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Enzymes that counteract nitrosative stress promote fungal virulence.

Publication ,  Journal Article
de Jesús-Berríos, M; Liu, L; Nussbaum, JC; Cox, GM; Stamler, JS; Heitman, J
Published in: Curr Biol
November 11, 2003

Enzymes that protect cells from reactive oxygen species (superoxide dismutase, catalase, peroxidase) have well-established roles in mammalian biology and microbial pathogenesis. Two recently identified enzymes detoxify nitric oxide (NO)-related molecules; flavohemoglobin denitrosylase consumes NO, and S-nitrosoglutathione (GSNO) reductase metabolizes GSNO. Although both enzymes protect microorganisms from nitrosative challenge in vitro, their relevance has not been established in physiological contexts. Here we studied their biological functions in Cryptococcus neoformans, an established human fungal pathogen that replicates in macrophages and whose growth in vitro and in infected animals is controlled by NO bioactivity. We show that both flavohemoglobin denitrosylase and GSNO reductase contribute to C. neoformans pathogenesis. FHB1 and GNO1 mutations abolished NO- and GSNO-consuming activity, respectively. Growth of fhb1 mutant cells was inhibited by nitrosative challenge, whereas that of gno1 mutants was not. fhb1 mutants showed attenuated virulence in a murine model, and virulence was restored in iNOS(-/-) animals. Survival of the fhb1 mutant was also reduced in activated macrophages and restored to wild-type by inhibition of NOS activity. Combining mutations in flavohemoglobin and GSNO reductase, or flavohemoglobin and superoxide dismutase, further attenuated virulence. These studies illustrate that fungal pathogens elaborate enzymatic defenses against nitrosative stress mounted by the host.

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Published In

Curr Biol

DOI

ISSN

0960-9822

Publication Date

November 11, 2003

Volume

13

Issue

22

Start / End Page

1963 / 1968

Location

England

Related Subject Headings

  • Superoxide Dismutase
  • Oxygenases
  • Nitro Compounds
  • Nitric Oxide
  • Mice, Mutant Strains
  • Mice
  • Macrophages
  • Hemeproteins
  • Glutathione
  • Developmental Biology
 

Citation

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ICMJE
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de Jesús-Berríos, M., Liu, L., Nussbaum, J. C., Cox, G. M., Stamler, J. S., & Heitman, J. (2003). Enzymes that counteract nitrosative stress promote fungal virulence. Curr Biol, 13(22), 1963–1968. https://doi.org/10.1016/j.cub.2003.10.029
Jesús-Berríos, Marisol de, Limin Liu, Jesse C. Nussbaum, Gary M. Cox, Jonathan S. Stamler, and Joseph Heitman. “Enzymes that counteract nitrosative stress promote fungal virulence.Curr Biol 13, no. 22 (November 11, 2003): 1963–68. https://doi.org/10.1016/j.cub.2003.10.029.
de Jesús-Berríos M, Liu L, Nussbaum JC, Cox GM, Stamler JS, Heitman J. Enzymes that counteract nitrosative stress promote fungal virulence. Curr Biol. 2003 Nov 11;13(22):1963–8.
de Jesús-Berríos, Marisol, et al. “Enzymes that counteract nitrosative stress promote fungal virulence.Curr Biol, vol. 13, no. 22, Nov. 2003, pp. 1963–68. Pubmed, doi:10.1016/j.cub.2003.10.029.
de Jesús-Berríos M, Liu L, Nussbaum JC, Cox GM, Stamler JS, Heitman J. Enzymes that counteract nitrosative stress promote fungal virulence. Curr Biol. 2003 Nov 11;13(22):1963–1968.
Journal cover image

Published In

Curr Biol

DOI

ISSN

0960-9822

Publication Date

November 11, 2003

Volume

13

Issue

22

Start / End Page

1963 / 1968

Location

England

Related Subject Headings

  • Superoxide Dismutase
  • Oxygenases
  • Nitro Compounds
  • Nitric Oxide
  • Mice, Mutant Strains
  • Mice
  • Macrophages
  • Hemeproteins
  • Glutathione
  • Developmental Biology