Microbial Enzymology and Drug Targets Laboratory

Enzimologia microbica e bersagli farmacologici

Referent: Prof. Laurent Chiarelli

Co-workers: Giovanni Stelitano

 

The spread of antimicrobial resistance (AMR) is recognized as a major threat to global health and to healthcare systems, being the cause for almost 700,000 deaths annually. For these reasons there is an urgent need of developing new drugs with novel mechanism of action. In our laboratory we are investigating and characterizing bacterial enzymes as target of compounds for the development of novel inhibitors, as well as enzymes involved in drug resistance mechanisms. The work is particularly focused on Mycobacteria, such as M. tuberculosis the etiological agent of tuberculosis, and on M. abscessus a pathogen causing opportunistic infections patients with lung diseases, such as cystic fibrosis. Currently, we are studying different enzymes , that are essential for the mycobacterial growth, for the development of novel antimycobacterial agents. Among them, the DprE1-DprE2 complex, involved in cell wall synthesis, and the protein FtsZ involved in cell division. Moreover, a strategy to overcome the insurgence of resistance could be the antivirulence therapy, namely the use of compounds targeting pathways required for pathogenesis, but not essential for microbial growth. This approach does not aim to kill the pathogens but rather to prevent an attack on the host, thus potential drugs would not exert a selective pressure, reducing resistance phenomena. In this context, we are investigating to develop inhibitors of two enzymes that represent interesting virulence factors: the phosphatase PtpB, and the salycilate synthase.

Main collaborations:

  • Villa S and Meneghetti M (Department of Pharmaceutical Sciences, University of Milan),
  • Makarov V (Bakh Institute of Biochemistry, Russian Academy of Science, Moscow, Russia),
  • Qiao C (College of Pharmaceutical Sciences, Soochow University, China),
  • Mikusova K (Comenius University in Bratislava, Department of Biochemistry, Bratislava, Slovacchia),
  • Bellinzoni M (Institut Pasteur Paris, France).