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Thiol peroxidase is critical for virulence and resistance to nitric oxide and peroxide in the fungal pathogen, Cryptococcus neoformans.

Publication ,  Journal Article
Missall, TA; Pusateri, ME; Lodge, JK
Published in: Mol Microbiol
March 2004

Cryptococcus neoformans is a fungal pathogen most commonly causing meningitis in immunocompromised patients. Current therapies are inadequate, and novel antifungal targets are needed. We have identified by proteomics two thiol peroxidases that are differentially expressed at 37 degrees C, the temperature of the mammalian host. Consistent with their antioxidant role, we show that the genes encoding these thiol-specific antioxidants, TSA1 and TSA3, are transcriptionally induced when C. neoformans is exposed to hydrogen peroxide. Genome sequence analysis of C. neoformans revealed a third thiol peroxidase, TSA4. We constructed single, double and triple mutants of the thiol peroxidase genes through homologous recombination and analysed their function by comparing the growth of these mutants with that of the wild-type strain. The tsa1 Delta mutant shows sensitivity to hydrogen peroxide and t-butylhydroperoxide, as well as significant growth retardation at 25 degrees C and 38.5 degrees C. The tsa1 Delta mutant is also sensitive to NO, demonstrating a link between oxidative and nitrosative stress pathways. In two mouse models of cryptococcosis, the tsa1 Delta mutant is significantly less virulent.

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Published In

Mol Microbiol

DOI

ISSN

0950-382X

Publication Date

March 2004

Volume

51

Issue

5

Start / End Page

1447 / 1458

Location

England

Related Subject Headings

  • tert-Butylhydroperoxide
  • Virulence
  • Temperature
  • Sulfhydryl Compounds
  • Peroxidases
  • Oxidants
  • Nitric Oxide
  • Microbiology
  • Mice, Inbred CBA
  • Mice
 

Citation

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Missall, T. A., Pusateri, M. E., & Lodge, J. K. (2004). Thiol peroxidase is critical for virulence and resistance to nitric oxide and peroxide in the fungal pathogen, Cryptococcus neoformans. Mol Microbiol, 51(5), 1447–1458. https://doi.org/10.1111/j.1365-2958.2004.03921.x
Missall, Tricia Ann, Mary Ellen Pusateri, and Jennifer K. Lodge. “Thiol peroxidase is critical for virulence and resistance to nitric oxide and peroxide in the fungal pathogen, Cryptococcus neoformans.Mol Microbiol 51, no. 5 (March 2004): 1447–58. https://doi.org/10.1111/j.1365-2958.2004.03921.x.
Missall, Tricia Ann, et al. “Thiol peroxidase is critical for virulence and resistance to nitric oxide and peroxide in the fungal pathogen, Cryptococcus neoformans.Mol Microbiol, vol. 51, no. 5, Mar. 2004, pp. 1447–58. Pubmed, doi:10.1111/j.1365-2958.2004.03921.x.
Journal cover image

Published In

Mol Microbiol

DOI

ISSN

0950-382X

Publication Date

March 2004

Volume

51

Issue

5

Start / End Page

1447 / 1458

Location

England

Related Subject Headings

  • tert-Butylhydroperoxide
  • Virulence
  • Temperature
  • Sulfhydryl Compounds
  • Peroxidases
  • Oxidants
  • Nitric Oxide
  • Microbiology
  • Mice, Inbred CBA
  • Mice