The sequence of the entire genome of the bacillus causing leprosy has been determined in a collaborative effort between Stewart Cole's team at Institut Pasteur and the Sanger Centre in the Great Britain. As Stewart Cole will explain at the international meeting 'Genomes 2000' currently being held at Institut Pasteur, comparison of this sequence with that of the genome of the tuberculosis bacillus (entirely sequenced by the same two teams in 1998) will give valuable information about the two diseases. According to the WHO, there are more than 800 000 new cases of leprosy every year world-wide, and more than 2 million people currently suffer severe disabilities because of this disease.
Leprosy is a chronic infectious disease mostly affecting the skin, peripheral nerves, mucosa membranes of the upper respiratory tract and the eyes. The mutilations it causes result in lepers being rejected in many societies. Ninety-two % of the known cases in the world are in only twelve countries. These most affected countries are: India, Brazil, Indonesia, Myanmar (Burma), Madagascar, Nepal, Ethiopia, Mozambique, Democratic Republic of Congo, Niger, Guinea and Cambodia. In France, about 250 people are treated for leprosy, and there are about 25 new cases a year, mostly in people from countries where the disease is endemic or the DOM-TOMs (Antilles, Guiana, Mayotte).
Sequencing the genome of the leprosy bacillus (Mycobacterium leprae)
was a priority both for research into the disease and for its control. The
collaboration between the Bacterial Molecular Genetics Unit at Institut
Pasteur, directed by Stewart Cole, and the Pathogen Genome Sequencing Unit
at the Sanger Centre (UK), directed by Bart Barrel, started in 1996. This
sequencing project was financed by the Heiser Program for Research in
Leprosy and Tuberculosis of the New York Community Trust, and the Association
Raoul Follereau.
The entire sequence of the genome of the bacillus Mycobacterium leprae
is now available to research scientists. Comparisons with the tuberculosis
bacillus, Mycobacterium tuberculosis, have already started. The genetic
make-up of these two bacilli are very similar: the similarity of some groups
of genes is as high as 93%. However, the M. leprae genome is 3,2
Mb, which is smaller than the 4.4 Mb of M. tuberculosis. The leprosy
bacillus seems to have 'got rid of' non-essential genes. This may explain
its slow growth, which makes culturing the bacillus in the laboratory very
difficult. This in turn greatly hinders research on this bacterium and thus
work on the disease it causes. The comparison of the two genomes may lead
to the identification of growth factors, absent from M. leprae, which
could facilitate research and would be very useful for the production of
vaccines. In contrast, other genes in M. leprae are not found in
M. tuberculosis: these genes may lead to the development of diagnostic
tools for dermatological tests to detect leprosy. Such tools would be valuable
as the earlier the disease is detected, the better the treatment. These
genes only found in M. leprae may also confer particular properties,
for example its neurotropism resulting in the degradation of nerves. The
comparative approach being used is expected to identify new therapeutic
targets and facilitate the rational development of drugs for treating leprosy.
Note that although current chemotherapy is effective, it is both expensive
and extremely impractical as it requires daily administration of a combination
of antibiotics for 6 months (for mild cases) to more than 12 months.
- Stewart Cole, Unité de Génétique moléculaire
bactérienne, Institut Pasteur
Tel: 01 45 68 84 46 - E-Mail: stcole@pasteur.fr
http://www.pasteur.fr/recherche/unites/Lgmb/
- Press office - Institut Pasteur
Tel: 01 45 68 81 46 - E-Mail: presse@pasteur.fr
http://www.pasteur.fr/actu/presse/infos
Source: GENOMES 2000, Conférence Internationale sur les Génomes Microbiens et les Génomes Modèles (International conference on microbial and model genomes), 11-15 April 2000, Institut Pasteur