| Autor: |
I-Fang, Tsai, Chiu-Ping, Kuo, Andrew B, Lin, Ming-Nan, Chien, Hsin-Tsung, Ho, Tsai-Yin, Wei, Chien-Liang, Wu, Yen-Ta, Lu |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Respirology (Carlton, Vic.). 22(3) |
| ISSN: |
1440-1843 |
| Popis: |
Tuberculosis (TB) risk might be increased in patients with diabetes by factors other than hyperglycaemia, such as dyslipidaemia. Host lipids are essential energy sources used by mycobacteria to persist in a latent TB state. A potential therapy targeting cholesterol catabolism of mycobacteria has been proposed, but the potential of cholesterol-lowering drugs as anti-TB therapy is unclear. The purpose of this study was to determine the effects of ezetimibe, a 2-azetidinone cholesterol absorption inhibitor, on intracellular mycobacteria survival and dormancy.Intracellular mycobacteria survival was determined by measurements of ATP activity and colony-formation units (CFUs). Gene expression profiles of hypoxia-induced dormant Mycobacterium tuberculosis (Mtb) were analysed by real-time PCR. Flow cytometry and microscopy analysis were used to measure the lipid loads of human macrophages with or without ezetimibe treatment. QuantiFERON-TB Gold In-Tube (QFT-G-IT) assays were performed to diagnose latent TB infection. The levels of intracellular cholesterol/ triglyceride were measured by an enzymatic fluorometric method.Ezetimibe was capable of effectively lowering intracellular growth of Mtb and hypoxia-induced dormant Mtb. There was a significant decrease in Mtb growth in leucocytes from ezetimibe-treated patients with diabetes in terms of ATP levels of intracellular mycobacteria and CFU formation. Also, patients receiving ezetimibe therapy had a lower prevalence of latent TB and had lower intracellular lipid contents.Ezetimibe, which is a currently marketed drug, could hold promise as an adjunctive, host-directed therapy for TB. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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