Invasion of epithelial cells by the obligate intracellular bacterium Chlamydia trachomatis results in its enclosure inside a membrane-bound compartment termed an inclusion. The bacterium quickly begins manipulating interactions between host intracellular trafficking and the inclusion interface, diverging from the endocytic pathway and escaping lysosomal fusion. We have identified a previously uncharacterized protein, CT622, unique to the Chlamydiaceae, in the absence of which most bacteria failed to establish a successful infection. CT622 is abundant in the infectious form of the bacteria, in which it associates with CT635, a putative novel chaperone protein. We show that CT622 is translocated into the host cytoplasm via type three secretion throughout the developmental cycle of the bacteria. Two separate domains of roughly equal size have been identified within CT622 and a 1.9 Å crystal structure of the C-terminal domain has been determined. Genetic disruption of ct622 expression resulted in a strong bacterial growth defect, which was due to deficiencies in proliferation and in the generation of infectious bacteria. Our results converge to identify CT622 as a secreted protein that plays multiple and crucial roles in the initiation and support of the C. trachomatis growth cycle. They reveal that genetic disruption of a single effector can deeply affect bacterial fitness.
The lifestyle of Chlamydiae is unique: the bacteria alternate between two morphologically distinct forms, an infectious non-replicative elementary body (EB), and a replicative, non-infectious reticulate body (RB). This review focuses on recent advances in understanding the structure and function of the infectious form of the best-studied member of the phylum, the human pathogen Chlamydia trachomatis. Once considered as an inert particle of little functional capacity, the EB is now perceived as a sophisticated entity that encounters at least three different environments during each infectious cycle. We review current knowledge on its composition and morphology, and emerging metabolic activities. These features confer resistance to the extracellular environment, the ability to penetrate a host cell and ultimately enable the EB to establish a niche enabling bacterial survival and growth. The bacterial and host molecules involved in these processes are beginning to emerge.
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