About 180,000 people die from fungal meningitis each year. The leading cause of fungal meningitis is Cryptococcus neoformans (C. neoformans), a fungus that can infect the human brain.
The only antifungal drug currently available for the treatment of this disease is amphotericin B. Although amphotericin B is effective against C. neoformans, treatment of meningitis caused by this fungus is still associated with high failure rates and unexplained recurrence of infection. Through research, researchers at the Institute of Microbiology of the Chinese Academy of Sciences have identified that glucose in the brain can suppress the antifungal resistance that C. neoformans has acquired through a protein called Mig1.
The study showed that in mice, Mig1 inhibits the synthesis of ergosterol, a component of the fungal cell membrane and a target of amphotericin B. In addition, Mig1 also promotes the production of inositolphosphorylceramide, another component of the fungal cell membrane, which competes with amphotericin B for ergosterol, thereby limiting the drug's effect. The use of an inositolphosphorylceramide inhibitor in combination with amphotericin B improves the therapeutic efficacy against cryptococcal meningitis in mice.
PEARL
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