Chlamydia trachomatis is the etiologic agent of a diverse group of clinical syndromes including trachoma, a chronic inflammatory disease of the eye, and sexually transmitted diseases. Chlamydiae are bacterial obligate intracellular parasites that undergo a unique biphasic life cycle involving cell types adapted for extracellular survival and dispersal and for intracellular growth. The regulatory mechanisms governing this complex life cycle are poorly understood. We have characterized a pair of unique proteins with homology to eukaryotic histone H1. Histone H1 homologs are rare among prokaryotes. C. trachomatis is unusual in that it possesses two histone analogs. The genes are expressed only during the late stages of the chlamydial life cycle concomitant with the reorganization of chlamydial reticulate bodies into elementary bodies suggesting that the histone analogs play a role in the condensation of chlamydial chromatin during intracellular differentiation. Expression of the 18 kDa histone analog, Hc1, in recombinant hosts induces a compaction of the bacterial chromatin that ultrastructurally resembles events late in the chlamydial developmental cycle. The Hc1 protein therefore appears to play a major role in the condensation of the chlamydial nucleoid characteristic of mature EBs and in doing so contributes to an overall down regulation of gene expression. Effects on DNA structure may play a significant role in the regulation of gene expression during chlamydial development. Understanding the controlling mechanisms for gene expression and differentiation may suggest unique methods of interrupting parasite replication.
