Type III Secretion in Chlamydia

Type III secretion systems (T3SSs) are utilized by Gram-negative pathogens to enhance their pathogenesis. This secretion system is associated with the delivery of effectors through a needle-like structure from the bacterial cytosol directly into a target eukaryotic cell. These effector proteins then manipulate specific eukaryotic cell functions to benefit pathogen survival within the host. The obligate intracellular pathogens of the family Chlamydiaceae have a highly evolutionarily conserved nonflagellar T3SS that is an absolute requirement for their survival and propagation within the host with about one-seventh of the genome dedicated to genes associated with the T3SS apparatus, chaperones, and effectors. Chlamydiae also have a unique biphasic developmental cycle where the organism alternates between an infectious elementary body (EB) and replicative reticulate body (RB). T3SS structures have been visualized on both EBs and RBs. And there are effector proteins that function at each stage of the chlamydial developmental cycle, including entry and egress. This review will discuss the history of the discovery of chlamydial T3SS and the biochemical characterization of components of the T3SS apparatus and associated chaperones in the absence of chlamydial genetic tools. These data will be contextualized into how the T3SS apparatus functions throughout the chlamydial developmental cycle and the utility of heterologous/surrogate models to study chlamydial T3SS. Finally, there will be a targeted discussion on the history of chlamydial effectors and recent advances in the field.