Whole genome sequencing for M/XDR tuberculosis surveillance and for resistance testing.
Walker T., Merker M., Kohl T., Crook DW., Niemann S., Borstel FZ., Peto P.
Whole genome sequencing (WGS) can help relate Mycobacterium tuberculosis genomes to one another to assess genetic relatedness and infer the likelihood of transmission between cases. The same sequence data is now increasingly being used to predict drug resistance and susceptibility as well. Controlling the spread of tuberculosis and providing patients with the correct treatment are central to the World Health Organization's target to 'End TB' by 2035, to which the global prevalence of drug resistant tuberculosis remains one of the main obstacles to success. WGS has so far been applied largely to drug susceptible strains for the purposes of understanding transmission, leaving a number of analytic considerations before transferring what has been learnt from drug susceptible disease to drug resistant tuberculosis. We discuss these potential problems here, alongside some of the challenges to characterising the Mycobacterium tuberculosis 'resistome' - the optimal knowledgebase required for WGS-based assays to successfully direct individualised treatment regimens through the prediction of drug resistance and susceptibility in the future.