Protein delivery into eukaryotic cells by type III secretion machines

Abstract

Bacteria that have sustained long-standing close associations with eukaryotic hosts have evolved specific adaptations to survive and replicate in this environment. Perhaps one of the most remarkable of those adaptations is the type III secretion system (T3SS)--a bacterial organelle that has specifically evolved to deliver bacterial proteins into eukaryotic cells. Although originally identified in a handful of pathogenic bacteria, T3SSs are encoded by a large number of bacterial species that are symbiotic or pathogenic for humans, other animals including insects or nematodes, and plants. The study of these systems is leading to unique insights into not only organelle assembly and protein secretion but also mechanisms of symbiosis and pathogenesis.

Bioinformatic and Biochemical Evidence for the Identification of the Type III Secretion System Needle Protein ofChlamydia trachomatis

“…possess surface-localized, filamentous projections. These structures are very reminiscent of T3SS-associated needle structures that are required for the delivery of T3SS effector proteins (in conjunction with additional "translocator" proteins), presumably by bridging the gap between the bacterial envelope and an intimately associated eukaryotic membrane (19). Evidence from other T3SSs indicates that these extended filaments consist of a single protein, and yet a homolog is not readily apparent in chlamydial genomes.…”

Atomic resolution structure of the cytoplasmic domain of Yersinia pestis YscU, a regulatory switch involved in type III secretion

“…1,2 Y. pestis and many other gram-negative bacterial pathogens use a type III secretion system (T3SS) as a protein transport apparatus to inject a small number of effector proteins through a hollow needle that extends across the inner and outer bacterial membranes and into the cytosol of eukaryotic cells. [3][4][5] The effector Yops (Yersinia outer proteins) enable the pathogenic bacteria to defeat the immune response of the host by interfering with the signal transduction pathways that regulate the actin cytoskeleton, phagocytosis, apoptosis, and the inflammatory response. 6 The export apparatus consists in part of cytoplasmic and inner-membrane proteins that identify T3SS substrates and control the switching of substrate specificity during morphogenesis and hostcell contact.…”

“…6 The export apparatus consists in part of cytoplasmic and inner-membrane proteins that identify T3SS substrates and control the switching of substrate specificity during morphogenesis and hostcell contact. 3,4 YscU, an essential component of the secretion apparatus in Yersinia, is composed of 354 amino acid residues that are organized into a four-helix transmembrane N-terminal domain and a large C-terminal cytoplasmic domain separated by a long linker region that is highly conserved among YscU orthologs. 7 The cytoplasmic domain of YscU undergoes auto-cleavage of the N263-P264 peptide bond at the conserved NPTH site, resulting in an N-terminal fragment, YscU CN (residues 211-263), and a C-terminal fragment, YscU CC (residues 264-354), that remain tightly intertwined and copurify together.…”

Cytoskeleton rearrangements during Listeria infection: Clathrin and septins as new players in the game

“…The zipper mechanism is mechanistically and morphologically distinct from the trigger mechanism. Triggering bacteria such as Salmonella typhimurium or Shigella flexneri directly inject effectors into the cytosol of host cells via the type III secretion system that hijack cellular proteins involved in cytoskeleton rearrangements or signaling [Galan and Wolf-Watz, 2006;Ogawa et al, 2008]. As a result, these bacteria basically enter host cells in a process similar to macropinocytosis.…”