Data integration to close the gap on Prediction of MTB Drug Resistance Mutations

Project Details


Improved diagnosis and treatment are designated priorities of the World Health Organization and
the Centers for Disease Control to address the antimicrobial resistance challenge. These measures
rely on an improved understanding of the mechanisms of resistance acquisition in bacteria.
Especially for new anti-tuberculosis drugs, known genetic mutations poorly predict phenotypic
resistance testing, yet real-time resistance testing is essentially impossible in the endemic areas
most affected. In M. tuberculosis, drug resistance (DR) is caused by protein modifying mutations in
drug targets or in pro-drug to drug converting enzymes. However, the possibility that gene
regulation plays an important role in antimicrobial resistance has yet to be systematically studied.
While most mutations have no impact on drug susceptibility, distinguishing those mutated genes
that drive DR in a patient is essential to assign an effective treatment regimen, typically involving 5
or more drugs for 9+ months. Knowledge of genes and pathways on which DR mutations operate
can also resolve the discordance between genotypic and phenotypic drug susceptibility testing and
promises to finally replace the slow, more expensive and biohazardous assay susceptibility testing.
Effective start/end date20/10/2020/10/21


  • DIVERSE KLANTEN: €24,485.00