HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pascon, R. C. Articles by McCusker, J. H. Search for Related Content PubMed PubMed Citation Articles by Pascon, R. C. Articles by McCusker, J. H. Agricola Articles by Pascon, R. C. Articles by McCusker, J. H.

Cryptococcus neoformans methionine synthase: expression analysis and requirement for virulence

¹ Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
² Department of Medicine, Infectious Disease Division, Duke University Medical Center, Durham, NC 27710, USA

Correspondence
John H. McCusker
mccus001{at}mc.duke.edu

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.

This article has been cited by other articles:

				J. M. Kingsbury and J. H. McCusker Threonine biosynthetic genes are essential in Cryptococcus neoformans Microbiology, September 1, 2008; 154(9): 2767 - 2775. [Abstract] [Full Text] [PDF]

				I. Nazi, A. Scott, A. Sham, L. Rossi, P. R. Williamson, J. W. Kronstad, and G. D. Wright Role of Homoserine Transacetylase as a New Target for Antifungal Agents Antimicrob. Agents Chemother., May 1, 2007; 51(5): 1731 - 1736. [Abstract] [Full Text] [PDF]

				T. A. Missall, M. E. Pusateri, M. J. Donlin, K. T. Chambers, J. A. Corbett, and J. K. Lodge Posttranslational, Translational, and Transcriptional Responses to Nitric Oxide Stress in Cryptococcus neoformans: Implications for Virulence Eukaryot. Cell, March 1, 2006; 5(3): 518 - 529. [Abstract] [Full Text] [PDF]