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Cryptococcus neoformans is a pathogenic fungus responsible for life-threatening meningoencephalitis in immunocompromised individuals, but is resistant to the antifungal drug caspofungin. In this study, the authors demonstrated that strategies that target the fungus’s endoplasmic reticulum to alter cell wall and membrane composition can sensitize C. neoformans to the effects of caspofungin. They found that combining caspofungin with tunicamycin, an inhibitor of protein glycosylation in the endoplasmic reticulum, impaired the fungus’s structural integrity and proliferation, pointing to an effective approach to overcome antifungal drug resistance.

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