Abstract

The chlamydial inclusion membrane is extensively modified by the insertion of type III secreted effector proteins. These inclusion membrane proteins (Incs) are exposed to the cytosol and share a common structural feature of a long, bi-lobed hydrophobic domain but little or no primary amino acid sequence similarity. Based upon secondary structural predictions, over 50 putative inclusion membrane proteins have been identified in Chlamydia trachomatis. Only a limited number of biological functions have been defined and these are not shared between chlamydial species. Here we have ectopically expressed several C. trachomatis Incs in HeLa cells and find that they induce the formation of morphologically distinct membranous vesicular compartments. Formation of these vesicles requires the bi-lobed hydrophobic domain as a minimum. No markers for various cellular organelles were observed in association with these vesicles. Lipid probes were incorporated by the Inc-induced vesicles although the lipids incorporated were dependent upon the specific Inc expressed. Co-expression of Inc pairs indicated that some colocalized in the same vesicle, others partially overlapped, and others did not associate at all. Overall, it appears that Incs may have an intrinsic ability to induce membrane formation and that individual Incs can induce membranous structures with unique properties.

Highlights

  • Chlamydiae are obligate intracellular bacteria that are the etiologic agents of a variety of diseases affecting humans or animals

  • The initial descriptions of C. caviae and C. trachomatis inclusion membrane proteins (Incs) were of chlamydial proteins having relatively uniform distribution around the circumference of the inclusion membrane [30,31,32]

  • Chlamydiae encode a genome of only 1.04 Mbp [42], they commit approximately 4 percent of their coding capacity to a family of proteins that modify the inclusion membrane

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Summary

Introduction

Chlamydiae are obligate intracellular bacteria that are the etiologic agents of a variety of diseases affecting humans or animals. A number of other Chlamydia species are restricted to specific animal species. Despite the great diversity in disease, tissue tropism, and species specificity, the sequenced genomes of chlamydiae display a very high degree of synteny and sequence similarity. All chlamydiae share a simple developmental cycle that consists of cell types adapted for extracellular survival, the elementary body (EB), or for intracellular replication, the reticulate body (RB) [17]. The chlamydial developmental cycle takes place within a vacuole, called an inclusion, unlike that of any other known intracellular pathogens [18,19,20]. The mechanistic details of this pathway are largely unknown [21] but are clearly defined by the parasite as chlamydial transcription and translation is required for initiation of the process [22]

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