scholarly journals A novel bZIP protein, Gsb1, is required for oxidative stress response, mating, and virulence in the human pathogen Cryptococcus neoformans

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Seon Ah Cheon ◽  
Eun Jung Thak ◽  
Yong-Sun Bahn ◽  
Hyun Ah Kang
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Cryptococcus Neoformans ◽  
Oxidative Stress Response ◽  
Human Pathogen ◽  
Bzip Protein

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

2019 ◽  
Author(s):  
Jay Leipheimer ◽  
Amanda L. M. Bloom ◽  
Christopher S. Campomizzi ◽  
Yana Salei ◽  
John C. Panepinto
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Cryptococcus Neoformans ◽  
Stress Responses ◽  
Carbon Starvation ◽  
Oxidative Stress Response ◽  
Initiation Factor ◽  
Mammalian Host ◽  
Cellular Stresses ◽  
Translational Suppression

AbstractCryptococcus 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.

scholarly journals A Conserved Gcn2-Gcn4 Axis Links Methionine Utilization and the Oxidative Stress Response in Cryptococcus neoformans

2021 ◽  
Vol 2 ◽  
Author(s):  
Anna K. Stovall ◽  
Corey M. Knowles ◽  
Murat C. Kalem ◽  
John C. Panepinto
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Cryptococcus Neoformans ◽  
Fungal Pathogen ◽  
Fungal Species ◽  
Oxidative Stress Response ◽  
Initiation Factor ◽  
Polysome Profiling ◽  
Response To Stress ◽  
And Oxidative Stress

The fungal pathogen Cryptococcus neoformans relies on post-transcriptional mechanisms of gene regulation to adapt to stressors it encounters in the human host, such as oxidative stress and nutrient limitation. The kinase Gcn2 regulates translation in response to stress by phosphorylating the initiation factor eIF2, and it is a crucial factor in withstanding oxidative stress in C. neoformans, and amino acid limitation in many fungal species. However, little is known about the role of Gcn2 in nitrogen limitation in C. neoformans. In this study, we demonstrate that Gcn2 is required for C. neoformans to utilize methionine as a source of nitrogen, and that the presence of methionine as a sole nitrogen source induces eIF2 phosphorylation. The stress imposed by methionine leads to an oxidative stress response at both the levels of transcription and translation, as seen through polysome profiling as well as increased abundance of select oxidative stress response transcripts. The transcription factor Gcn4 is also required for methionine utilization and oxidative stress resistance, and RT-qPCR data suggests that it regulates expression of certain transcripts in response to oxidative stress. The results of this study suggest a connection between nitrogen metabolism and oxidative stress in C. neoformans that is mediated by Gcn4, possibly indicating the presence of a compound stress response in this clinically important fungal pathogen.

scholarly journals OxyR2 Modulates OxyR1 Activity and Vibrio cholerae Oxidative Stress Response

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Hui Wang ◽  
Nawar Naseer ◽  
Yaran Chen ◽  
Anthony Y. Zhu ◽  
Xuewen Kuai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Vibrio Cholerae ◽  
Diarrheal Disease ◽  
Transcriptional Regulator ◽  
Cysteine Residue ◽  
Oxidative Stress Response ◽  
Human Pathogen ◽  
Content Type ◽  
Low Levels

ABSTRACT Bacteria have developed capacities to deal with different stresses and adapt to different environmental niches. The human pathogen Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, utilizes the transcriptional regulator OxyR to activate genes related to oxidative stress resistance, including peroxiredoxin PrxA, in response to hydrogen peroxide. In this study, we identified another OxyR homolog in V. cholerae, which we named OxyR2, and we renamed the previous OxyR OxyR1. We found that OxyR2 is required to activate its divergently transcribed gene ahpC, encoding an alkylhydroperoxide reductase, independently of H2O2. A conserved cysteine residue in OxyR2 is critical for this function. Mutation of either oxyR2 or ahpC rendered V. cholerae more resistant to H2O2. RNA sequencing analyses indicated that OxyR1-activated oxidative stress-resistant genes were highly expressed in oxyR2 mutants even in the absence of H2O2. Further genetic analyses suggest that OxyR2-activated AhpC modulates OxyR1 activity by maintaining low intracellular concentrations of H2O2. Furthermore, we showed that ΔoxyR2 and ΔahpC mutants were less fit when anaerobically grown bacteria were exposed to low levels of H2O2 or incubated in seawater. These results suggest that OxyR2 and AhpC play important roles in the V. cholerae oxidative stress response.

