The type III cytotoxins of Yersinia and Pseudomonas aeruginosa that modulate the actin cytoskeleton

Abstract

Initial studies of how bacterial toxins modulate the actin cytoskeleton have focused primarily on the mode of action of these toxins. More recently, studies have addressed the molecular interactions of these toxins with host cell signaling pathways and how toxins modulate cellular physiology. Although each individual toxin has a unique mode of action, general themes have started to emerge between bacterial pathogens. During the course of an infection, many pathogenic bacteria produce toxins that target the actin cytoskeleton and its regulatory proteins. Toxins can either act as positive regulators promoting the assembly of filamentous actin structures or, alternatively, as negative regulators promoting actin filament disassembly. Modulation of the actin cytoskeleton facilitates various infectious processes critical for the success of the pathogen. Intracellular bacteria such as Salmonella typhimurium utilize toxins to promote both assembly and disassembly of the actin cytoskeleton during the infection process. Temporal regulation of toxin activities results in internalization of the bacterium by epithelial cells into specialized vacuoles permissive for growth. In contrast, Yersinia utilizes actin modulating toxins to block internalization by professional antigen-presenting cells such as macrophages and dendritic cells. Modulation of the immune response through the production of actin-regulating toxins appears to be a common approach adopted by several extracellular pathogens. Thus the repertoire of actin-modifying toxins produced by various species is specifically tailored to facilitate the lifestyle of the pathogen. The presence of multiple toxins that modulate the activation state of actin shows the importance of interfering with the cytoskeleton to neutralize the host's innate immune system for the survival and growth of Yersinia and P. aeruginosa. © Springer-Verlag 2005.