Morphotype-specific effector functions of Cryptococcus neoformans PUM1

Kaur, Jan Naseer; Panepinto, John C.

doi:10.1038/srep23638

Cited by 16 publications

(23 citation statements)

References 19 publications

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“…Instead, the coordination of the meiotic cycle and basidial differentiation may potentially be attributed to integrated control by a shared regulatory program that orchestrates these events. Our previous study has shown that the Pumilio family RNA binding protein Pum1 is important for the expression of the meiosis protein Dmc1 and post-meiotic sporulation ( Wang et al, 2014 ; Kaur and Panepinto, 2016 ). This suggested us to test whether Pum1 is also involved in basidial maturation.…”

Section: Resultsmentioning

confidence: 99%

Genetic basis for coordination of meiosis and sexual structure maturation in Cryptococcus neoformans

Liu

Chen

et al. 2018

eLife

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In the human fungal pathogen Cryptococcus neoformans, sex can benefit its pathogenicity through production of meiospores, which are believed to offer both physical and meiosis-created lineage advantages for its infections. Cryptococcus sporulation occurs following two parallel events, meiosis and differentiation of the basidium, the characteristic sexual structure of the basidiomycetes. However, the circuit integrating these events to ensure subsequent sporulation is unclear. Here, we show the spatiotemporal coordination of meiosis and basidial maturation by visualizing event-specific molecules in developing basidia defined by a quantitative approach. Monitoring of gene induction timing together with genetic analysis reveals co-regulation of the coordinated events by a shared regulatory program. Two RRM family regulators, Csa1 and Csa2, are crucial components that bridge meiosis and basidial maturation, further determining sporulation. We propose that the regulatory coordination of meiosis and basidial development serves as a determinant underlying the production of infectious meiospores in C. neoformans.

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Section: Resultsmentioning

confidence: 99%

Genetic basis for coordination of meiosis and sexual structure maturation in Cryptococcus neoformans

Liu

Chen

et al. 2018

eLife

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“…Yet alternative splicing has been shown to poorly influence proteome diversity and appears to be more a means to finely tune gene expression in response to environmental cues (41). In contrast, several examples of regulated alternative start sites have been described suggesting that this mechanism might represent a major means to diversify the proteome in fungi (47,48). This suggests that an important part of the proteome is still not described in this kingdom.…”

Section: Fungal Genomics: a Revolution In The Study Of Fungal Pathogensmentioning

confidence: 99%

Studying fungal pathogens of humans and fungal infections: fungal diversity and diversity of approaches

Janbon

Quintin

d’Enfert

2019

Microbes and Infection

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Seminal work by Louis Pasteur revealed the contribution of fungi-yeasts and microsporidia to agroindustry and disease in animals, respectively. More than 150 years later, the impact of fungi on human health and beyond is an ever-increasing issue, although often underestimated. Recent studies estimate that fungal infections, especially those caused by Candida, Cryptococcus and Aspergillus species, kill more than one million people annually. Indeed, these neglected infections are in general very difficult to cure and the associated mortality remains very high even when antifungal treatments exist. The development of new antifungals and diagnostic tools that are both necessary to fight fungal diseases efficiently, requires greater insights in the biology of the fungal pathogens of humans in the context of the infection, on their epidemiology, and on their

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“…reporter transcription was then inhibited by the removal of galactose through washing with and 146 resuspension in YNB with 2% dextrose with and without H2O2. Northern blot analysis was 147 performed and imaged using 5 µg of RNA as previously described (17). The hybridized 148 transcript signal was normalized to rRNA gel bands.…”

Section: Stability Assays and Northern Blot Analysismentioning

confidence: 99%

Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen Cryptococcus neoformans

Leipheimer

Bloom

Campomizzi

et al. 2019

Preprint

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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 (H2O2). Our work suggests that translational repression in response to H2O2 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 (TRR1). Our results illustrate translational suppression as a key determinant of select mRNA decay, gene expression, and subsequent survival in response to oxidative stress.ImportanceFungal 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 H2O2 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.

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Morphotype-specific effector functions of Cryptococcus neoformans PUM1

Cited by 16 publications

References 19 publications

Genetic basis for coordination of meiosis and sexual structure maturation in Cryptococcus neoformans

Genetic basis for coordination of meiosis and sexual structure maturation in Cryptococcus neoformans

Studying fungal pathogens of humans and fungal infections: fungal diversity and diversity of approaches

Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen Cryptococcus neoformans

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