Mycobacterium abscessus (Mab) is a bacterium resistant to many antibiotics; it is often involved in chronic lung infections of people with cystic fibrosis (CF), and is one of the causes of mortality in this disease. The complex therapeutic management of Mab infections necessitates the development of new strategies.
Furthermore, macrophages, cells of the immune system that are responsible for eliminating bacteria, have been shown to be defective in CF.

The researchers propose to find a new combined therapeutic formulation that restores the immune response of the CF person infected with the bacterium and eliminates Mab by antibiotics.

Liposomes (small vesicles that can be administered aerosolically) containing bioactive lipids, which can increase immune function against lung infections due to multi-resistant bacteria, have been developed previously. In this study, liposomes composed of phosphatidylserine and/or phosphatidyl inositol 5-phosphate (ABL/PS or ABL/PI5P) were used.

In this project, macrophages, derived from healthy donors or people with CF treated or not with Kaftrium, were infected with two variants of Mab (called ATCC19977 and CP285). The cells were then treated in vitro with liposomes in combination or not with Kaftrio or the antibiotic amikacin (AMK).
The effects of the individual stimuli or their combinations were assessed by quantifying the replication of Mab within cells, the maturation of phagolysosomes (vesicles that encapsulate and eliminate the bacterium) and the development of inflammation. 
The combined ABL/PS-AMK treatment was evaluated in vivo in terms of mycobacterial elimination and recruitment of macrophages, one of the steps in the inflammation process. 

The researchers observed that ABL/PI5P and ABL/PS liposomes induced a decrease in Mab viability in macrophages from both Kaftrio-treated and untreated CF patients, without interfering with the drug’s effect in vitro. The combination of liposomes with AMK proved effective both in vivo and in vitro in controlling infection.
The results show that treatment with ABL/PI5P and ABL/PS liposomes, in combination with antibiotics, may represent a valid alternative therapeutic strategy for the control of Mab infection, both in persons with CF who receive Kaftrio treatment but, above all, in all persons with CF who cannot benefit from such drug treatment.

Given the advanced development of the liposomes used, whose efficacy has been validated both in vitro and in vivo, future prospects include the initiation of more in-depth preclinical studies to collect safety data on ABL/PS and ABL/PI5P liposomes in anticipation of phase I clinical trials.