Microbiology meets chemical biology: the Aspergillus fumigatus protein GliK is involved in gliotoxin biosynthesis and self-protection

STEPHEN DOLAN, Rebecca Owens, Lorna Gallagher, Kevin Kavanagh & Sean Doyle

Author address: 

National University of Ireland Maynooth, Maynooth, Co. Kildare, Ireland

Abstract: 

Gliotoxin, a redox active molecule, is secreted by Aspergillus fumigatus and plays a significant role in mediating its virulence. Biosynthesis and secretion of this molecule is encoded by a 13 gene cluster and the function of a number of genes within this cluster is still unknown. The purpose of this work was to investigate the function of a gene, gliK, in the cluster. Gliotoxin presence or absence in an A. fumigatus strain lacking gliK (916;gliK) was determined by RP-HPLC, MALDI-ToF and LC-MS analysis. A. fumigatus 916;gliK was found to be deficient in both gliotoxin biosynthesis and secretion. A number of mutant-specific secreted metabolites, possibly biosynthetic intermediates, were detectable by RP-HPLC and LC-MS. A. fumigatus 916;gliK was shown to be highly sensitive to both exogenous gliotoxin and hydrogen peroxide. unexpectedly, addition of exogenous gliotoxin significantly relieved (p 2 O2 -induced oxidative stress in a dosedependent manner (0-10 μg/ml). Also, organic extracts derived from A. fumigatus, which contained gliotoxin, significantly inhibited (p gliK mutant growth, while the reverse was not found. Overall, our results confirm that gliK plays a key role in gliotoxin biosynthesis and self-protection, and demonstrate that gliotoxin presence protects A. fumigatus against hydrogen peroxide-induced oxidative stress
2012

abstract No: 

CMM/07

Full conference title: 

Society for General Microbiology
    • SGM 2012