Regulation of ACT expression by VPS41 in response to nitrogen starvation in Cryptococcus neoformans

Di Ye, Wei Wei Li and Xiaoguan

Abstract

Cryptococcus neoformans is an important opportunistic human fungal pathogen infecting immunocompromised patients and commonly causes life-threatening cryptococcal meningitis. Previous studies have shown that the VPS41 gene plays an essential role in the starvation response, macrophage survival and pathogenicity of C. neoformans. Here we present evidence that expression of an acetyltransferase encoding gene (ACT) under nitrogen starvation conditions was stimulated by VPS41. The transcript level of ACT in the VPS41 deletion mutant vps41Δ was decreased 2.5-fold compared with that in the wild type H99, while reintroduction of the functional VPS41 gene into the vps41Δ cells drastically increased ACT expression. Moreover, constitutive expression of ACT in mutant vps41Δ resulted in greatly improved survival of recombinant strain vps41Δ::ACT under nitrogen deprivation conditions. The above observations strongly suggest that one function of VPS41 in the starvation signaling pathway is to promote ACT expression in response to nitrogen starvation. Better Understanding of the mechanism of the VPS41-mediated starvation response pathway could reveal novel drug targets for designing effective therapy for treating C. neoformans infection.