The Chlamydial Type III Secretion Mechanism: Revealing Cracks in a Tough Nut

Abstract

Present-day members of the Chlamydiaceae contain parasitic bacteria that have been co-evolving with their eukaryotic hosts over hundreds of millions of years. Likewise, a type III secretion system encoded within all genomes has been refined to complement the unique obligate intracellular niche colonized so successfully by Chlamydia spp. All this adaptation has occurred in the apparent absence of the horizontal gene transfer responsible for creating the wide range of diversity in other Gram-negative, type III-expressing bacteria. The result is a system that is, in many ways, uniquely chlamydial. A critical mass of information has been amassed that sheds significant light on how the chlamydial secretion system functions and contributes to an obligate intracellular lifestyle. Although the overall mechanism is certainly similar to homologous systems, an image has emerged where the chlamydial secretion system is essential for both survival and virulence. Numerous apparent differences, some subtle and some profound, differentiate chlamydial type III secretion from others. Herein, we provide a comprehensive review of the current state of knowledge regarding the Chlamydia type III secretion mechanism. We focus on the aspects that are distinctly chlamydial and comment on how this important system influences chlamydial pathogenesis. Gaining a grasp on this fascinating system has been challenging in the absence of a tractable genetic system. However, the surface of this tough nut has been scored and the future promises to be fruitful and revealing.

Biochemical and Structural Insights into Microtubule Perturbation by CopN from Chlamydia pneumoniae

“…We have also determined the 1.2 Å resolution structure of pCopN and mapped the surface interacting with tubulin. The structure confirms CopN as the Chlamydia homolog of the Yersinia YopN protein, as proposed (12,13); as such, it seems likely that it serves as a plug of the type III secretion system of this bacteria (14) and is secreted during infection, albeit in small amounts (15,16). Taken together, the natural abundance of tubulin (17) and its affinity for pCopN mean that, when secreted in the cytoplasm, pCopN will be bound to tubulin.…”

Chlamydia trachomatis Tarp Harbors Distinct G and F Actin Binding Domains That Bundle Actin Filaments

“…The invasive EB is formed in the middle to late stages of the intracellular development cycle as the RBs differentiate back to EBs and are packed with metabolites and proteins designed to facilitate extracellular survival and reinfection (4,5). Additional infectious cycles arise from EBs that are released and disseminate from infected tissues (6).…”

Disulfide Bonding within Components of the Chlamydia Type III Secretion Apparatus Correlates with Development

“…The T3SS has been referred to as a "molecular syringe" and comprises a multiprotein basal apparatus spanning both bacterial membranes, an exogenous needle filament composed of a single protein, and a terminal multimeric protein forming a tip complex (22,24). In Chlamydia spp., activity of this secretion system is uniquely linked to the developmental cycle (6,34,44). Since a preformed T3SS exists in EBs (16) and secretion activity begins as early as invasion (10,23), T3S components must be able to negotiate the highly cross-linked envelope.…”

“…Since a preformed T3SS exists in EBs (16) and secretion activity begins as early as invasion (10,23), T3S components must be able to negotiate the highly cross-linked envelope. It is possible that T3S apparatus proteins may themselves represent integrated members of the supramolecular disulfidebonded complex (6). In this study, we investigate the possibility that developmentally responsive disulfide bonding occurs among T3S apparatus proteins of the outer Chlamydia envelope.…”