Unit | Tuberculosis Research

TB Research in the BSL3-Laboratory at Swiss TPH
The TB research unit follows a systems approach

Our Research Focus

The Tuberculosis Research Unit focuses on the causes and consequences of genetic diversity in the Mycobacterium tuberculosis complex (MTBC), the bacteria that cause tuberculosis (TB). We pursue a systems epidemiology approach, in which we combine various disciplines to study the global diversity of the MTBC, the evolutionary forces that drive this diversity, as well as the phenotypic consequences of this diversity for the biology and the epidemiology of TB. 

Our research comprises three complementary arms:

  • The global population structure of the MTBC
  • Evolution and ecology of drug-resistant MTBC
  • Genomic epidemiology of TB

 

Partnerships

An important part of this work relies on our long-term partnerships with collaborators in TB-endemic countries. These include the Ifakara Health Institute in Tanzania, the Noguchi Memorial Institute for Medical Research in Ghana, and the National Centre for Tuberculosis and Lung Disease in Georgia.

Sébastien Gagneux

Sébastien Gagneux, Associate Professor, PhD

The Global Population Structure of the MTBC

The human-adapted MTBC comprises seven phylogenetic lineages that are associated with different regions of the world. We use comparative whole genome sequencing to study the differences between these lineages and the evolutionary forces shaping this diversity. We combine various –omics technologies with functional assays and epidemiological data to investigate the phenotypic consequences of this diversity.

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The Ecology and Evolution of Drug-resistant MTBC

Drug resistance poses a growing threat to global health. When drug-resistant bacteria first emerge, they are often less transmissible than susceptible strains – this is because drug resistance in bacteria is often associated with a reduction in Darwinian fitness. However, evolution is a continuous process, and drug-resistant bacteria readily adapt and regain the ability to transmit. This process is mediated by compensatory mutations. 

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Genomic epidemiology of TB

Recent advances in whole-genome sequencing have revolutionized molecular epidemiological investigation of TB. We use such genomic epidemiological approaches to study the transmission dynamics of TB in Switzerland and in TB-endemic countries. We also explore the micro-evolution of MTBC in individual patients during treatment. 

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Stucki D et al. Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages. Nat Genet. 2016;48(12):1535-1543. DOI: 10.1038/ng.3704

Petrone L et al. Blood and urine inducible protein 10 as potential markers of disease activity. Int J Tuberc Lung Dis. 2016;20(11):1554-1561. DOI: 10.5588/ijtld.16.0342

Dominguez J et al. Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET/RESIST-TB consensus statement. Int J Tuberc Lung Dis. 2016;20(1):24-42. DOI: 10.5588/ijtld.15.0221

Andre E et al. Consensus numbering system for the rifampicin resistance-associated rpoB gene mutations in pathogenic mycobacteria. Clin Microbiol Infect. 2016(In press). DOI: 10.1016/j.cmi.2016.09.006

Otchere I.D et al. Detection and characterization of drug-resistant conferring genes in Mycobacterium tuberculosis complex strains: a prospective study in two distant regions of Ghana. Tuberculosis (Edinb). 2016;99:147-154. DOI: 10.1016/j.tube.2016.05.014