Type III secretion systems and disease

Abstract

Type III secretion systems (T3SSs) are complex bacterial structures that provide gram-negative pathogens with a unique virulence mechanism enabling them to inject bacterial effector proteins directly into the host cell cytoplasm, bypassing the extracellular milieu. Although the effector proteins vary among different T3SS pathogens, common pathogenic mechanisms emerge, including interference with the host cell cytoskeleton to promote attachment and invasion, interference with cellular trafficking processes, cytotoxicity and barrier dysfunction, and immune system subversion. The activity of the T3SSs correlates closely with infection progression and outcome, both in animal models and in human infection. Therefore, to facilitate patient care and improve outcomes, it is important to understand the T3SS-mediated virulence processes and to target T3SSs in therapeutic and prophylactic development efforts.

FIG. 1.

The T3SS apparatus consists of rings that provide a continuous path across the inner (IM) and outer (OM) bacterial membranes, including the peptidoglycan layer (PGN). A needle-like structure associates with the outer membrane ring and projects from the bacterial surface. Considering the hollow tube-like morphology of the needle, an attractive theory is that the effector proteins are transported through the hollow center of this structure.

FIG. 2.

T3SS effector functions of pathophysiologic importance. Type III secretion effectors have been implicated in a variety of critical pathogenic behaviors. These virulence strategies have specific consequences in disease pathogenesis in the infected host.