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During Middle Age, the plague decimated almost one third of the European population in less than 3 years. Why is the plague bacillus so pathogenic? Researchers from the Institut Pasteur have discovered that the infection of the ancestral form of the bacillus by a bacterial virus (phage) has been one of the steps that have led to the emergence of such a dreadful organism. For plague specialists, this discovery is a key step towards understanding the pathogenic mechanisms specific to the plague bacillus, and, eventually, towards the development of effective methods for combating the disease.
The plague is far from being eradicated. It continues to rage in various countries, mainly in Africa and Asia. The number of cases is even on the rise in some regions of the world, making it a "re-emerging" disease. Conducting research on the plague is therefore an essential step towards combating this public health threat.
The extraordinary virulence of Yersinia pestis, the causative agent of the plague, has been intriguing researchers for many years. In 2004, a comparison of the Yersinia pestis genome with that of its ancestor, Yersinia pseudotuberculosis (a very similar bacteria but much less pathogenic), was carried out by Elisabeth Carniel, head of the Yersinia unit, and her team at the Institut Pasteur, in collaboration with an American group (1). A number of regions specific to the plague bacillus were identified.
By studying these specific regions, the Pasteur researchers discovered that one of them encodes a filamentous virus (a "bacteriophage"). Bearing in mind that filamentous phages are implicated in the pathogenicity of some other microorganisms, such as the cholera agent, they focused their study on this phage that they named "Ypf " (for Y. pestis filamentous phage).
Using electronic microscopy, they first observed the production by Y. pestis of long phage filaments (see photo) and demonstrated that these particles could infect other bacteria that do not host the phage. The researchers dated the infection of Y. pestis by Ypf back to over 7500 years ago. The maintenance of this mobile element within the bacterial genome suggests that it has provided selective advantages to its host bacterium.
Tests conducted on infected fleas demonstrated that the phage does not play a role in the vector-borne transmission of Y. pestis. However, the researchers found that the phage plays a role in the pathogenicity of the plague bacillus.
How did the infection by Ypf generate a bacterium with a higher pathogenic potential? The Institut Pasteur team is now trying to elucidate this question. Understanding these mechanisms could open up new avenues for developing more efficient means of combating the plague.
Moreover, as outlined by the authors, "since this phage has the capacity of being secreted by its bacterial host and infecting new bacterial cells, it has the potential of being transferred horizontally, leading to the emergence of new pathogens."
Yet another reason for gaining a clear understanding of Ypf ...
The filamentous phage produced by Yersinia pestis, the plague agent (false-colour electron microscopy)
(1) Read our press release dated September 20, 2004
(2) "A horizontally acquired filamentous phage contributes to the pathogenicity of the plague bacillus": Molecular Microbiology, February 2007.
Anne Derbise (1), Viviane Chenal-Francisque (1), Flavie Pouillot (1), Corinne Fayolle (1), Marie-Christine Prévost (2), Claudine Médigue (3), Bernard Joseph Hinnebusch (4) and Elisabeth Carniel (1)
1. Yersinia Unit, Institut Pasteur, Paris
2. Electron Microscopy Platform, Institut Pasteur, Paris
3. Genoscope, CNRS-UMR 8030, Comparative Genomic Workshop (Atelier de Génomique Comparative), Evry
4. Laboratory of zoonotic pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, USA
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