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• W2968077682 abstract "Abstract Cryptococcus neoformans is one of the few environmental fungi that can survive within a mammalian host and cause disease. Although many of the factors responsible for establishing virulence have been recognized, how they are expressed in response to certain host derived cellular stresses is rarely addressed. Here we characterize the temporal translational response of C. neoformans to oxidative stress. We find that translation is largely inhibited through the phosphorylation of the critical initiation factor elF2α by a sole kinase. Preventing elF2α mediated translational suppression resulted in growth sensitivity to hydrogen peroxide (H 2 O 2 ). Our work suggests that translational repression in response to H 2 O 2 partly facilitates oxidative stress adaptation by accelerating the decay of abundant non-stress related transcripts while facilitating the proper expression of critical oxidative stress response factors. Carbon starvation, which seems to induce translational suppression that is independent elF2α, partly restored transcript decay and the expression of the critical oxidative stress response transcript Thioredoxin Reductase 1 (T RR1 ). Our results illustrate translational suppression as a key determinant of select mRNA decay, gene expression, and subsequent survival in response to oxidative stress. Importance Fungal survival in a mammalian host requires the coordinated expression and downregulation of a large cohort of genes in response to cellular stresses. Initial infection with C. neoformans occurs at the lungs, where it interacts with host macrophages. Surviving macrophage derived cellular stresses, such as the production of reactive oxygen and nitrogen species, is believed to promote dissemination into the central nervous system. Therefore, investigating how an oxidative stress resistant phenotype is brought about in C. neoformans furthers our understanding of not only fungal pathogenesis but also unveils mechanisms of stress induced gene reprogramming. We discovered that H 2 O 2 derived oxidative stress resulted in severe translational suppression and that this suppression was necessary for the accelerated decay and expression of tested transcripts. Surprisingly, compounding oxidative stress with carbon starvation resulted in a decrease in peroxide mediated killing, revealing unexpected synergy between stress responses." @default.
• W2968077682 created "2019-08-22" @default.
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• W2968077682 date "2019-08-15" @default.
• W2968077682 modified "2023-09-26" @default.
• W2968077682 title "Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen Cryptococcus neoformans" @default.
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• W2968077682 doi "https://doi.org/10.1101/735225" @default.
• W2968077682 hasPublicationYear "2019" @default.
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