The complete genome of the leprosy bacillus has been sequenced

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

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 worldwide, 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 percent 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 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 Barrell, 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.

More information

1. The Sanger Centre, which receives the majority of its funding from the Wellcome Trust, is one of the world’s leading genome sequencing centres. Both the Sanger Centre and the Wellcome Trust have been at the forefront of efforts to keep sequence data in the public domain.

   https://www.sanger.ac.uk/
   http://wellcome.org/en/1/biovengensan.html

2. The Wellcome Trust is the world’s largest medical research charity with an annual spend of some £600 million in the current financial year 1999/2000. The Wellcome Trust supports more than 3000 researchers at 300 locations in 30 different countries – laying the foundations for the healthcare advances of the 21st century and helping to maintain the UK’s reputation as one of the world’s leading scientific nations. As well as funding major initiatives in the public understanding of science, the Wellcome Trust is the country’s leading supporter of research into the history of medicine.
3. The DNA of every living organism is made up of four chemical ‘bases’ represented by the letters A, C, G, and T. The bases are paired together, A with T and C with G to produce double-stranded DNA in the familiar helix. The number of base-pairs varies from a few thousand for the smallest viruses to several billions for complex organisms. The DNA sequence of base-pairs contains all the instructions to make an organism: decoding that set of instructions is the heart of a sequencing project.

   The order of the bases (the sequence of DNA) provides the instructions for the functions of the cell. By understanding the order of bases, researchers gain a better understanding of normal and disease processes.