The MET5 homologue is required for growth, mating, and virulence in Cryptococcus neoformans
Date Issued
2009
Date
2009
Author(s)
Lu, Jia-Zheng
Abstract
Sulfur-containing amino acids such as cysteine and methionine are important forellular physiology. Sulfate assimilation pathway (SAP) is a reduction sequencenvolved in the biosynthesis of these amino acids from the inorganic oxidized sulfurource. In Fungi, sequential steps of SAP are similar, and enzymes involved in thisathway are also highly conserved. In Saccharomyces cerevisiae, exogenous sulfate isransported from the environment into yeast cells by sulfate transporter, Sul1p andul2p, and catalyzed by ATP sulfurylase, Met3p, to form 5’-adenylylsulfate (APS).PS is subsequently phosphorylated by Met14p, APS kinase, to produce 3’-phospho-’-adenylylsulfate (PAPS), and then reduced by Met16p (PAPS reductase) to generateulfite. Finally, the sulfite reductase enzyme complex consisted of α subunit Met10pnd β subunit Met5p further reduces sulfite to sulfide. The reduced sulfur ion can thene incorporated into sulfur-containing amino acids or compounds. In this report, wetudy the roles of the MET5 homologue in the human fungal pathogen Cryptococcuseoformans. The gene disruption construct was created by in vitro transposition andelivered into the wild-type strain by biolistic transformation. Gene disrupted mutantsere verified and characterized. C. neoformans met5 mutants were auxotrophic forysteine, reduced the growth rate, severely attenuated for mating differentiation, failedo produce melanin in vitro, and lost virulence in the alternative insect host model. Allhe defects were reverted to the wild-type by reintroduction of the intact copy MET5ene. Consistent with previous reports, our results showed that the components of SAPlay important roles in the physiological processes of C. neoformans and maybe serves potential targets for antifungal therapy.
Subjects
Sulfate assimilation pathway
Cryptococcus neoformans
Cysteine
Methionine
Saccharomyces cerevisiae
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