title: Potential effect of ezetimibe against Mycobacterium tuberculosis infection in type II diabetes.
abstract: 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.
authors.affiliation: Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: I-Fang
authors.initials: IF
authors.lastname: Tsai
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chiu-Ping
authors.initials: CP
authors.lastname: Kuo
authors.affiliation: Biology Department, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lin
authors.affiliation: Department of Endocrinology and Metabolism, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Ming-Nan
authors.initials: MN
authors.lastname: Chien
authors.affiliation: Department of Laboratory Medicine, MacKay Memorial Hospital, Taipei, Taiwan.|Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.
authors.forename: Hsin-Tsung
authors.initials: HT
authors.lastname: Ho
authors.affiliation: Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Tsai-Yin
authors.initials: TY
authors.lastname: Wei
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.|MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.
authors.forename: Chien-Liang
authors.initials: CL
authors.lastname: Wu
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.|Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.
authors.forename: Yen-Ta
authors.initials: YT
authors.lastname: Lu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D015169:Colony Count, Microbial; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D000069438:Ezetimibe / Q000627:therapeutic use*; D006801:Humans; D055985:Latent Tuberculosis / Q000517:prevention & control; D007962:Leukocytes / Q000382:microbiology; D050356:Lipid Metabolism / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D059467:Transcriptome; D014280:Triglycerides / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy*
chemical_list: D000924:Anticholesteremic Agents; D014280:Triglycerides; D000255:Adenosine Triphosphate; D002784:Cholesterol; D000069438:Ezetimibe
keywords: cholesterol; diabetes mellitus; foam cells; host-pathogen interactions; latent tuberculosis