September 20, 2004
New possibilities for fighting the plague
The plague, one of the most dangerous bacterial diseases for man, is currently reemerging in the world. Comparative genome work coordinated by researchers at Institut Pasteur and at Lawrence Livermore National Laboratory in the US, has shed light on the genetic bases that accompanied the emergence of the extremely virulent plague bacillus from a much less pathogenic ancestor, less than 20,000 years ago. These results, published in PNAS, also made it possible to identify specific genes of the plague bacillus that are choice targets for the future development of new diagnostics, treatments and vaccines against this blight.
With nearly 30,000 human cases declared over a period of about ten years, the plague is far from being a disease of the past, and is even currently reemerging in the world. Focuses still remain, not only in Africa, Asia and South America, but also in the United States, where a dozen human cases are reported each year on average. Concern related to this terrible disease has been heightened by the appearance of a strain with multiple resistance to antibiotics, discovered in 1995 by researchers at Institut Pasteur. The plague bacillus is also categorized among the most potentially dangerous agents of bioterrorism.
In 1999, the team led by Elisabeth Carniel at the Institut Pasteur, working in cooperation with the group led by Mark Achtman at the Max-Planck-Institut in Berlin, showed that the plague bacillus, Yersinia pestis, is a very recent descendant of Yersinia pseudotuberculosis, a much less virulent bacteria that causes gastrointestinal disorders.**
In collaboration with the group led by Emilio Garcia of Lawrence Livermore National Laboratory in the United States, Elisabeth Carniel’s team thus launched a sequencing program for the Yersinia pseudotuberculosis genome. The analysis of this genome, conducted by a consortium of French and American teams, and its comparison with that of Yersinia pestis, has made it possible to update a certain number of genes and metabolic processes that have diverged between the two species and that are potentially involved in the extreme virulence of the plague bacillus.
The researchers have thus discovered six chromosomal regions in Yersinia pestis that have been acquired by the bacillus when it diverged from Y. pseudotuberculosis, and have discovered the existence of many genes (representing over 13% of the genome studied) that were deactivated when it emerged less than 20,000 years ago. These modifications have resulted in the birth of one of the most feared pathogens in human history.
Researchers are now characterizing the genetic modifications at the root of the appearance of Yersinia pestis that might explain its exceptional virulence and its very particular clinical and epidemiological characteristics.
Aside from the fundamental knowledge that this study offers in terms of understanding the emergence of new diseases, it also creates possibilities for identifying new diagnostic, therapeutic and vaccination targets in order to more effectively fight the plague.
* This work has been subsidized by the U. S. Department of Energy (for the LLNL) and by the Délégation Générale à l'Armement [French General Armament Delagation] (for Institut Pasteur).
P. S. G. Chain (1), E. Carniel (2), F. W. Larimer (3), J. Lamerdin (1), P. O. Stoutland (1), W. M Régala (1), A. M. Georgescu (1), L. M. Vergez (1), M. L. Land (3), V. L. Motin (1), R. R. Brubaker (4), J. Fowler (4), J. Hinnebusch (5), M. Marceau (6), C. Medigue (7), M. Simonet (6), V. Chenal-Francisque (2), B. Souza (1), D. Dacheux (2), J. M. Elliott (1), A. Derbise (2), L. J. Hauser (3), and E. Garcia (1)
(1) Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, USA ; (2) Unité de Recherche Yersinia, Institut Pasteur ; (3) Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, USA ; (4) Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, USA ; (5) Rocky Mountain Laboratories, Hamilton, USA ; (6) Institut National de la Santé et de la Recherche Médicale E0364, Université de Lille2 Institut Pasteur de Lille ; (7) Genoscope/Centre National de la Recherche Scientifique-Unité Mixte de Recherche 8030, 91006 Evry
*Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis" PNAS. Novembre 1999.
Mark Achtman (1), Kerstin Zurth (1), Giovanna Morelli (1), Gabriela Torrea (2), Annie Guiyoule (2), and Elisabeth Carniel (2),
(1) Max-Planck-Institut für molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; (2) Unité de Bactériologie Moléculaire et Médicale, Laboratoire des Yersinia, Institut Pasteur, 75724 Paris Cedex 15, France
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