Mycobacterium abscessus is a particularly dangerous pathogen for people with cystic fibrosis (CF), and there are currently no effective drugs available to treat it. For this reason, there is an urgent need to identify new drugs to target this bacterium.
Thanks to previous projects (FFC#19/2018, FFC#14/2020 and FFC#18/2021), the research group has identified a new bactericidal compound called VOMG, which blocks the cell division of the bacterium and for which two patents have already been filed. 

In this new project, researchers investigated the mechanism of action of VOMG to validate its activity on the FtsZ enzyme, which is involved in cell division: VOMG is actually capable of inhibiting FtsZ in vitro. The compound is also active against M. abscessus and other pathogens, such as Mycobacterium avium, Mycobacterium tuberculosis, Acinetobacter baumannii, Staphylococcus aureus and Escherichia coli.

They then evaluated the activity of the main antibiotics used against M. abscessus in the model using an in vitro assay called Granuloma-like structure, in which they reproduced the structure formed by immune cells characteristic of M. abscessus infections. Experiments conducted on the granuloma showed that two antibiotics, clarithromycin and bedaquiline, are the most active against M. abscessus.

VOMG was then tested in combination with the antibiotic amikacin: VOMG is not active within granuloma cells but, in combination with amikacin, it enhances its activity by reducing bacterial growth. 

Finally, an animal model infected with the bacterium was used to evaluate the activity of VOMG in vivo: the VOMG-amikacin combination proved to be effective in vivo as well.

In the continuation of this project (FFC#11/2025), both the transport to the lung and the intracellular activity of VOMG will be improved by encapsulating it in “shuttle” particles called liposomes.
This line of research paves the way for the development of a new treatment for M. abscessus infections, particularly for people with cystic fibrosis. 

Publications

• The novel drug candidate VOMG kills Mycobacterium abscessus and other pathogens by inhibiting cell division.
  International Journal of Antimicrobial Agents, 2024

Patents

• Pyridine-2-thiol 1-oxide derivatives and their use for treatment of mammalian infections caused by Mycobacterium or fungi. WO 2024/083764 A1; Entry into the EU and US national phases after PCT
• A pharmaceutical combination for the treatment of lung infections in subjects with cystic fibrosis. IT National patent; PCT extension filed: PCT/EP2025/059935