Infections caused by Mycobacterium abscessus (Mab) are among the most complex and difficult to eliminate, especially for people with cystic fibrosis, due to Mab’s innate ability to resist many of the drugs used. This reduces the effectiveness of commonly used therapies and makes treatment of the infection long and debilitating.

This project was aimed at finding new approaches to eliminate Mab by promoting the antimicrobial capabilities of the human immune system, particularly macrophages, cells found in the lungs that recognize pathogens and coordinate their elimination.

The researchers infected a cellular model similar to alveolar macrophages with Mab and then treated it with non-toxic concentrations of Panobinostat. Doing this, they tested its effectiveness in re-educating immune cells to contain and eliminate Mab infection.
High-resolution microscopy was used to observe physical changes within individual cells. In addition, active and inactive proteins and genes were analyzed to understand how they react when there is an infection.
The analyses carried out made it possible to define how Panobinostat re-educated the immune cells and to verify whether any toxic effects arose. 

Finally, the effectiveness of the treatment in reducing the infection rate was evaluated.
It was observed that in infected macrophages, Panobinostat reduces the accumulation of lipids, macromolecules essential for the intracellular growth of the bacterium: this reduced intracellular accumulation reduces the replicative capacity of Mab and therefore the continuation and spread of the infection.

The next step will be to validate the effectiveness of Panobinostat in an animal model to confirm that this antimicrobial effect is also achieved in a complex organism.
The ultimate goal is to develop an innovative therapy that exploits the innate ability of macrophages to defend the body against infection.

Publications

• Epigenetic Modulation by Panobinostat Primes Immune Readiness in Alveolar Macrophages.
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