A French genetics study comparing strains of leprosy-causing bacteria has revealed some surprises about how the pathogen evolved and how it was spread across the continents by human migrations. The research, led by scientists at the Pasteur Institute in Paris, appears in the 13 May issue of the journal Science, published by AAAS, the nonprofit science society.
The findings indicate that the world's existing leprosy infections are all caused by a single bacterial clone that has spread yet barely mutated for centuries. They also show that the disease may have begun in East Africa, as opposed to India as previously thought, and then spread to the other continents in part through European colonialism and later the slave trade.
One of the oldest known human diseases, leprosy is still a significant problem in parts of the developing world, especially India. According to the World Health Organization, roughly 500,000 new cases were detected in 2003. (who.int/lep/stat2002/global02.htm)
"Leprosy is still very real and devastating to patients who aren't treated appropriately. The better we can understand this pathogen's genome and the subtle differences among its various strains worldwide, the better position we'll be in to ultimately eliminate the disease," said Caroline Ash, Senior Editor at Science.
The ability to trace an infection back to a certain region may help public health workers monitor the movement of the disease over time and determine the geographic source of new infections, said study author Stewart Cole of the Pasteur Institute.
Historically, it's been thought that leprosy originated in the Indian subcontinent and was then introduced to Europe by Greek soldiers returning from the Indian campaign of Alexander the Great, according to Cole. More research will be necessary to confirm this, but the new findings indicate that the disease actually originated in East Africa or perhaps the Near East, then migrated eastward and westward.
Europeans and North Africans then spread Leprosy to West Africa, and the slave trade brought the disease from West Africa to the Caribbean and South America, the study suggests. Europeans also introduced leprosy to North America.
"Colonialism was extremely bad for parts of the world in terms of human health," said Cole.
The disease, caused by Mycobacterium leprae, primarily affects the skin and nervous system, particularly the limbs and digits. It's not especially contagious, as people once widely believed, but it can cause permanent disability and disfigurement and is still a source of social stigma. The disease is treatable with a combination of antibiotics.
The bacterium has long puzzled researchers because its genome is filled with an unusually high proportion of damaged, nonfunctional genes. This is probably why it grows exceedingly slowly, making it difficult for researchers to study because they can't grow it in culture. In fact, M. leprae only lives in humans and in armadillos (which might have acquired the bacterium by eating infected human cadavers), and it can also grow in the footpads of mice.
Cole and his international research team compared the genomes of seven strains of M. leprae taken from patients around the world and then grown in armadillos until the samples were large enough to analyze. They focused on genetic sequences known to be dynamic -- to move around, copy themselves or disappear -- and thus most likely to reflect evolutionary change, but found strikingly little variation.
Next, the researchers looked for mutations known as "single nucleotide polymorphisms" or "SNPs," which are substitutions of single nucleotides or "letters" at a specific spot in the genome. They found only three spots where useful SNPs occurred.
"Finding so few SNPs is pretty unusual. It's the least number of SNPs I'm aware of in any bacterium," Cole said.
At each of the three SNP locations, one of four different nucleotides can be substituted, making for a possible 64 different combinations in the genetic sequence. In a study of 175 different bacteria samples from 21 countries, the researchers found only four of these possible combinations.
Overall, the genetic similarity between the different samples suggests that the bacterium's genome is exceedingly stable.
"It seems that there was only a single source of the bacterium that was at the origin of this global pandemic," Cole said.
Each of the four SNP combinations was most common in a certain geographic region, allowing the researchers to trace how the pathogen had spread from its original source.
Additional contacts: French: Michaela Jarvis, AAAS, 1-925-945-8229 PST, michaelajarvis@sbcglobal.net
Corinne Jamma, Pasteur Institute, 33-1-40-61-33-41, cjamma@pasteur.fr
English: Kathy Wren, AAAS, 1-617-628-0373 EST, kwren@aaas.org
Cole's coauthors are Marc Monot, Nadine Honoré, Thierry Garnier, Romulo Araoz, Jean-Yves Coppée and Céline Lacroix of the Pasteur Institute in Paris, France; Samba Sow at Centre National d'Appui à la lutte Contre la Maladie in Bamako, Mali; John S. Spencer and Patrick J. Brennan at Colorado State University in Fort Collins, CO, USA; Richard W. Truman and Diana L. Williams at Louisiana State University in Baton Rouge, LA, USA; Robert Gelber at Leonard Wood Memorial Center for Leprosy Research in Cebu, Philippines; Marcos Virmond at Instituto "Lauro de Souza Lima" in São Paulo, Brazil; Béatrice Flageul at Hôpital Saint-Louis in Paris, France; Sang-Nae Cho at Yonsei University College of Medicine in Seoul, Republic of Korea; Baohong Ji at Faculté de Médecine Pitié-Salpêtrière in Paris, France; Alberto Paniz-Mondolfi and Jacinto Convit at Instituto de Biomedicina in Caracas, Venezuela; Saroj Young and Paul E. Fine at London School of Hygiene and Tropical Medicine in London, UK; and Voahangy Rasolofo at Institute Pasteur de Madagascar in Antananarivo, Madagascar.
The study was funded by the Pasteur Institute, the Association Française Raoul Follereau, Lepra, the Consortium National de Recherche en Génomique, and the National Institute of Allergy and Infectious Diseases.
The American Association for the Advancement of Science (AAAS) is the world's largest general scientific society, and publisher of the journal, Science. AAAS was founded in 1848, and serves some 262 affiliated societies and academies of science, serving 10 million individuals. Science has the largest paid circulation of any peer-reviewed general science journal in the world, with an estimated total readership of one million. The non-profit AAAS is open to all and fulfills its mission to "advance science and serve society" through initiatives in science policy; international programs; science education; and more.
Contact: Jessica Lawrence-Hurt
jlawrenc@aaas.org
1-202-326-7088
American Association for the Advancement of Science
http://www.aaas.org
14 May 2005
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