phosphatidylinositol-5-phosphate and Cystic-Fibrosis
phosphatidylinositol-5-phosphate has been researched along with Cystic-Fibrosis* in 1 studies
Other Studies
1 other study(ies) available for phosphatidylinositol-5-phosphate and Cystic-Fibrosis
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Combined Host- and Pathogen-Directed Therapy for the Control of Mycobacterium abscessus Infection.
Mycobacterium abscessus is the etiological agent of severe pulmonary infections in vulnerable patients, such as those with cystic fibrosis (CF), where it represents a relevant cause of morbidity and mortality. Treatment of pulmonary infections caused by M. abscessus remains extremely difficult, as this species is resistant to most classes of antibiotics, including macrolides, aminoglycosides, rifamycins, tetracyclines, and β-lactams. Here, we show that apoptotic body like liposomes loaded with phosphatidylinositol 5-phosphate (ABL/PI5P) enhance the antimycobacterial response, both in macrophages from healthy donors exposed to pharmacological inhibition of cystic fibrosis transmembrane conductance regulator (CFTR) and in macrophages from CF patients, by enhancing phagosome acidification and reactive oxygen species (ROS) production. The treatment with liposomes of wild-type as well as CF mice, intratracheally infected with M. abscessus, resulted in about a 2-log reduction of pulmonary mycobacterial burden and a significant reduction of macrophages and neutrophils in bronchoalveolar lavage fluid (BALF). Finally, the combination treatment with ABL/PI5P and amikacin, to specifically target intracellular and extracellular bacilli, resulted in a further significant reduction of both pulmonary mycobacterial burden and inflammatory response in comparison with the single treatments. These results offer the conceptual basis for a novel therapeutic regimen based on antibiotic and bioactive liposomes, used as a combined host- and pathogen-directed therapeutic strategy, aimed at the control of M. abscessus infection, and of related immunopathogenic responses, for which therapeutic options are still limited. Topics: Amikacin; Animals; Anti-Bacterial Agents; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Female; Humans; Liposomes; Macrophages; Male; Mice; Mice, Inbred C57BL; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Phagosomes; Phosphatidylinositol Phosphates; Reactive Oxygen Species | 2022 |