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Cryptococcus neoformans methionine synthase: expression analysis and requirement for virulence.

Publication ,  Journal Article
Pascon, RC; Ganous, TM; Kingsbury, JM; Cox, GM; McCusker, JH
Published in: Microbiology (Reading)
September 2004

This paper describes (i) the expression profile of the methionine synthase gene (MET6) in the human pathogenic fungus Cryptococcus neoformans and (ii) the phenotypes of a C. neoformans met6 mutant. In contrast to the MET3 gene, which showed no significant change in expression in any environmental condition tested, the MET6 gene showed a substantial induction in response to methionine and a dramatic transcriptional induction in response to homocysteine. Like a met3 mutant, the met6 mutant was a methionine auxotroph. However, relative to a met3 mutant, the met6 mutant grew very slowly and was less heat-shock resistant. In contrast to a met3 mutant, the met6 mutant lost viability when starved of methionine, and it was deficient in capsule formation. Like a met3 mutant, the met6 mutant was avirulent. In contrast to a met3 mutant, the met6 mutant was hypersensitive to fluconazole and to the calcineurin inhibitors FK506 and cyclosporin A. A synergistic fungicidal effect was also found between each of these drugs and met6. The phenotypic differences between the met3 and met6 mutants may be due to the accumulation in met6 mutants of homocysteine, a toxic metabolic intermediate that inhibits sterol biosynthesis.

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Published In

Microbiology (Reading)

DOI

ISSN

1350-0872

Publication Date

September 2004

Volume

150

Issue

Pt 9

Start / End Page

3013 / 3023

Location

England

Related Subject Headings

  • Virulence Factors
  • Virulence
  • Transcription, Genetic
  • Tacrolimus
  • RNA, Messenger
  • RNA, Fungal
  • Mutation
  • Microbiology
  • Microbial Sensitivity Tests
  • Mice
 

Citation

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Chicago
ICMJE
MLA
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Pascon, R. C., Ganous, T. M., Kingsbury, J. M., Cox, G. M., & McCusker, J. H. (2004). Cryptococcus neoformans methionine synthase: expression analysis and requirement for virulence. Microbiology (Reading), 150(Pt 9), 3013–3023. https://doi.org/10.1099/mic.0.27235-0
Pascon, Renata C., Tonya M. Ganous, Joanne M. Kingsbury, Gary M. Cox, and John H. McCusker. “Cryptococcus neoformans methionine synthase: expression analysis and requirement for virulence.Microbiology (Reading) 150, no. Pt 9 (September 2004): 3013–23. https://doi.org/10.1099/mic.0.27235-0.
Pascon RC, Ganous TM, Kingsbury JM, Cox GM, McCusker JH. Cryptococcus neoformans methionine synthase: expression analysis and requirement for virulence. Microbiology (Reading). 2004 Sep;150(Pt 9):3013–23.
Pascon, Renata C., et al. “Cryptococcus neoformans methionine synthase: expression analysis and requirement for virulence.Microbiology (Reading), vol. 150, no. Pt 9, Sept. 2004, pp. 3013–23. Pubmed, doi:10.1099/mic.0.27235-0.
Pascon RC, Ganous TM, Kingsbury JM, Cox GM, McCusker JH. Cryptococcus neoformans methionine synthase: expression analysis and requirement for virulence. Microbiology (Reading). 2004 Sep;150(Pt 9):3013–3023.

Published In

Microbiology (Reading)

DOI

ISSN

1350-0872

Publication Date

September 2004

Volume

150

Issue

Pt 9

Start / End Page

3013 / 3023

Location

England

Related Subject Headings

  • Virulence Factors
  • Virulence
  • Transcription, Genetic
  • Tacrolimus
  • RNA, Messenger
  • RNA, Fungal
  • Mutation
  • Microbiology
  • Microbial Sensitivity Tests
  • Mice