Chlamydia trachomatis is one of the most common bacterial pathogens and is the etiological agent of debilitating sexually transmitted and ocular diseases in humans. The organism is an obligate intracellular prokaryote characterized by a highly specialized biphasic developmental cycle. We have performed genomic transcriptional analysis of the chlamydial developmental cycle. This approach has led to the identification of a small subset of genes that control the primary (immediate-early genes) and secondary (late genes) differentiation stages of the cycle. Immediate-early gene products initiate bacterial metabolism and potentially modify the bacterial phagosome to escape fusion with lysosomes. One immediate early gene (CT147) is a homolog of the human early endosomal antigen-1 that is localized to the chlamydial phagosome; suggesting a functional role for CT147 in establishing the parasitophorous vacuole in a nonfusogenic pathway. Late gene products terminate bacterial cell division and constitute structural components and remodeling activities involved in the formation of the highly disulfide cross-linked outer-membrane complex that functions in attachment and invasion of new host cells. Many of the genes expressed during the immediate-early and late differentiation stages are Chlamydia-specific and have evolutionary origins in eukaryotic lineages.T he Chlamydia trachomatis bacterium is an obligate intracellular pathogen of humans that primarily infects columnar epithelial cells of the ocular and genital mucosae. Chlamydial infections of the eye and genital tract have a significant impact on human health worldwide, causing trachoma, the leading cause of preventable blindness, and sexually transmitted diseases (STD) that include pelvic inflammatory disease and tubal factor infertility (1, 2). Chlamydial STDs are also risk factors in cervical squamous cell carcinoma (3) and HIV infection (4, 5).C. trachomatis has a small genome of Ϸ1 Mb encoding 893 chromosomal and 8 plasmid ORFs that share significant homology in both gene structure and order among strains that infect human and animal hosts (6, 7). Two distinguishing characteristics of this pathogen are its developmental cycle and predilection for causing persistent infections (8). The developmental cycle consists of infectious and noninfectious stages that exhibit unique morphological, biochemical, and biological properties. The infectious elementary body (EB) is a metabolically inactive particle with a rigid, disulfide cross-linked outer membrane (OM) (9-12) that enables the EB to attach to and enter host cells (13-15). After host cell entry, the EB is localized to a phagosome, and the primary differentiation process is initiated. This developmental process involves the commencement of bacterial metabolism and the conversion of the EB to the intracellular replicating form of the organism, termed the reticulate body (RB).At the very early stage of infection (1-3 h) the parasite exerts profound effects on the host. Through an unknown mechanism, dependent on both ba...

Elementary bodies (EB) of Chlamydia trachomatis serotypes C, E, and L2 were extrinsically radioiodinated, and whole-cell lysates of these serotypes were compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Autoradiography of the polypeptide profiles identified a major surface protein with an apparent subunit molecular weight of 39,500 that was common to each C. trachomatis serotype. The abilities of nonionic (Triton X-100), dipolar ionic (Zwittergent TM-314), mild (sodium deoxycholate and sodium N-lauroyl sarcosine), and strongly anionic (SDS) detergents to extract this protein from intact EB of the L2 serotype were investigated by SDS-PAGE analysis of the soluble and insoluble fractions obtained after each detergent treatment. Only SDS readily extracted this protein from intact EB. Sarkosyl treatment selectively solubilized the majority of other EB proteins, leaving the 39,500-dalton protein associated with the Sarkosyl-insoluble fraction. Ultrastructural studies of the Sarkosyl-insoluble EB pellet showed it to consist of empty EB particles possessing an apparently intact outer membrane. No structural evidence for a peptidoglycanlike cell wall was found. Morphologically these chlamydial outer membrane complexes (COMC) resembled intact chlamydial EB outer membranes. The 39,500-dalton outer membrane protein was quantitatively extracted from COMC by treating them with 2% SDS at 60°C. This protein accounted for 61% of the total COMC-associated protein, and its extraction resulted in a concomitant loss of the COMC membrane structure and morphology. The soluble extract obtained from SDS-treated COMC was adsorbed to a hydroxylapatite column and eluted with a linear sodium phosphate gradient. The 39,500-dalton protein was eluted from the column as a single peak at a phosphate concentration of approximately 0.3 M. The eluted protein was nearly homogeneous by SDS-PAGE and appeared free of contaminating carbohydrate, glycolipid, and nucleic acid. Hyperimmune mouse antiserum prepared against the 39,500-dalton protein from serotype L2 reacted with C. trachomatis serotypes Ba, E, D, K, Ll, L2, and L3 by indirect immunofluorescence with EB but failed to react with serotypes A, B, C, F, G, H, I, and J, with the C. trachomatis mouse pneumonitis strain, or with the C. psittaci feline pneumonitis, guinea pig inclusion conjunctivitis, or 6BC strains. Thus, the 39,500-dalton major outer membrane protein is a serogroup antigen of C. trachomatis organisms. Chlamydia are obligate intracellular bacteria These findings suggest both biochemical and characterized by a unique and complex growth structural similarities between chlamydial and cycle. Phylogenetically, the chlamydiae are gram-negative bacterial outer membranes. The closely related to gram-negative organisms. In outer membrane of gram-negative bacteria has particular, both gram-negative bacteria and been intensely investigated with respect to its chlamydiae have outer membranes that respond composition and function (4). Unique proteins, similarly to ...

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