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Molecular determinants of Yersinia pathogenesis
1Microbial Pathogenesis Unit, International Institute of Cellular and Molecular Pathology (ICP), Brussels, Belgium.
Abstract:
The genus Yersinia contains three pathogenic species: Yersinia pestis, Y. pseudotuberculosis and Y. enterocolitica. Even though the three species use different routes to infect their host and provoke diseases of different intensity, they share a common tropism for the lymphoid tissue and they are able to resist the primary immune response of the host. The main genetic determinants involved in this resistance are encoded by a highly conserved 70-kb virulence plasmid. The genes harbored by the pYV plasmid encode the lipoprotein YlpA, the outer membrane protein YadA, and a group of at least 11 secreted proteins called Yops. The pYV plasmid also encodes the apparatus necessary for the secretion of the Yop proteins, as well as those involved in the regulation of Yop synthesis. The Yop proteins are secreted by a specific secretion system which is considered as the archetype of a new secretion pathway called type III. After their secretion they are immediately internalized into the cytosol of a target eukaryotic cell, which represents a new phenomenon in microbial pathogenesis. The chromosome of Y. enterocolitica completes the virulence panoply of the bacteria by encoding an enterotoxin called Yst, fibrillae named Myf and an invasin called Inv.
Insights
Pathogenic Yersinia species resist host immunity using a virulence plasmid (pYV) encoding Yops. These Yop proteins are secreted via a type III secretion system and directly enter host cells, aiding bacterial pathogenesis.
Area of Science:
- Microbiology
- Molecular Biology
- Immunology
Background:
- The genus Yersinia comprises three pathogenic species: Yersinia pestis, Y. pseudotuberculosis, and Y. enterocolitica.
- These species share tropism for lymphoid tissues and resist host immune responses.
- Virulence is largely mediated by a conserved 70-kb virulence plasmid (pYV).
Purpose of the Study:
- To elucidate the genetic determinants of Yersinia virulence, focusing on the pYV plasmid.
- To describe the role of Yop proteins and their secretion system in pathogenesis.
- To identify additional virulence factors encoded on the Y. enterocolitica chromosome.
Main Methods:
- Analysis of genes encoded by the pYV virulence plasmid.
- Characterization of Yop proteins, including their secretion and internalization mechanisms.
- Identification of chromosomal virulence factors in Y. enterocolitica, such as enterotoxin (Yst), fibrillae (Myf), and invasin (Inv).
Main Results:
- The pYV plasmid encodes key virulence factors: YlpA, YadA, and at least 11 Yop proteins.
- A type III secretion system, encoded by pYV, is responsible for Yop secretion.
- Yop proteins are directly translocated into the host cell cytosol, a novel pathogenic mechanism.
Conclusions:
- The pYV plasmid is crucial for Yersinia's ability to resist host immunity and establish infection.
- Type III secretion of Yops represents a significant virulence strategy in Yersinia pathogenesis.
- Chromosomal factors like Yst, Myf, and Inv further contribute to the virulence of Y. enterocolitica.