Population genomics of Mycobacterium tuberculosis in HIV-infected and HIV-negative patients: the nationwide molecular-epidemiological tuberculosis study (SHCS no. 740)

In recent years, there have been major advances in molecular epidemiology. It is likely that whole genome sequencing will become the new standard genotyping method in the near future because of the higher discriminatory power and the decreasing cost of DNA sequencing. Here, we propose to analyse the M. tuberculosis whole genome sequences from a well-described nationwide molecular-epidemiological study in Switzerland 2000-2008.

In this study, we will generate full genome sequences of all the M. tuberculosis isolates. Sequencing data will be analysed using phylogenomic and population genomic techniques. We have previously performed a nationwide study on the molecular and clinical epidemiology of TB in Switzerland. Briefly, we analyzed 520 TB cases diagnosed between 2000 and 2008. We determined drug resistance by semiquantitative drug susceptibility testing of first-line drugs and by drug resistance genotypes, and recent transmission by spoligotyping and 24-loci MIRU-VNTR. In addition, we collected socio-demographic, clinical and laboratory data. This study will define for the first time the genetic population structure in a well-characterized M. tuberculosis nation-wide strain collection from HIV-infected and HIV-negative TB patients. Importantly, the present study will provide the basis for further molecular-epidemiological studies using whole genome sequences in the context of HIV in Switzerland and sub-Saharan Africa.