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- W2012196995 abstract "Recalcitrant microbial infections demand new therapeutic options. Here we present an approach that exploits two prongs of the host immune cell antimicrobial response: the oxidative burst and the compartmentalization of copper (Cu) within phagolysosomes. The prochelator QBP is a nontoxic protected form of 8-hydroxyquinoline (8HQ) in which a pinanediol boronic ester blocks metal ion coordination by 8HQ. QBP is deprotected via reactive oxygen species produced by activated macrophages, creating 8HQ and eliciting Cu-dependent killing of the fungal pathogen Cryptococcus neoformans in vitro and in mouse pulmonary infection. 8HQ ionophoric activity increases intracellular Cu, overwhelming the Cu-resistance mechanisms of C. neoformans to elicit fungal killing. The Cu-dependent antimicrobial activity of 8HQ against a spectrum of microbial pathogens suggests that this strategy may have broad utility. The conditional activation of Cu ionophores by innate immune cells intensifies the hostile antimicrobial environment and represents a promising approach to combat infectious disease." @default.
- W2012196995 created "2016-06-24" @default.
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- W2012196995 date "2014-08-01" @default.
- W2012196995 modified "2023-10-14" @default.
- W2012196995 title "Exploiting Innate Immune Cell Activation of a Copper-Dependent Antimicrobial Agent during Infection" @default.
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- W2012196995 doi "https://doi.org/10.1016/j.chembiol.2014.06.009" @default.
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