July 13, 2007
Leptospirosis: the first virulence gene identified
Although leptospirosis is one of the so-called "neglected" diseases, it still causes some 500,000 severe cases in humans around the world each year and also comprises a veterinary problem. A century after the pathogenic agent that causes the disease was found, researchers at the Institut Pasteur have discovered a gene that is essential to the bacteria's virulence. Their work, published in PLoS Pathogens, opens the door for the application of new diagnostics and vaccines.
Leptospirosis, a zoonosis that is found throughout the world, is caused by a bacteria from the Leptospira interrogans complex. Its principal reservoirs are rodents, especially rats, which excrete the bacteria in their urine. The leptospires survive in freshwater and in muddy soil, which facilitates contamination. Humans and other animals, such as livestock or companion animals such as dogs, are infected via breaks in their skin or through their mucus membranes. In humans the manifestations of the disease vary considerably (from flu-like symptoms to hemorrhagic symptoms that affect multiple organs) and can be severe: it causes renal failure that leads to death in 5 to 20% of cases. It affects some 300 people in France each year and is responsible for 500,000 severe cases around the world annually, especially in Latin America and Southeast Asia.
Work carried out by Mathieu Picardeau from the Spirochetes Biology Unit of the Institut Pasteur in collaboration with a team from Brazil's Fondation Oswaldo Cruz resulted in the identification for the first time of a virulence gene that is essential to this bacteria. This find took place a century after the discovery in 1907 by the American Arthur M. Stinson of the germ that causes this disease.
The researchers were able to identify this essential virulence element, named loa22 , through random mutagenesis technique: the mutants in which this gene is inactive lose their ability to infect. The reintroduction of loa22 into these mutants restores their pathogenic ability. The gene loa22 encodes a protein in the bacteria's external membrane.
Mathieu Picardeau underlines that "Our goal now is to verify whether this protein can be used to carry out diagnostic tests and to make more effective vaccines".
The diagnostic tests that are currently in use, which are based on serology, take several weeks in practice. A symptomatic diagnosis of the disease is difficult to establish, so a quick test will be useful for carrying out appropriate treatment. As for vaccination programs, those that are currently in use (they are used in France in persons at risk, such as sewer workers, slaughterhouse workers, and the like) have only limited efficacy. Therefore, more effective vaccines are also desired.
The researchers from the Institut Pasteur are therefore already exploring this new avenue, which may allow a more effective fight against leptospirosis, considered to be the most widespread zoonosis in the world and a cause of major economical losses in the livestock industry due to concerns over human sanitation.
Bactéria Leptospira (false-color electron microscopy) © M. Picardeau/E. Couture-Tosi /Institut Pasteur
Paula Ristow (1), Pascale Bourhy (1), Flàvia Weykamp da Cruz McBride (2), Claudio Pereira Figueira (2), Michel Huerre (3), Patrick Ave (3), Isabelle Saint Girons (1), Albert I. Ko (2,4) et Mathieu Picardeau (1)
1. Spirochetes Biology Unit, Institut Pasteur, Paris;
2. Centro de Psquisas Gonçalo Moniz, Fondation Oswaldo Cruz, Salvador, Brazil;
3. Histotechnology and Pathology Expert Research Unit, Institut Pasteur, Paris;
4. International Medicine and Infectious Disease Division, Weill Medical College of Cornell University, United States
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