The Acidocalcisome as a Target for Chemotherapeutic Agents in Protozoan Parasites

Acidocalcisomes are acidic organelles rich in calcium and phosphorus that have been conserved from bacteria to man. In parasitic protozoa acidocalcisomes possess enzymes that are absent or different from their mammalian counterparts and could be potential targets for chemotherapy, such as the vacuolar proton translocating pyrophosphatase, and the soluble inorganic pyrophosphatase, both of which are inhibited by pyrophosphate analogs (bisphosphonates). In addition, a number of drugs, including bisphosphonates, and diamidines appear to accumulate in these organelles and/or induce an increase in their numbers. The mechanism of action of bisphosphonates, however, is by inhibition of the isoprenoid pathway and more specifically the prenyl diphosphate synthases.