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.

Figure 1

Cartoon of the type III secretion system showing the needle apparatus in contact with the host cell.

Figure 2

(A) Salmonella T3SS basal structure that spans the outer membrane (OM), the periplasm, and the inner membrane (IM) and is formed by (B) rings of InvG (red), PrgH (purple), and PrgK (blue). (C) Structures of proteins that form the T3SS basal body: EPEC EscC, EPEC EscJ,Salmonella PrgH, and Shigella MxiG.

Figure 3

(A) Structures of needle protomers Salmonella PrgI^CΔ5 (CΔ5, deletion of five C-terminal residues), PrgI* (a functional V65A/V67A double mutant), PrgI polymerized into needles,Shigella MxiH^CΔ5, MxiH polymerized into needles, and Burkholderia BsaL^CΔ5. Regions that adopted β-strands upon needle assembly are colored green. (B) Atomic model of the Salmonella needle derived by solid-state NMR showing that the N-terminus of PrgI faces the exterior.

Figure 4

Structure of tip proteins from (A) Y. pestis, (B) Burkholderia pseudomallei, (C) S. flexneri, and (D) S. typhimurium.

Figure 5

(A) Structures of the N-terminal domains of the Shigella IpaB and Salmonella SipB translocon proteins. (B) Cocrystal structures of IpgC, SycD, and PcrH chaperones bound to peptides derived from their cognate translocon proteins.