Researchers set up different in vitro infections with MA reference strain (ATCC 19977) on human pro-monocytic THP-1 leukemia cell line (dTHP-1) to investigate the effect of ABLs on phagocytic mechanism. They validated the effect of different ABLs (ABL/PA, ABL/PI3P, ABL/PI5P, ABL/AA, ABL/LBPA, and ABL/S1P) in vitro with dTHP-1 cells and in C57Bl/6 mice chronically infected with MA. In vitro results showed that ABL/PA, ABL/PI3P, and ABL/PI5P were the most more effective to increase the phagocytic and the intracellular microbicidal activity of human dTHP1 infected with MA. In C57Bl/6 mice chronically infected with MA the treatment with the best 3 ABLs selected in in vitro experiments showed to statistically reduce both lungs bacterial burden and inflammatory response. In this way, researchers conclude that ABLs could represent a novel immunotherapeutic strategy to treat pulmonary infection by drug-resistant MA in CF patients.
In the next project, FFC#17/2019 researchers will evaluate the synergistic effect of ABLs with different antibiotics (amikacin, clarithromycin, and cefoxitin) commonly used in the treatment of MA infection, in vitro and in vivo experiments. The perspective is to identify a combined treatment that may enhance the host innate antibacterial response against MA infection and to increase the killing capacity of macrophages with CF mutations.