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Cryptococcus neoformans Ilv2p confers resistance to sulfometuron methyl and is required for survival at 37 degrees C and in vivo.

Publication ,  Journal Article
Kingsbury, JM; Yang, Z; Ganous, TM; Cox, GM; McCusker, JH
Published in: Microbiology (Reading)
May 2004

Acetolactate synthase catalyses the first common step in isoleucine and valine biosynthesis and is the target of several classes of inhibitors. The Cryptococcus neoformans ILV2 gene, encoding acetolactate synthase, was identified by complementation of a Saccharomyces cerevisiae ilv2 mutant. C. neoformans is highly resistant to the commercially available acetolactate synthase inhibitor, sulfometuron methyl (SM). Expression of C. neoformans ILV2 in S. cerevisiae conferred SM resistance, indicating that the SM resistance of C. neoformans is due, at least in part, to C. neoformans Ilv2p. The C. neoformans ILV2 gene was disrupted. The ilv2 mutants were auxotrophic for isoleucine and valine and the auxotrophy was satisfied by these amino acids only when proline, and not ammonium, was the nitrogen source, indicating nitrogen regulation of amino acid transport. ilv2 mutants rapidly lost viability at 37 degrees C and when starved for isoleucine and valine. Consistent with these phenotypes, an ilv2 mutant was avirulent and unable to survive in mice. Because C. neoformans Ilv2p is required for virulence and survival in vivo, inhibitors of branched-chain amino acid biosynthesis may make valuable antifungal agents.

Duke Scholars

Published In

Microbiology (Reading)

DOI

ISSN

1350-0872

Publication Date

May 2004

Volume

150

Issue

Pt 5

Start / End Page

1547 / 1558

Location

England

Related Subject Headings

  • Virulence
  • Temperature
  • Sulfonylurea Compounds
  • Saccharomyces cerevisiae
  • Mutation
  • Molecular Sequence Data
  • Microbiology
  • Microbial Sensitivity Tests
  • Mice
  • Humans
 

Citation

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ICMJE
MLA
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Kingsbury, J. M., Yang, Z., Ganous, T. M., Cox, G. M., & McCusker, J. H. (2004). Cryptococcus neoformans Ilv2p confers resistance to sulfometuron methyl and is required for survival at 37 degrees C and in vivo. Microbiology (Reading), 150(Pt 5), 1547–1558. https://doi.org/10.1099/mic.0.26928-0
Kingsbury, Joanne M., Zhonghui Yang, Tonya M. Ganous, Gary M. Cox, and John H. McCusker. “Cryptococcus neoformans Ilv2p confers resistance to sulfometuron methyl and is required for survival at 37 degrees C and in vivo.Microbiology (Reading) 150, no. Pt 5 (May 2004): 1547–58. https://doi.org/10.1099/mic.0.26928-0.
Kingsbury JM, Yang Z, Ganous TM, Cox GM, McCusker JH. Cryptococcus neoformans Ilv2p confers resistance to sulfometuron methyl and is required for survival at 37 degrees C and in vivo. Microbiology (Reading). 2004 May;150(Pt 5):1547–58.
Kingsbury, Joanne M., et al. “Cryptococcus neoformans Ilv2p confers resistance to sulfometuron methyl and is required for survival at 37 degrees C and in vivo.Microbiology (Reading), vol. 150, no. Pt 5, May 2004, pp. 1547–58. Pubmed, doi:10.1099/mic.0.26928-0.
Kingsbury JM, Yang Z, Ganous TM, Cox GM, McCusker JH. Cryptococcus neoformans Ilv2p confers resistance to sulfometuron methyl and is required for survival at 37 degrees C and in vivo. Microbiology (Reading). 2004 May;150(Pt 5):1547–1558.

Published In

Microbiology (Reading)

DOI

ISSN

1350-0872

Publication Date

May 2004

Volume

150

Issue

Pt 5

Start / End Page

1547 / 1558

Location

England

Related Subject Headings

  • Virulence
  • Temperature
  • Sulfonylurea Compounds
  • Saccharomyces cerevisiae
  • Mutation
  • Molecular Sequence Data
  • Microbiology
  • Microbial Sensitivity Tests
  • Mice
  • Humans