title: Inhibitors of Ca2+ and K+ transport enhance intracellular killing of M. tuberculosis by non-killing macrophages.
abstract: BACKGROUND
  Human monocyte-derived macrophages that have little killing activity of their own kill intracellular Staphylococcus aureus when cultured in the presence of inhibitors of calcium and potassium efflux pumps. The aim of this study was to evaluate the effect of inhibitors such as ouabain, reserpine and verapamil in the killing activity of macrophages infected with Mycobacterium tuberculosis.
  
  
  METHODS
  Macrophages obtained from peripheral blood were infected with M. tuberculosis ATCC27294 H37Rv and treated with reserpine, ouabain and verapamil.
  
  
  RESULTS
  After three days post-infection, macrophages treated with the inhibitors demonstrated an enhancement of the killing activity destroying the internalized bacteria.
  
  
  CONCLUSIONS
  Whereas drugs that target the bacterium are predicted to lose effectiveness due to mutation of the bacterial target, drugs that enhance killing by macrophages that normally do not kill mycobacteria may yield a more effective form of infections therapy caused by multidrug resistant M. tuberculosis.
authors.affiliation: Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, 1349-008 Lisboa, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Martins
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
mesh_terms: D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology; D050296:Microbial Viability / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D013881:Thioridazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D010042:Ouabain; D012110:Reserpine; D014700:Verapamil; D013881:Thioridazine