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

Ref ID: 18433

Author:

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

Author address:

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

Full conference title:

Society for General Microbiology

Date: 26 March 2014

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

Abstract Number: CMM/07

Conference Year: 2012

Link to conference website: http://www.sgm.ac.uk/meetings/SGM%20Dublin%202012_Abstracts.pdf

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