Threonine biosynthetic genes are essential in Cryptococcus neoformans.

Published

Journal Article

We identified and attempted to disrupt the Cryptococcus neoformans homoserine and/or threonine biosynthetic genes encoding aspartate kinase (HOM3), homoserine kinase (THR1) and threonine synthase (THR4); however, each gene proved recalcitrant to disruption. By replacing the endogenous promoters of HOM3 and THR1 with the copper-repressible CTR4-1 promoter, we showed that HOM3 and THR1 were essential for the growth of C. neoformans in rich media, when ammonium was the nitrogen source, or when threonine was supplied as an amino acid instead of a dipeptide. Moreover, the severity of the growth defect associated with HOM3 or THR1 repression increased with increasing incubation temperature. We believe this to be the first demonstration of threonine biosynthetic genes being essential in a fungus. The necessity of these genes for C. neoformans growth, particularly at physiologically relevant temperatures, makes threonine biosynthetic genes ideal anti-cryptococcal drug targets.

Full Text

Duke Authors

Cited Authors

  • Kingsbury, JM; McCusker, JH

Published Date

  • September 2008

Published In

Volume / Issue

  • 154 / Pt 9

Start / End Page

  • 2767 - 2775

PubMed ID

  • 18757810

Pubmed Central ID

  • 18757810

International Standard Serial Number (ISSN)

  • 1350-0872

Digital Object Identifier (DOI)

  • 10.1099/mic.0.2008/019729-0

Language

  • eng

Conference Location

  • England