Structure and Biophysics of Type III Secretion in Bacteria

Abstract

Many plant and animal bacterial pathogens assemble a needle-like nanomachine, the type III secretion system (T3SS), to inject virulence proteins directly into eukaryotic cells to initiate infection. The ability of bacteria to inject effectors into host cells is essential for infection, survival, and pathogenesis for many Gram-negative bacteria, including Salmonella, Escherichia, Shigella, Yersinia, Pseudomonas, and Chlamydia spp. These pathogens are responsible for a wide variety of diseases, such as typhoid fever, large-scale food-borne illnesses, dysentery, bubonic plague, secondary hospital infections, and sexually transmitted diseases. The T3SS consists of structural and nonstructural proteins. The structural proteins assemble the needle apparatus, which consists of a membrane-embedded basal structure, an external needle that protrudes from the bacterial surface, and a tip complex that caps the needle. Upon host cell contact, a translocon is assembled between the needle tip complex and the host cell, serving as a gateway for translocation of effector proteins by creating a pore in the host cell membrane. Following delivery into the host cytoplasm, effectors initiate and maintain infection by manipulating host cell biology, such as cell signaling, secretory trafficking, cytoskeletal dynamics, and the inflammatory response. Finally, chaperones serve as regulators of secretion by sequestering effectors and some structural proteins within the bacterial cytoplasm. This review will focus on the latest developments and future challenges concerning the structure and biophysics of the needle apparatus.

Type III secretion systems: the bacterial flagellum and the injectisome

“…Further details on the structure of injectisomes and flagella can be obtained from dedicated recent reviews [30,[50][51][52][53].…”

Visualization and characterization of individual type III protein secretion machines in live bacteria

“…The needle is capped at its end by the tip complex, which is thought to coordinate the activation of the secretion machine upon contact with target cells (9,10). Because the needle complex can be isolated in a manner suitable for single-particle cryo-electron microscopy, its organization at the quasi-atomic level is known (11)(12)(13)(14)(15)(16)(17)(18). Passage of the secreted proteins through the inner membrane requires the export apparatus, which is composed of a group of poly-topic inner membrane proteins located at the center of the needle complex base (19).…”

The inner rod protein controls substrate switching and needle length in a Salmonella type III secretion system

“…These machines exert their function by delivering effector proteins into target cells with the capacity to modulate a variety of cellular processes for the benefit of the pathogens or symbionts that encode them (4). Type III secretion systems (TTSSs), comprising >20 proteins, are among the most complex protein secretion machines so far identified (5,6). Salmonella Typhimurium, a cause of gastroenteritis in humans, encodes two TTSSs within its pathogenicity islands 1 (SPI-1) and 2 (SPI-2), which are essential for pathogenicity (7,8).…”

“…TTSSs consist of the envelope-associated needle complex, which mediates the passage of the secreted proteins through the bacterial envelope, and several cytoplasmic accessory proteins, which are required for the recognition and sorting of the proteins destined to travel this pathway (5,6,9,10). The needle complex is composed of a multiring, envelope-associated base substructure, and a filament or needle seated on the base, projecting outward from the bacterial surface (9,11).…”