"-" - The role of region-specific SNPs in virulence genes in Mycobacterium tuberculosis drug resistance

07 August 2017

Project coordinator:

Valery N. Danilenko

Vavilov Institute of General Genetics, RAS


Project partners:

Lingyun Shao

Department of Infectious Diseases, Huashan Hospital, affiliated to Fudan University


Martie van der Walt

TB Platform unit, South African Medical Research Council

South Africa

Funding agencies:

MON (Russia), NSFC (China), NRF (South Africa)


Tuberculosis (TB), the infectious disease caused by the bacillus Mycobacterium tuberculosis (MTB), remains a significant global public health threat. As of 2015, TB is now the worldwide leading cause of death from an infectious disease. Approximately one third of the world’s population (1.8 billion people) is infected with MTB.

The use of antibiotics as well as the modulation of the immune status of the human population due to the spread of various chronic diseases including but not limited to HIV in the latest century lead to significant structural changes within MTB resulting in the emergence of new lineages characterized by enhanced drug resistance and virulence. Infection by MTB strains with multidrug (MDR) and extensive drug resistance (XDR) is associated with bad treatment outcome. In January 2013, the Ministers of Health of BRICS countries issued a joint Communique in Delhi in which they recognized the high burden of MDR-TB in their countries (>60% of the global burden). In the last decade the selection of new Mycobacterium tuberculosis sublineages is driven by a number of factors, among which the use of antibiotics and the adaptation of MTB to various immune statuses are the main ones.

This multifactorial evolution of MTB lead to a spread of “successful” clones in different geographic locations, such as the Beijing B0/W-148 in Russia, Beijing modern in China and F15/LAM4/KZN in South Africa.

Our preliminary research shows the emergence of new sublineages within the Beijing B0/W-148 and Beijing modern lineages (Beijing B0/N-90 and Beijing modern-4, respectively), which are associated with drug-resistant phenotypes and harbor a number of specific mutations in virulence-associated genes. Enhanced virulence may be linked to drug resistance. One of the main examples of genes involved in both aspects is WhiB7, which controls the expression of a regulon containing genes responsible as for intrinsic drug resistance, as well as for virulence. Other examples may include  ecc5 type VII excretion system and toxin-antitoxin sytems.

Our project aims to identify SNPs in virulence-associated genes, associated with drug-resistant phenotype of M. tuberculosis belonging to geographical-specific lineages that emerged in the era of antibiotics.

Each partner will analyze SNPs in virulence genes among the successful MTB lineages specific to their country, which will allow to identify new mechanisms of drug resistance driven by virulence genes and to develop new diagnostic tools to detect such strains, which emerged in the era of antibiotics and are well adapted to hosts in specific geographic regions, thus being epidemiologically dangerous.

One of the main advantages of this international collaboration is that all the partners are members of the TBResist consortium, and will have access to the consortium’s database of more than 800 sequenced and well-characterized MTB genomes, and will allow filling up the database with newly sequenced within this project MTB genomes.