Chloroquine and the fungal phagosome.
The antimalarial drug chloroquine accumulates inside the macrophage phagolysosome by ion trapping where it exerts potent antifungal activity against Histoplasma capsulatum and Cryptococcus neoformans by distinct mechanisms. Chloroquine inhibits growth of H. capsulatum by pH-dependent iron deprivation, whereas it is directly toxic to C. neoformans. Clearly, clinical studies are required to document the potential therapeutic efficacy of chloroquine or related congeners as adjuvant therapy in fungal disease. Moreover, the diversity of pathogenic microorganisms inhibited and/or killed by chloroquine makes this drug an attractive candidate for prophylactic therapy.
Weber
S M
SM
Evans Memorial Department of Clinical Research, Boston University School of Medicine, Massachusetts 02118, USA.
Levitz
S M
SM
Harrison
T S
TS
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D003453:Cryptococcosis / Q000188:drug therapy / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects*; D006658:Histoplasma / Q000187:drug effects*; D006660:Histoplasmosis / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism; D051379:Mice; D010588:Phagosomes / Q000187:drug effects* / Q000382:microbiology
D000935:Antifungal Agents; D002738:Chloroquine; D007501:Iron