Bacterial type III secretion systems: specialized nanomachines for protein delivery into target cells

Abstract

One of the most exciting developments in the field of bacterial pathogenesis in recent years is the discovery that many pathogens utilize complex nanomachines to deliver bacterially encoded effector proteins into target eukaryotic cells. These effector proteins modulate a variety of cellular functions for the pathogen's benefit. One of these protein-delivery machines is the type III secretion system (T3SS). T3SSs are widespread in nature and are encoded not only by bacteria pathogenic to vertebrates or plants but also by bacteria that are symbiotic to plants or insects. A central component of T3SSs is the needle complex, a supramolecular structure that mediates the passage of the secreted proteins across the bacterial envelope. Working in conjunction with several cytoplasmic components, the needle complex engages specific substrates in sequential order, moves them across the bacterial envelope, and ultimately delivers them into eukaryotic cells. The central role of T3SSs in pathogenesis makes them great targets for novel antimicrobial strategies.

Keywords: bacterial pathogenesis; molecular machines; protein secretion.

Fig. 1

Needle complex structure from Salmonella typhimurium. A. Surface views of the 3D reconstruction of the cryo EM map of the S. typhimurium needle complex. The different substructures are noted. B. Surface view of a half-sectioned needle complex containing a trapped substrate within the central tunnel (119). Relevant structural details and dimensions are noted. C. Docking of the atomic structures of the different needle complex components onto the 3D cryo-EM map.

Fig. 2

Diagram of the needle complex and associated structures. A previously suggested common nomenclature (71) was used to indicate the potential localization of the different components and facilitate comparison across different systems.

Fig. 3

The tip complex of type III secretion systems. A. Crystal structures of tip proteins from different bacteria. Relevant structural features are noted. B. Conformational changes in the IpaD tip protein induced by the binding of deoxycholate, which is thought to mimic the activation event that occurs upon contact with target cells.

Fig. 4

Model for the assembly of the type III secretion needle complex and associated structures. To facilitate comparison of the assembly pathway in different type III secretion systems, a previously suggested nomenclature of the different components was used (71) (see Table 1). See text for details.

Fig. 5

Proposed models for the mechanism of substrate switching and needle length control in the assembly pathway of the needle complex. See text for details.