Recent advances in understanding and managing Chlamydia trachomatis infections

Abstract

Worldwide, Chlamydia trachomatis infections rank among the most common sexually transmitted infections (STI), and cause notable reproductive morbidity in women. Although advances in highly accurate and non-invasive diagnostic testing have allowed for better estimation of the burden of disease-especially the asymptomatic state-we still lack a true point-of-care test, and many infections go undetected and untreated. Moreover, limited resources and effort for managing sexual partners of those in whom infection is actually identified comprise a major challenge to control. Here, we review the current state of understanding of this common infection, and efforts to control it.

Figure 1.. Developed Chlamydial inclusion

Images of developed Chlamydia trachomatis inclusions in human epithelial cells. (A) Immunofluorescent image demonstrating Chlamydia reticulate bodies (green) located near the periphery of the inclusion at 30 hours post infection. The inclusion can be seen to be pressed up next to the cell nucleus (blue). (B) Electron micrograph of a similar inclusion at 40 hours post infection with reticulate bodies next to the inclusion membrane as well as elementary and intermediate bodies within the inclusion. Copyright © American Society for Microbiology, Infection and Immunity, 68, 2000, 360-367, and doi: 10.1128/IAI.68.1.360-367.2000

Figure 2.. Chlamydia trachomatis life cycle

The bi-phasic chlamydial growth cycle involves transformation between two distinct forms: the elementary body (EB) and the reticulate body (RB). The metabolically inactive but highly infectious EB attaches to columnar epithelial cells and is internalized within a host cell membrane-bound phagosome (A). During early stages of the life cycle, 1 to 10 hours post infection (hpi), the vesicle migrates to a perinuclear location near the Golgi apparatus (B). It is during this migration that the nascent phagocytic vesicle begins to be modified by Chlamydia-produced inclusion membrane proteins to form a parasitophorous vacuole termed an inclusion. It is also during this time period that the EB differentiates into the RB, which is the metabolically active and the replicative form. At 10 to 16 hpi, the RB begins to divide by binary fission (C). Accumulating RBs are located on the periphery of the inclusion membrane (IM), allowing type III secretory system (T3SS) needle-like structures (injectisomes) to penetrate the IM to secrete effector proteins into the cytosol which manipulate host-cellular functions, including signal transduction pathways (16 to 24 hpi). (D) Division continues as the inclusion expands, and between 24 and 36 hpi, the RBs begin to asynchronously differentiate back into EBs (E). At 36 to 48 hpi, most of the RBs have converted back to the infectious EB form preparing for release and reinfection (F). During very late stages, the infectious EBs escape the cell by lysis through proteolytic processes or by a process of extrusion (G). Reinfection then occurs, initiating new cycles of infection (H).