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YadA, the multifaceted Yersinia adhesin
1Institute of Biomedicine, Department of Medical Biochemistry, University of Turku, Finland.
Abstract:
The adhesion protein YadA is encoded by the yadA gene located in the 70-kb virulence plasmid of Yersinia (pYV) that is common to the pathogenic Yersinia species (Y. pestis, Y. pseudotuberculosis and Y. enterocolitica). YadA is a virulence factor of Y. enterocolitica, however, YadA seems to be dispensable for the virulence of Y. pseudotuberculosis, and in wild-type Y. pestis the yadA gene has a frameshift mutation silencing the gene. Expression of the Y. pseudotuberculosis YadA in Y. pestis reduces its virulence. YadA is a homotrimer of ca. 45-kDa subunits that are anchored to the outer membrane via their C-termini, while their N-termini form a globular head on top of a stalk; the 'lollipop'-shaped YadA structure covers the entire bacterial surface giving it hydrophobic properties. The yadA gene expression is induced at 37 degrees C by the temperature-dependent transcriptional activator LcrF. YadA is a multifaceted protein as revealed by its different biological properties. YadA+ bacteria bind to collagens, laminin, fibronectin, intestinal submucosa, mucus, and to hydrophobic surfaces like polystyrene. YadA+ bacteria autoagglutinate in stationary culture and also specifically agglutinate guinea pig red blood cells. YadA is also a potent serum resistance factor as it inhibits the classical pathway of complement. As invasin, it mediates low rate invasion to tissue culture cells. In a rat model of reactive arthritis YadA and specifically YadA-mediated collagen binding is necessary for Y. enterocolitica to induce the disease. Despite of this wealth of information or perhaps because of it, the in vivo role of YadA during infection remains still largely unresolved.
Insights
The YadA adhesion protein in Yersinia enhances bacterial binding to host tissues and inhibits complement, but its exact role in infection requires further study. This protein is crucial for Yersinia enterocolitica virulence.
Area of Science:
- Microbiology
- Molecular Biology
- Immunology
Background:
- The YadA protein, encoded by the yadA gene on the Yersinia virulence plasmid (pYV), is present in pathogenic Yersinia species.
- While YadA is a virulence factor in Yersinia enterocolitica, its role is less clear in Yersinia pseudotuberculosis and Yersinia pestis, where the gene is often silenced or mutated.
- YadA is a homotrimer anchored to the bacterial outer membrane, forming a 'lollipop' structure that imparts hydrophobic properties and mediates interactions with host components.
Purpose of the Study:
- To investigate the multifaceted biological properties and in vivo role of the YadA adhesion protein during Yersinia infections.
- To understand how YadA contributes to bacterial virulence, host tissue adhesion, serum resistance, and disease induction.
Main Methods:
- Analysis of yadA gene presence and expression across different Yersinia species.
- Characterization of YadA structure and its interaction with host substrates like collagens, laminin, and fibronectin.
- Assessment of YadA's role in bacterial autoagglutination, red blood cell agglutination, serum resistance, and invasion of tissue culture cells.
- Evaluation of YadA's necessity in a rat model of reactive arthritis.
Main Results:
- YadA mediates binding to various host extracellular matrix components and hydrophobic surfaces.
- YadA+ Yersinia exhibits autoagglutination, specific red blood cell agglutination, and resistance to complement-mediated serum killing.
- YadA is essential for Yersinia enterocolitica to induce reactive arthritis in a rat model, particularly through collagen binding.
- Expression of Y. pseudotuberculosis YadA in Y. pestis reduced its virulence.
Conclusions:
- YadA is a crucial virulence factor for Yersinia enterocolitica, mediating adhesion, serum resistance, and disease pathogenesis.
- Despite its characterized functions, the precise in vivo significance of YadA across all pathogenic Yersinia species remains largely unresolved.
- Further research is needed to fully elucidate the complex in vivo roles of YadA during infection.