Combination antibiotics for the treatment of Chlamydia-induced reactive arthritis: is a cure in sight?

Abstract

The inflammatory arthritis that develops in some patients subsequent to urogenital infection by the obligate intracellular bacterial pathogen Chlamydia trachomatis, and that induced subsequent to pulmonary infection with C. pneumoniae, both have proved difficult to treat in either their acute or chronic forms. Over the last two decades, molecular genetic and other studies of these pathogens have provided a good deal of information regarding their metabolic and genetic structures, as well as the detailed means by which they interact with their host cells. In turn, these insights have provided for the first time a window into the bases for treatment failures for the inflammatory arthritis. In this article we discuss the biological bases for those treatment failures, provide suggestions as to research directions that should allow improvement in treatment modalities, and speculate on how treatment regimens that currently show promise might be significantly improved over the near future using nanotechological means.

Figure 1. The chlamydial developmental cycle

EB: Elementary body; RB: Reticulate body. Reproduced with permission from [86], © Cambridge University Press (2006).

Figure 2. Morphology of chlamydial inclusions

(A) McCoy cells infected for 36 h with Chlamydia trachomatis. Fluorescent signal represents chlamydial inclusions which are filled with reticulate bodies and elementary bodies (arrows). (B) Cells infected with C. trachomatis for the same length of time but Penicillin G was added at 12 h postinfection to induce persistent infection. The large, aberrant reticulate bodies are representative of persistent infection. In both cases, cells were fixed with absolute methanol and stained with a fluorescein-isothiocyanate-conjugated anti-chlamydial lipopolysaccharide antibody (Pathfinder™, BioRad). Images at original magnification, 400×, were captured with ImagePro (MediaCybernetics, Bethesda, MD, USA).