February 27, 2007
Aquatic Predator Insect Saliva May Protect Against Buruli Ulcer
Buruli ulcer is a necrotizing skin disease that is very disabling, caused by bacteria that inhabit aquatic environment. It is rife in several regions of the world and is developing at a disturbing rate in West Africa. Researchers at the Institut Pasteur and Inserm, working together with university and institute teams from the Institut Pasteur International Network, recently proved that the immunogenic properties of the saliva of aquatic predator insects, which are hosts and vectors of the bacillus named Mycobacterium ulcerans, offer protection against the development of lesions caused by this species of Mycobacterium ('PLoS Medicine'). This work has opened the door to new possibilities for researching new preventive strategies.
Buruli ulcer was declared an emerging disease by the WHO in 1998. Caused by an environmental mycobacteria known as Mycobacterium ulcerans, over the past few years this disease has become the third most widespread mycobacteriosis after tuberculosis and leprosy. It is rife in humid tropical regions and manifests initially in the form of a nodule, developing later into vast skin ulcerations -that can be reproduced in experimental animals by the injection of a toxin secreted by M. ulcerans- . Left untreated, afflicted individuals develop serious disabilities, such as significant limitations in joint movements and disfiguring scars, among others.
It has been established that there is no person-to-person transmission of the bacillus, and that people are contaminated through contact with an aquatic environment. The increase in the number of cases and the emergence of new disease foci are caused by ecological disturbances (such as deforestation, aquatic farming, artificial lakes and irrigation), which probably promote the growth of aquatic insect populations. After establishing, in 2002, that aquatic predator insects might host the bacillus in their salivary glands and transmit it to people through accidental bites (1), Laurent Marsollier (Institut Pasteur Bacterial Molecular Genetics Unit and the Université d’Angers), in cooperation with other teams from the Institut Pasteur in Paris, Inserm Unit 601, "Research in Cancerology", in Nantes, an Avenir Inserm team at the Institut Pasteur of Korea and the Centre Pasteur of Cameroon, in particular (2), have just proven that exposure to repeated bites by these same insects that are not carriers of M. ulcerans, can offer protection against the development of the lesions caused by the bacteria.
Researchers began with observations in the field, which showed that people who were most exposed to insect bites were the least afflicted by the disease. Based on this observation, they issued the hypothesis that regular bites from healthy insects could offer protection that would result in the absence of lesions at sites on the skin where the bacillus and the insect saliva were co-inoculated. Work performed with laboratory mice indicates that this hypothesis is plausible. Indeed, in mice previously immunized with salivary gland extracts or exposed to bites from healthy insects, the development of skin lesions is unusual. In order to support their experimental results, the researchers conducted a serological analysis in the Buruli ulcer endemic region. This study established that subjects with M. ulcerans lesions had insect saliva -binding antibody levels that were lower than those of Buruli ulcer- free individuals exposed to bites from these insects.
"Therefore, it would seem that aquatic insect saliva contains molecules that can offer a protective effect", concludes Laurent Marsollier. "Our objective is now to research them."
These studies will be pursued through a transversal research program* that was recently launched by Institut Pasteur. Its mission, in addition to developing vaccine strategies for which this study has opened prime avenues, is to develop an early diagnostic test that can be used in the field, and to identify inhibitors to the synthesis of the M. ulcerans toxin, which would lead to the development of treatment drugs.
*This program includes teams from the Institut Pasteur in Paris, the Institut Pasteur in Korea, the Centre Pasteur in Cameroon, the Institut Pasteur in Brussels and the University Hospital Centres of the Universities Angers-Nantes.
This study has received support from the Fondation Raoul Follereau.
(1) : Marsollier L, Robert R, Aubry J, Saint Andre JP, Kouakou H, et al. (2002) Aquatic insects as a vector for Mycobacterium ulcerans. Appl Environ Microbiol 68: 4623-4628.
(2) "Protection against Mycobacterium ulcerans lesion development by exposure to aquatic insect saliva": PLoS Medicine, 27 February 2007.
Laurent Marsollier (1,2), Estelle Deniaux (2), Priscille Brodin (3), Agnès Marot (2), Christelle Mjondji Wondje (4), Jean-Paul Saint-André (2), Annick Chauty (5), Christian Johnson (6), Fredj Tekaia (7), Edouard Yeramian (8), Pierre Legras (2,9), Bernard Carbonnelle (2), Gilles Reysset (1), Sara Eyangoh (4), Geneviève Milon (10), Stewart T. Cole (1), Jacques Aubry (11)
1.Bacterial Molecular Genetics Unit, Institut Pasteur, Paris, France, 2. Study Group on Pathogenic Host Interactions, University Hospital Center and School of Pharmacy of Angers Angers, France, 3. Avenir Inserm Team, Institut Pasteur of Korea, Seoul, South Korea 4. Mycobacteria Laboratory, Centre Pasteur of Cameroon, Yaounde, Cameroon 5. Buruli Ulcer Diagnosis and Treatment Center, Pobe, Benin 6. National Buruli Ulcer Program, Ministry of Public Health, Cotonou, Benin 7. Molecular Genetics of Yeast Unit Institut Pasteur, Paris, France, 8. Structural Bio-Computing Unit Institut Pasteur, Paris, France, 9. University Hospital Animal House, Angers, France, 10. Immunophysiology and Intracellular Parasitism Unit Institut Pasteur, Paris, France, 11. Inserm U601, Université de Nantes, School of Pharmacy Nantes, France