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Pathogen Page

Yersinia pestis

I. General Information

1. NCBI Taxonomy ID:

2. Disease:

Plague

3. Introduction

The causative agent of plague was identified by the Swiss microbiologist Alexandre Yersin who was investigating an 1894 outbreak in Hong Kong (Perry et al., 1997). This gram-negative bacterium is the etiological agent of plague and exists as three forms of human disease: bubonic, septicemic, and pneumonic. Of these, the pneumonic plague is of most concern as a biological threat because of the rapid onset, high mortality, and rapid spread. Although antibiotics can successfully treat plague, the fatality rate is high when treatment is delayed >24 h after the onset of symptoms (Chiuchiolo et al., 2006).

At present, no plague vaccines are available in the United States. Several vaccines have been developed, including killed whole-cell formulations and the live attenuated EV76 vaccine. Although these vaccines have been used in humans, they offer low levels of protection, have numerous adverse side effects, and require frequent immunizations with consequent prolonged time to develop immunity. A promising subunit vaccine is based on the virulence (V) antigen. V antigen–based DNA vaccines are also being developed. These vaccines elicit low antibody titers, and protection against a Y. pestis challenge is reached only after several immunizations (Chiuchiolo et al., 2006).

4. Microbial Pathogenesis

The core of the Yersinia pestis pathogenicity machinery is the Yop virulon, encoded on the 70-kb plasmid of pathogenic Yersinia species. The Yop virulon consists of three basic components: the Ysc injectisome (an organelle which spans the bacterial membrane), the Yop effectors, and the Yop translocators that are involved in delivering the effectors across the eukaryotic plasma membrane. Once injected, Yop proteins perturb the dynamics of the cytoskeleton (disrupting phagocytosis) and block the production of proinflammatory cytokines, thus favoring the survival of Yersinia pestis while inducing apoptosis in the macrophage. The Yop virulon is an archetype of the type III secretion system now identified in more than a dozen major animal or plant pathogens (Cornelis, 2002).

Link to pathogenesis of Yersinia pestis in HazARD.

5. Host Ranges and Animal Models

Plague is primarily a zoonotic infection, occurring in urban or wild rodent populations. Rodents that could be characterized as enzootic hosts (i.e., in what rodent populations Yersinia pestis is found naturally) have not been conclusively identified, but certain species of rat, vole, mouse, and gerbil are suspected (Perry et al., 1997).

6. Host Protective Immunity

To clear Yersinia infection, the host must develop a strong adaptive immune response, and IFN-γ-producing CD4 and CD8 T cells are essential in this process (Heesemann et al., 2006). The anti-YresiniaV antigen antibody-mediated neutralization of Yersinia-induced macrophage cytotoxicity correlates with in vivo protection (Bashaw et al., 2007). Humoral antibody response also plays a major role in mediating protection as demonstrated by passive transfer of anti-deF1 DNA antiserum (Grosfeld et al., 2003).

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