INhibiting Siderophore Production In REsistant Non Tuberculous Mycobacteria – an innovative strategy for the treatment of lung infections: Nontuberculous mycobacteria in cystic fibrosis (CF): scouting molecules against M. abscessus iron acquisition pathways

The resistance of the most relevant nontuberculous mycobacterium, M. abscessus, against conventional therapies is globally rising, especially among cystic fibrosis patients. Iron is critical for pathogen growth and virulence and thus the biosynthesis of iron chelators is a innovative target to select inhibitors with bacteriostatic activity. In this context, we plan to identify novel compounds targeting an enzyme of the mycobactin biosynthetic process, the salicylate synthase, by structure-based drug design.

CNR will perform homology modelling and virtual screening using three different libraries of compounds and biophysical studies and binding screening on M. abscessus salicylate synthase, using the compound libraries synthesized by the partners toquantitatively characterize both kinetics and affinity. CNR will also obtain structural data by crystallographic studies on the apo enzyme and its complexes with the selected leads or by automated docking simulations