From skeletons and biopsies, an international team of scientists was successful in reconstructing a dozen medieval and modern genomes of the leprosy-causing bacteria Mycobacterium leprae. Under the direction of Professor Johannes Krause, University of T-bingen, and Professor Stewart Cole, Swiss Federal Institute of Technology of Lausanne (EPFL), the research group created a genome from archaeological finds for the first time without having to resort to a reference sequence. Professor Almut Nebel and Dr. Ben Krause-Kyora, both of the Institute of Clinical Molecular Biology, Kiel University, belong to the team, whose findings are to be published this week in Science magazine.
Leprosy, a devastating infectious and chronic disease, was widespread in Europe until the Late Middle Ages. Persons infected with the disease were isolated in leprosy colonies specifically built for the patients. Today, the disease is found in 91 countries worldwide with more than 200,000 new infections per year. In order to trace the history of the disease, the scientists reconstructed the complete genomes of M. leprae from five medieval skeletons from Denmark, Sweden and Great Britain. These specimens exhibited the characteristic bone changes associated with leprosy. Additionally, the M. leprae genetic substance was decoded from seven biopsy samples of contemporary patients.
The researchers compared the European medieval M. leprae genome with those of the seven biopsies and four additional modern bacteria strains. They observed that all M. leprae strains have a common ancestor that existed less than 4000 years ago. This result is supported by the earliest archaeological evidence of the disease in India. The genome-wide comparisons suggest unusually minor changes of the bacteria's genetic material within the last 1000 years, which presumably had no effects on the virulence of the pathogen. This evidence suggests that the end of the leprosy epidemic was influenced by other factors such as improved social conditions during the Middle Ages. The research team also demonstrated that a form of M. leprae, which existed in Europe during the Middle Ages, can currently be observed in the Middle East. Another medieval strain from Europe has striking similarities to bacteria that are currently identified in armadillos and leprosy patients in North America, pointing to a European origin of the disease in America.
Surprisingly, a much larger amount of pathogen DNA was observed in the examined skeletons than is usually found in contemporary patients. The researchers ascribe this phenomenon to the circumstance that the bacterial DNA probably decomposes very slowly as a result of the extremely thick cell wall of the leprosy bacterium, thus enabling its accumulation in the skeletons over time. "This makes it possible that certain forms of bacterial DNA remain preserved above the maximal age for mammalian DNA, which is approximately one million years", stated Johannes Krause. "Thus, it should be possible to trace the disease back to its prehistoric origins."
"The DNA of the pathogen was particularly well-preserved in a skeleton from Denmark, although the disease was not strongly pronounced in the ca. 25-year-old woman", commented Almut Nebel. This DNA sample enabled the assembly of an ancient pathogen from scratch for the first time without comparison to a reference sequence. "We have contacted the Danish colleagues who provided us with the important skeletons for the investigation. The DNA was extracted from the teeth of the lepers and subsequently subjected to a first molecular feasibility test", mentioned Ben Krause-Kyora. Moreover, the researchers in Kiel repeated the investigations of their colleagues from T-bingen in order to independently demonstrate the exceptional results. The research project in Kiel was supported by the Graduate School Human Development in Landscapes and the Cluster of Excellence `Inflammation at Interfaces-.
Metagenomic sequencing improves detection of rare pathogens in CNS infections