclerosis. Chlamydiae have a unique developmental cycle with morphologically distinct infectious and reproductive forms: elementary (EB) and reticulate bodies (RB). Chlamydiae appear to circumvent the host endocytic pathway and inhabit a nonacidic vacuole that is dissociated from late endosomes and lysosomes. Chlamydiae also have been demonstrated to enter a persistent state after treatment with cytokines such as interferon-gamma (IFN-gamma), treatment with antibiotics, or restriction of certain nutrients, or to enter this state spontaneously under certain culture conditions. While the organism is in the persistent state, metabolic activity is reduced, and the organism is often refractory to antibiotic treatment. Ultrastructural analysis of IFN-gamma-treated C pneumoniae demonstrates atypical inclusions containing large reticulate-like aberrant bodies with no evidence of redifferentiation into EBs. Persistent C pneumoniae infection appears to be associated with continued expression of genes associated with DNA replication but not with those genes involved with bacterial cell division. The latter observation may explain the appearance of the large abnormal RBs seen in ultrastructural studies. Studies of the association of chlamydiae with chronic disease have been hampered by difficulties in diagnosing chronic, persistent infection with the organism, which, in turn, render determining the efficacy of antibiotic therapy very difficult.