RNA biomarkers discovery for ultra-fast drug synergy and susceptibility testing in the mycobacterium avium complex.

Pulmonary infections caused by the Mycobacterium avium–intracellulare complex (MAC) are slow and progressive, and increasingly prevalent in developed countries. They can be cured, but their treatment consists of a 12 months multidrug regimen. A key issue standing in the way of designing more effective treatment regimens is the lack of a diagnostic tool for drug susceptibility testing (DST) in MAC. Current methods are slow (3-5 weeks), poorly reproducible and their results are difficult to interpret by clinicians. In this project, we will design a novel DST for MAC infections. It is based on the idea that a susceptible bug will feel stress under attack of an antibiotic, and a resistant one will not. The test is based on multiplex measurements of relative quantities of antibiotic-specific RNA biomarkers after short exposure to the drug. This test is unlike any test on the market. The project start fundamental, with transcriptional analyses of MAC cells under antibiotic stress. We will identify drug-specific sets of stress genes, and convert these into a Luminex-based format for multiplex quantification. The test parameters will be optimized using contemporary clinical strains, in collaboration with the National Reference Centre for Mycobacteria. Finally, we will apply our platform to identify synergetic interaction between novel and old compounds to derive optimal drug combinations with the strongest possible effect on clinical MAC strains.

Keywords:TRANSCRIPTOMICS, PULMONARY MEDICINE

Disciplines:Infectious diseases, Microbial diagnostics

Project type:Collaboration project