Chemical Genomics of Intracellular Mycobacteria (CGIM)

The team projects focus on Tuberculosis (TB). TB is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that results in millions of deaths annually worldwide and an increased incidence of reported drug-resistant cases. New drugs as well as novel drug targets are urgently needed. In order to realize radical advances in TB drug discovery, a better understanding of Mtb persistence and latency are necessary. In particular, this requires detailed elucidation of the mechanisms by which host cells control intracellular replication upon infection by pathogenic mycobacteria.

The team’s overall objective is to better understand TB pathogenesis to develop powerful strategies with enhanced efficacy, which allow the host to minimize or eradicate colonization by Mtb. The comprehensive picture of the molecular interactions between Mtb effectors and host cell proteins is necessary to generate the molecular tools for the development of antivirulence compounds that affect specific host pathways.

Main objectives

Mechanisms of Mycobacteria-Host Interactions

  • Bacterial virulence factors

ESX-1 secretion system/quantification of ESX-1 protein complex within phagocytes.

LppM secreted protein/macrophages/control of acidification and cytokine secretion/TLR2 dependent.

  • Cellular pathways

M. tuberculosis/lung epithelial cells/uptake/ rearrangements of the actin cytoskeleton /ArfGAP1.

M.. tuberculosis/macrophages/control of acidification/Tirap/CISH/TLR2.

M. tuberculosis/macrophages/metabolic reprogramming/IRG1/itaconate.

Therapeutic Innovation for Tuberculosis (TB) Drug Discovery

  • Novel active compounds from private companies, European PME,  international and national collaborations.
  • Novel delivery means of combination . Use of nanoparticles for small molecules encapsulation and pulmonary delivery.
  • New in vitro respiratory model microfluidic Lung-on-a-Chip device reconstituting the alveolar-capillary tissue interface.
  • Anti-microbial Peptides putative antitubercular agents from deep sea animals–Pompeii worm.

M. ulceransANALGESIA

Cellular pathways, M. ulcerans/neurons/analgesia/AT2R-Traak