Journal Article

Conditional Lethality of the Diprotic Weak Bases Chloroquine and Quinacrine against <i>Cryptococcus neoformans</i>

Thomas S. Harrison, George E. Griffin and Stuart M. Levitz

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 182, issue 1, pages 283-289
Published in print July 2000 | ISSN: 0022-1899
Published online July 2000 | e-ISSN: 1537-6613 | DOI: https://dx.doi.org/10.1086/315649
Conditional Lethality of the Diprotic Weak Bases Chloroquine and Quinacrine against Cryptococcus neoformans

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Chloroquine at 10 μM enhances the activity of macrophages against Cryptococcus neoformans but does not directly inhibit cryptococcal growth. The antifungal activity of higher chloroquine concentrations likely to be found within the acidic cryptococcal phagosome was tested. Concentrations of ⩽30 μM inhibited cryptococcal growth, and there was fungal killing at concentrations of ⩽100 μM. Activity was dependent on physiologic temperature and pH. Quinacrine was 50-fold more active than chloroquine, and concentrations as low as 100 nM enhanced macrophage anticryptococcal activity. Quinacrine was concentrated within a vacuolar system within the fungal cell and highly concentrated within intracellular C. neoformans. Ammonium chloride and bafilomycin A both inhibited cryptococcal growth, suggesting that the activity of chloroquine and quinacrine may in part be due to disruption of pH-dependent processes. These findings add to the known spectrum of activity of chloroquine and quinacrine. These, and related compounds, may have utility for the treatment of cryptococcosis.

Journal Article.  4922 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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