Sulphiredoxin plays peroxiredoxin-dependent and -independent roles via the HOG signalling pathway in Cryptococcus neoformans and contributes to fungal virulence

Rajendra Upadhya, Hyelim Kim, Kwang Woo Jung, Goun Park, Woei Lam, Jennifer K. Lodge, Yong-Sun Bahn

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Mechanisms of oxidative stress resistance are crucial virulence factors for survival and proliferation of fungal pathogens within the human host. In this study we have identified and functionally characterized the role of sulphiredoxin, Srx1, in oxidative stress resistance of Cryptococcus neoformans causing fungal meningoencephalitis and regulation of peroxiredoxins, Tsa1 and Tsa3, and thioredoxins, Trx1 and Trx2. The C.neoformansHOG (High Osmolarity Glycerol response) pathway was essential for the transcriptional regulation of SRX1 under peroxide stress conditions. A gene deletion study revealed that Srx1 was required for cells to counteract peroxide stress, but not other oxidative damaging agents. HOG1 was found to be essential for the induction of adaptive response to peroxide stress with concurrent repression of ergosterol biosynthesis in an SRX1-independent manner. Consistent with this, phosphorylation of C. neoformans Hog1 was modulated by both low and high doses of exogenous hydrogen peroxide treatment. Immunoblot analysis using the C.neoformans Tsa1 specific antibody revealed that both Srx1 and Trx1 were essential for recycling of oxidized Tsa1. In addition to its role in peroxide sensing and response C.neoformansSrx1 was also found to be required for a peroxiredoxin-independent function in promoting fungicide-dependent cell swelling and growth arrest. Finally we showed the importance of C.neoformansSrx1 in fungal pathogenesis by demonstrating its requirement for full virulence using a mouse infection model.

Original languageEnglish
Pages (from-to)630-648
Number of pages19
JournalMolecular Microbiology
Volume90
Issue number3
DOIs
Publication statusPublished - 2013 Nov 1

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Peroxiredoxins
Cryptococcus neoformans
Peroxides
Virulence
Oxidative Stress
Ergosterol
Thioredoxins
Meningoencephalitis
Gene Deletion
Recycling
Virulence Factors
Osmolar Concentration
Glycerol
Hydrogen Peroxide
Phosphorylation
Survival
Antibodies
Growth
Infection

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Microbiology

Cite this

Upadhya, Rajendra ; Kim, Hyelim ; Jung, Kwang Woo ; Park, Goun ; Lam, Woei ; Lodge, Jennifer K. ; Bahn, Yong-Sun. / Sulphiredoxin plays peroxiredoxin-dependent and -independent roles via the HOG signalling pathway in Cryptococcus neoformans and contributes to fungal virulence. In: Molecular Microbiology. 2013 ; Vol. 90, No. 3. pp. 630-648.
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Sulphiredoxin plays peroxiredoxin-dependent and -independent roles via the HOG signalling pathway in Cryptococcus neoformans and contributes to fungal virulence. / Upadhya, Rajendra; Kim, Hyelim; Jung, Kwang Woo; Park, Goun; Lam, Woei; Lodge, Jennifer K.; Bahn, Yong-Sun.

In: Molecular Microbiology, Vol. 90, No. 3, 01.11.2013, p. 630-648.

Research output: Contribution to journalArticle

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