New insights into a persistent problem -- chlamydial infections

Abstract

Tissue tropism of clinical ocular and genital Chlamydia trachomatis strains is shown to be linked to the tryptophan synthase genotype. It is suggested that, in the presence of IFN-gamma, which depletes available tryptophan, there exist unique host-parasite interactions that may contribute to persistent chlamydial infection.

Figure 1

Chlamydial infection is initiated by the attachment of the infectious EB to the host cell, followed by entry of the EB into a membrane-bound vesicle, termed an inclusion. The inclusion evades fusion with host lysosomes, and the EB rapidly differentiates into an RB that replicates by binary fission within the inclusion. Following several rounds of replication, the RBs reorganize and form infectious EBs, which are released from the cell. Under certain conditions, such as in an inflammatory environment where IFN-γ is produced, the intracellular growth of ocular and urogenital chlamydial strains may be altered. IFN-γ induces cellular IDO, which results in a marked decrease in available tryptophan. Depletion of tryptophan either results in chlamydiae cell death or causes chlamydiae to adopt a noninfectious, nonreplicating form that retains viability (persistence). The outcome is dependent on the level and duration of tryptophan depletion and the tryptophan synthase genotype of the infecting chlamydial strain. Persistent forms of chlamydiae can redifferentiate into infectious EBs upon removal of IFN-γ and subsequent replenishing of intracellular tryptophan pools. Alternatively, even in an IFN-γ–rich environment, strains of chlamydiae that possess a functional tryptophan synthase (i.e., genital strains) may use indole (perhaps produced by local microbial flora) as a substrate for tryptophan synthesis to counter the growth inhibitory effects of IFN-γ. This model is far from complete, and the biological processes involved are likely much more complex and interrelated than depicted here. However rudimentary, though, the proposed model provides a reasonable representation of our current understanding.