Tarp and Arp: How Chlamydia induces its own entry.

C hlamydia species have been known to cause human disease since antiquity. Chlamydia trachomatis is the leading cause of preventable blindness (Trachoma) in developing nations and sexually transmitted diseases and noncongenital infertility in the Western world (1). Chlamydia psittaci causes illnesses in psatticine birds and occasionally humans by accident (Psittacosis). More recently, Chlamydia pneumoniae has been recognized as a significant cause of upper and lower respiratory infections. An intriguing association between seropositivity to C. pneumoniae and chronic human diseases, particularly atherosclerosis, has been observed, although causal effect has yet to be definitively demonstrated (2). The rapid progress in understanding microbial pathogenesis afforded by the exploitation of bacteria genetics has, until recently, left chlamydiae behind due to the inability to stably introduce DNA into this obligate intracellular pathogen and the inability to grow this bacteria ex vivo. However, through recent advances in host cell biology, some of the intimate secrets and tricks of this enigmatic but fascinating pathogen are being revealed. In this issue of PNAS, Hackstadt and coworkers (3) now add another chapter into the fascinating story of C. trachomatis. Chlamydia species undergo a biphasic developmental cycle (ref. 4 and Fig. 1). The infectious hardy, spore-like, and metabolically inert extracellular form [elementary body (EB)] induces its own uptake by a diverse range of both nonphagocytic and phagocytic cultured cells, including insect cells, epithelial cells, endothelial cells, and macrophage and monocyte-derived cell lines (Fig. 1. A–D). Once internalized in a membrane-bound compartment (the chlamydial inclusion), the EB transforms into a larger and more conventional bacterial form [the reticulate body (RB); Fig. 1E] that translocates through a dyneindependent mechanism to the peri-Golgi region (5) and replicates by binary fission (Fig. 1F). Through unknown signals, the RBs reconvert to EBs after 24–72 h (Fig. 1G) and are released from the host cell, poised to infect adjacent cells or be spread to new hosts (Fig. 1H).