Yersinia pestis, the infective agent of plague, has caused social devastation on a scale unmatched by any other infectious agent. Although it is not a major public health problem now, Yersinia pestis still infects rodent populations in large endemic zones, and there are cases of human plague reported annually. After inoculation by a flea bite, Y. pestis multiplies in the lymph nodes and finally overwhelms its rodent or human host with massive growth. The closely related food-borne pathogens Yersinia pseudotuberculosis and Yersinia enterocolitica penetrate into the tissues of their host by crossing the intestinal barrier at the lymphoid follicles called Peyer's patches and then multiply in the abdominal lymphoid tissues.
Pathogenic Yersinia species share the Yop virulon, encoded on a 70-kb plasmid, which is the core of the Yersinia pathogenicity machinery designed for close combat with cells of the immune system (). The Yop virulon comprises both the Yop effector proteins and the proteins necessary for injecting them into host cells. The injected Yops perturb the dynamics of the cytoskeleton, disrupting phagocytosis, and block the production of proinflammatory cytokines, thus favoring the survival of the invading Yersinia.
Figure 1. Secretion of Yops by the Ysc injectisome and translocation across the target cell membrane. When Yersinia are placed at 37°C in a rich environment, the Ysc injectisome is installed and a stock of Yop proteins is synthesized. During their intrabacterial (more ...)
The Yop virulon is an archetype of the type III secretion systems (TTSSs)*
now identified in more than a dozen major animal or plant pathogens (Cornelis and Van Gijsegem, 2000
; Buttner and Bonas, 2002
). Some of these, including Salmonella enterica
, have two TTSSs, both of which are essential for pathogenicity and come into play at different stages of infection. One is required for the initial interaction of S. enterica
with intestinal epithelial cells, whereas the other is expressed only after S. enterica
has gained access to host cells and is required for systemic infection (Galan, 2001
). A homologue of the first S. enterica
TTSS is found in Shigella flexneri
where it also functions to promote invasion of epithelial cells (Sansonetti, 2001
). In enteropathogenic Escherichia coli
, a different TTSS remodels the cytoskeleton of enterocytes, leading to the formation of a pedestal of unknown function underneath the bacterium (Celli et al., 2000
In this mini-review, I will consider the Yop virulon as a model of type III secretion but will draw on other examples when their molecular description has gone beyond that of Yersenia. The virulon consists of three basic components: the Ysc injectisome, spanning the bacterial membranes, the Yop effectors, and the Yop translocators, needed to deliver the effectors across the eukaryotic plasma membrane.