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Global transcriptome profile of Cryptococcus neoformans during exposure to hydrogen peroxide induced oxidative stress.

Publication ,  Journal Article
Upadhya, R; Campbell, LT; Donlin, MJ; Aurora, R; Lodge, JK
Published in: PLoS One
2013

The ability of the opportunistic fungal pathogen Cryptococcus neoformans to resist oxidative stress is one of its most important virulence related traits. To cope with the deleterious effect of cellular damage caused by the oxidative burst inside the macrophages, C. neoformans has developed multilayered redundant molecular responses to neutralize the stress, to repair the damage and to eventually grow inside the hostile environment of the phagosome. We used microarray analysis of cells treated with hydrogen peroxide (H(2)O(2)) at multiple time points in a nutrient defined medium to identify a transcriptional signature associated with oxidative stress. We discovered that the composition of the medium in which fungal cells were grown and treated had a profound effect on their capacity to degrade exogenous H(2)O(2). We determined the kinetics of H(2)O(2) breakdown by growing yeast cells under different conditions and accordingly selected an appropriate media composition and range of time points for isolating RNA for hybridization. Microarray analysis revealed a robust transient transcriptional response and the intensity of the global response was consistent with the kinetics of H(2)O(2) breakdown by treated cells. Gene ontology analysis of differentially expressed genes related to oxidation-reduction, metabolic process and protein catabolic processes identified potential roles of mitochondrial function and protein ubiquitination in oxidative stress resistance. Interestingly, the metabolic pathway adaptation of C. neoformans to H(2)O(2) treatment was remarkably distinct from the response of other fungal organisms to oxidative stress. We also identified the induction of an antifungal drug resistance response upon the treatment of C. neoformans with H(2)O(2). These results highlight the complexity of the oxidative stress response and offer possible new avenues for improving our understanding of mechanisms of oxidative stress resistance in C. neoformans.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

1

Start / End Page

e55110

Location

United States

Related Subject Headings

  • Ubiquitin
  • Transcription, Genetic
  • Oxidative Stress
  • Oligonucleotide Array Sequence Analysis
  • Mitochondria
  • Hydrogen Peroxide
  • Genomics
  • General Science & Technology
  • Gene Expression Profiling
  • Cytochrome-c Peroxidase
 

Citation

APA
Chicago
ICMJE
MLA
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Upadhya, R., Campbell, L. T., Donlin, M. J., Aurora, R., & Lodge, J. K. (2013). Global transcriptome profile of Cryptococcus neoformans during exposure to hydrogen peroxide induced oxidative stress. Plos One, 8(1), e55110. https://doi.org/10.1371/journal.pone.0055110
Upadhya, Rajendra, Leona T. Campbell, Maureen J. Donlin, Rajeev Aurora, and Jennifer K. Lodge. “Global transcriptome profile of Cryptococcus neoformans during exposure to hydrogen peroxide induced oxidative stress.Plos One 8, no. 1 (2013): e55110. https://doi.org/10.1371/journal.pone.0055110.
Upadhya R, Campbell LT, Donlin MJ, Aurora R, Lodge JK. Global transcriptome profile of Cryptococcus neoformans during exposure to hydrogen peroxide induced oxidative stress. Plos One. 2013;8(1):e55110.
Upadhya, Rajendra, et al. “Global transcriptome profile of Cryptococcus neoformans during exposure to hydrogen peroxide induced oxidative stress.Plos One, vol. 8, no. 1, 2013, p. e55110. Pubmed, doi:10.1371/journal.pone.0055110.
Upadhya R, Campbell LT, Donlin MJ, Aurora R, Lodge JK. Global transcriptome profile of Cryptococcus neoformans during exposure to hydrogen peroxide induced oxidative stress. Plos One. 2013;8(1):e55110.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

1

Start / End Page

e55110

Location

United States

Related Subject Headings

  • Ubiquitin
  • Transcription, Genetic
  • Oxidative Stress
  • Oligonucleotide Array Sequence Analysis
  • Mitochondria
  • Hydrogen Peroxide
  • Genomics
  • General Science & Technology
  • Gene Expression Profiling
  • Cytochrome-c Peroxidase