Inhibitors of Ca2+ and K+ transport enhance intracellular killing of M. tuberculosis by non-killing macrophages.
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.
Martins
Marta
M
Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, 1349-008 Lisboa, Portugal.
Viveiros
Miguel
M
Amaral
Leonard
L
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
D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D010042:Ouabain; D012110:Reserpine; D014700:Verapamil; D013881:Thioridazine