MDR Tuberculosis · Evolution and success of the multi-drug resistant M. tuberculosis SIT41 (LAM7-TUR) lineage

Evolution and success of the multi-drug resistant M. tuberculosis SIT41 (LAM7-TUR) lineage

The proposed project “Evolution and success of the multidrug-resistant Mycobacterium tuberculosis SIT41 (LAM7-TUR) lineage” was carried out at the Infection Genetics Emerging Pathogen Evolution Team (IGEPE) under the supervision of Prof. Christophe Sola. Mycobacterium tuberculosis (MTB) is the cause of tuberculosis (TB) in humans. Multidrug resistant tuberculosis (MDR TB) is a major concern for control TB programs. Identification of the MTB lineage is of importance to tuberculosis control as it has shown that strain type may play a role in disease outcome, variation in vaccine efficacy and emergence of drug resistance. MTB strains of Beijing and Latin-American-Mediterranean (LAM) lineages were associated with hyper-transmissibility and drug resistance. In 2013 the European Center for Diseases Prevention and Control (ECDC) effectively lunched molecular surveillance of MDR TB at EU level. Within this EU project the typing of M. tuberculosis strains in Bulgaria confirmed strong association between MDR and SIT41 (TUR) [SIT – Spoligo International Type] MTB lineage. The MDR TB cases with SIT41 strain genotype in Bulgaria increased from 40% to 60% in the period 2007-2013, while the drug sensitive genotype represented only 2%. Statistically 97% of the TB patients infected with drug sensitive SIT41 MTB strain develop MDR tuberculosis. SIT41 is marker genotype for MDR TB. Moreover the project promoted the research career restart of the Fellow by obtaining during the course of the action a Doctor of Sciences degree. The genotyping results were reported and extensively exploited by the Bulgarian TB program and the ECDC for epidemiological surveillance reports and the ECDC database of MDR-TB genotypes. Fifteen publications and congress reports were produced during the course of the Action. The poster presented at the annual congress of the European Society of Mycobacteriology (ESM) was awarded with third price for best congress poster. The conclusions of the project are: - The endemic SIT41 MDR genotype, spreading in Bulgaria, was not found in other countries, suggesting local evolution. - The main characteristic of the Bulgarian SIT41 strains is the 11 VNTR copy number of QUB-26(4052) marker. - Contact tracing analysis could not explain how patients living at a distance of >350 km have identical MIRU-VNTR and cgMLST profiles. - Applying on-going WGS analysis we hope to date the start of this ongoing MDR endemy, to identify true transmissions across the country. The clonal expansion of SIT41 among the MDR-TB patients in Bulgaria remains to be further analyzed. The Host laboratory offered outstanding quality, innovative research opportunities and work in a world-wide laboratory network of excellence (Brazil, South Africa, the Netherlands, Kazakhstan and others).

Data: CORDIS, © European Union