Nontuberculous mycobacteria (NTM) are important pathogens, which are responsible for a wide spectrum of clinical manifestations; the NTM species most commonly identified are Mycobacterium avium complex and Mycobacterium abscessus complex (MABSC). The incidence of pulmonary disease caused by MABSC members is dramatically increasing especially among cystic fibrosis patients worldwide, with M. abscessus subsp. abscessus (M. abscessus) becoming the most worrisome. M. abscessus infections are characterized by the formation of granulomas. These are organized structures of macrophages, epithelioid cells and multinucleated giant cells, surrounded by a ring of lymphocytes. Their function is to localize and contain mycobacteria while concentrating the immune response to a limited area. During the life in the granulomas, bacteria are hypothesized to go through a remodeling of their metabolism likely helping them to become more tolerant to different stress, including that due to drugs. M. abscessus treatment is a combinational and highly toxic therapy up to 2 years long. Treatment failure is associated with unfavourable progression and to an accelerated lung function decline. Consequently, new active and less toxic drugs are urgently needed.
Out of more than 700 compounds ad hoc synthetized within previous projects, VOMG was the only hit molecule active against M. abscessus in vitro, M. abscessus biofilm and in vivo with a high bactericidal activity. Project researchers recently discovered that it targets cell division, by inhibiting the FtsZ protein.
VOMG has been patented with the co-ownership of FFC Ricerca thanks to the potential of its activity in vitro, in vivo and against biofilm. The obtained results show that VOMG has features to be a drug candidate against M. abscessus with the potential to be included in regimens to treat M. abscessus lung disease. 

In this project, researchers aim to: 

• study the mechanism of action of VOMG in depth
• evaluate the activity of VOMG alone and in combination with amikacin in M. abscessus infected mice using different methods 
• study the activity of VOMG alone or in combination with amikacin in a granuloma-like structure model induced by M. abscessus infection. Our findings will pave the wave for the development of new potentialtherapeutic and antimicrobial treatments against M. abscessus infections in particular for cystic fibrosis individuals.