scholarly journals Environmental Conditions Modulate the Transcriptomic Response of Both Caulobacter crescentus Morphotypes to Cu Stress

2021 ◽  
Vol 9 (6) ◽  
pp. 1116
Author(s):  
Laurens Maertens ◽  
Pauline Cherry ◽  
Françoise Tilquin ◽  
Rob Van Houdt ◽  
Jean-Yves Matroule
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Stress Responses ◽  
Caulobacter Crescentus ◽  
Oxidative Stress Response ◽  
Transport Systems ◽  
Transcriptomic Response ◽  
Swarmer Cell ◽  
Cu Stress ◽  
Cellular Environment

Bacteria encounter elevated copper (Cu) concentrations in multiple environments, varying from mining wastes to antimicrobial applications of copper. As the role of the environment in the bacterial response to Cu ion exposure remains elusive, we used a tagRNA-seq approach to elucidate the disparate responses of two morphotypes of Caulobacter crescentus NA1000 to moderate Cu stress in a complex rich (PYE) medium and a defined poor (M2G) medium. The transcriptome was more responsive in M2G, where we observed an extensive oxidative stress response and reconfiguration of the proteome, as well as the induction of metal resistance clusters. In PYE, little evidence was found for an oxidative stress response, but several transport systems were differentially expressed, and an increased need for histidine was apparent. These results show that the Cu stress response is strongly dependent on the cellular environment. In addition, induction of the extracytoplasmic function sigma factor SigF and its regulon was shared by the Cu stress responses in both media, and its central role was confirmed by the phenotypic screening of a sigF::Tn5 mutant. In both media, stalked cells were more responsive to Cu stress than swarmer cells, and a stronger basal expression of several cell protection systems was noted, indicating that the swarmer cell is inherently more Cu resistant. Our approach also allowed for detecting several new transcription start sites, putatively indicating small regulatory RNAs, and additional levels of Cu-responsive regulation.

scholarly journals Meta-Analysis of Oxidative Transcriptomes in Insects

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 345
Author(s):  
Hidemasa Bono
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Meta Analysis ◽  
Adherens Junction ◽  
Enrichment Analysis ◽  
Oxidative Stress Response ◽  
Insect Species ◽  
Rna Seq ◽  
Manual Curation ◽  
Analysis Workflow

Data accumulation in public databases has resulted in extensive use of meta-analysis, a statistical analysis that combines the results of multiple studies. Oxidative stress occurs when there is an imbalance between free radical activity and antioxidant activity, which can be studied in insects by transcriptome analysis. This study aimed to apply a meta-analysis approach to evaluate insect oxidative transcriptomes using publicly available data. We collected oxidative stress response-related RNA sequencing (RNA-seq) data for a wide variety of insect species, mainly from public gene expression databases, by manual curation. Only RNA-seq data of Drosophila melanogaster were found and were systematically analyzed using a newly developed RNA-seq analysis workflow for species without a reference genome sequence. The results were evaluated by two metric methods to construct a reference dataset for oxidative stress response studies. Many genes were found to be downregulated under oxidative stress and related to organ system process (GO:0003008) and adherens junction organization (GO:0034332) by gene enrichment analysis. A cross-species analysis was also performed. RNA-seq data of Caenorhabditis elegans were curated, since no RNA-seq data of insect species are currently available in public databases. This method, including the workflow developed, represents a powerful tool for deciphering conserved networks in oxidative stress response.

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