From East Asia into the world: New study on the global spread of multidrug resistant Tuberculosis pathogens

January 19, 2015
An international group of scientists led by the Research Center Borstel and the German Center for Infection Research (DZIF), the Institut Pasteur de Lille and the Muséum National d’Histoire Naturelle in Paris unraveled for the first time the global spread of multidrug resistant (MDR) Mycobacterium tuberculosis (Mtb) strains of the so-called Beijing lineage. The study shows that efficient tuberculosis (TB) surveillance based on molecular methods is essential to detect outbreaks of MDR-TB strains and to contain the global emergence of MDR-TB.

The diagnosis of multidrug resistant (MDR) tuberculosis is followed by a prolonged antituberculous therapy with severe side effects for many patients. Researchers now identified a specific subpopulation of tuberculosis bacilli associated with increasing numbers of MDR tuberculosis patients since the 1990s primarily in countries of the former Soviet Union. The picture is showing a clinician from Chisinau, Moldova during X-ray diagnostic. (Picture from Prof. Christoph Lange, Research Center Borstel)

How do pathogens spread? Which factors are important? Why are some strains more successful than others? An international consortium of 55 scientists guided by Prof. Stefan Niemann (Research Center Borstel, German Center for Infection Research, DZIF) and his French colleagues Prof. Philip Supply (Institute Pasteur de Lille) and Prof. Thierry Wirth (Muséum National d'Histoire Naturelle, Paris) addressed these questions and investigated the evolution and geographical distribution of tubercle bacilli of the so-called Beijing lineage. Mtb strains of this subtype have been mainly found in Eastern Europe and Central Asia, regions in the world where MDR-TB rates reach their maximum.
The researchers analyzed the DNA fingerprints of nearly 5,000 clinical Mtb Beijing strains from 99 countries to define the global population structure of the Beijing lineage and detect the global spread of particular subtypes. In addition, the genome sequence of 110 strains was determined to define changes in the genetic make-up potentially contributing to an enhanced fitness of MDR strains. The results of this study have been published in the renowned journal Nature Genetics. “We could demonstrate, that the origin of the Beijing lineage is in East Asia and that it has spread across the globe in different waves triggered by human migration events” says Prof. Niemann, coordinator of the study at the Research Center Borstel and head of the DZIF priority area “tuberculosis”. One major finding of the study was that the high MDR-TB rates in Eastern Europe are mainly due to the massive transmission of two Beijing MDR outbreak strains. Particular beneficial genome variants are presumable the reason for their efficient transmission and the extreme expansion over the last 20 years. “Interestingly, we could date the start of the MDR TB epidemic to the time of the breakdown of the public health system in the former Soviet Union” explains Dr. Matthias Merker, first author of the paper and points to another important factor for the global control of the MDR-TB epidemic.
The uncontrolled transmission of MDR Mtb strains in Eastern Europe and other regions of the world such as South Africa represents a tremendous challenge for TB control in the 21th century. The current study demonstrates that efficient TB surveillance based on molecular methods is essential to detect and contain outbreaks of highly virulent MDR strains. In addition, the rapid resistance detection to guide effective treatment and the development of new antituberculous drugs are key to fight TB successfully in future. “These topics are key questions in the tuberculosis unit of the DZIF and the EU FP7 Patho-Ngen-Trace project. Here, the translation of the basic research results into application is of particular importance” explains Prof. Niemann.

Merker et al: Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nature Genetics, Advance Online Publication on 19 January 2015, doi: 10.1038/ng.3195


Prof. Stefan Niemann
Forschungszentrum Borstel – Leibniz-Zentrum für Medizin und Biowissenschaften
Parkallee 1
23845 Borstel
Telefon: 04537/188 7620