Phosphatidylinositol 5-phosphate-loaded-apoptotic body-like liposomes for Mycobacterium abscessus infections management in people with cystic fibrosis

Mycobacterium abscessus (Mab) is an opportunistic nontuberculous mycobacterium, intrinsically resistant to a wide range of antibiotics, responsible of difficult-to-treat pulmonary infections in vulnerable patients, like those with Cystic Fibrosis (CF). Impaired macrophage function in people with CF (pwCF) plays a pivotal role in defective bacterial killing. Despite cystic fibrosis conductance regulator (CFTR) modulators like Kaftrio (ETI) are being widely used to improve pwCF quality of life and clinical outcome, there still is a proportion of pwCF whose CFTR mutations are incompatible for such pharmacological treatment. In this study, we have investigated a potential therapeutic strategy for managing chronic Mab infections, particularly in pwCF who are ineligible for standard ETI treatments. Results show that both liposome ABL/PI5P and ETI in vitro treatments reduce Mab intracellular viability in macrophages from pwCF undergoing or not ETI regimen. Notably, no synergistic, additive or interference effect were shown when the treatments were combined. Furthermore, the in vitro stimulation with ABL/PI5P of in vitro Mabinfected macrophages from pwCF who did not receive ETI lead to a significant reduction in intracellular mycobacterial viability and the combination of liposomes with amikacin resulted in a further significant reduction compared to single treatments. These findings suggest that ABL/ PI5P liposomes, in combination with antibiotics, may represent a valuable therapeutic treatment which can be developed for the control of Mab infections in both patients receiving standard ETI therapy and, most importantly, in pwCF who cannot benefit from such pharmacological treatment.