An international tuberculosis consortium—including the Research Center Borstel—has succeeded in developing a standardised and internationally recognised method that is able to better predict in tuberculosis bacteria resistance in future. Their findings were published in the European Respiratory Journal.
Tuberculosis (TB) is one of the most dangerous infectious diseases worldwide: in 2016 alone, 10.4 million contracted TB and 1.7 million died of the consequences of infection. A quarter of these cases of death were due to resistant TB strains, the so-called Mycobacterium tuberculosis complex (MTBC). The spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains poses a major global challenge. This is because effective treatment of MDR/XDR-TB patients is very difficult owing to limited availability of comprehensive diagnostic methods, amongst other things.
The current study uses a standardised approach to interpret changes in the genome (mutations) of clinical MTBC strains that are associated with multidrug-resistance. Based on a systematic and extensive analysis of over 1.600 data sets, the 30 participating research establishments in the consortium established an initial list of validated multidrug-resistance associated mutations found in strains of the Mycobacterium tuberculosis complex. The most important mutations that permit predictions of resistance to first and second line tuberculosis drugs were determined.
The study findings support employing molecular biological methods for resistance testing, as is currently the developing trend. Genome sequencing of clinical MTBC strains is increasingly being employed for comprehensive predictions of resistance and individualised therapy of MDR/XDR-TB patients.
“The availability of a curated and validated database for interpreting resistance associated mutations constitutes an essential prerequisite for using genome sequencing as a diagnostic method. It makes targeted and individualised treatment of MDR/XDR-TB patients possible in the first place,” explains Stefan Niemann, Head of the ‘Molecular and Experimental Mycobiology’ research group at the Research Center Borstel and Coordinator of the research field “Tuberculosis” at the German Center for Infection Research (DZIF).
The validation system for resistance-associated mutations developed in this study enables significantly improved clinical interpretations of genetic changes in MTBC strain genomes. This is a major advancement in individualised TB treatment. For this reason, the new approach has been integrated into the “Relational Sequencing for TB (ReSeqTB) platform (platform.reseqtb.org)”, a global, WHO funded database.