A global team of scientists, including researchers from the Yale School of Public Health, has created the first cross-species genomic comparison of the 20 species of Leptospira, a bacterial genus that infects as many as 10 million people annually.
By comparing the complete genome sequences of all known species of Leptospira the researchers discovered which genes make this bacterium pathogenic. The finding could lead to better treatment for leptospirosis, including improved diagnosis and a possible vaccine for a disease that kills an estimated 59,000 people annually.
Humans are exposed to leptospirosis through direct contact with water or soil contaminated by the urine of infected animals, such as rats. Symptoms range from aches and mild fever to severe damage of the liver, kidney or central nervous system. The disease is pronounced throughout the developing world and people living in crowded urban areas, such as Brazil’s favelas, are particularly susceptible.
“This work is of broad importance,” said Dr. Joseph Vinetz, a visiting professor at the School of Public Health and the director of the UC San Diego Center for Tropical Medicine. “It will provide a roadmap for all future research.”
The findings are published online in the journal PLoS Neglected Tropical Diseases.
The collaborative effort by 29 scientists contributes to a much-improved understanding of Leptospira’s evolutionary history. Of the known species of Leptospira, nine are pathogenic, six non-pathogenic and five where the role of virulence is unclear. Earlier work had analyzed available genomes of only a few Leptospira, but the analyses were not broad enough to draw general conclusions. The latest work allowed a direct comparison of infectious and non-infectious genomes and of highly pathogenic and intermediately pathogenic Leptospira.
“Leptospirosis is the most important infectious disease transmitted from animals to people,” said Dr. Elsio Wunder, associate research scientist in the lab of Professor Albert Ko at the Yale School of Public Health. The finding will also open up other areas of research, including experimental approaches to understanding mechanisms of disease pathogenesis and how Leptospira persist in the environment, both of which are critical for developing new interventions to reduce the disease’s global impact.
While some species of Leptospira are non-infectious, getting nourishment from dead or decaying organic matter, other species are infectious, with the bacterium colonizing the kidneys, for example, of mice and rats but not producing disease symptoms. In livestock and domesticated animals, Leptospira can cause acute kidney, liver and lung damage and result in fetal loss.
Researchers at University of California, San Diego and J. Craig Venter Institute planned the scope of the project. Yale School of Public Health scientists took the lead in international efforts to understand the global burden of leptospirosis, and researchers from around the world, including Brazil, France, Netherlands, Australia, Thailand, and Uruguay, contributed to the research.