Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity

Authors:

Elizabeth B. Smith, Stephen K. Dolan, David A. Fitzpatrick, Sean Doyle and Gary W. Jones

doi: 10.15698/mic2016.03.485
Volume 3, pp. 120 to 125, published 19/02/2016.

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Affiliations:

Department of Biology, Maynooth University, Maynooth, County Kildare, Ireland.

Keywords: 

gliotoxin, Aspergillus fumigatus, Saccharomyces cerevisiae, oxidoreductase GliT, thio-methyltransferase GtmA.

Corresponding Author(s):

Gary W. Jones, Department of Biology, Maynooth University, Maynooth, County Kildare, Ireland gary.jones@nuim.ie

Conflict of interest statement:

The authors declare no existing conflicts of interest.

Please cite this article as:

Elizabeth B. Smith, Stephen K. Dolan, David A. Fitzpatrick, Sean Doyle and Gary W. Jones (2016). Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity. Microbial Cell 3(3): 120-125. doi: 10.15698/mic2016.03.485

© 2016 Smith et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

Gliotoxin (GT) is a mycotoxin produced by some species of ascomycete fungi including the opportunistic human pathogen Aspergillus fumigatus. In order to produce GT the host organism needs to have evolved a self-protection mechanism. GT contains a redox-cycling disulfide bridge that is important in mediating toxicity. Recently is has been demonstrated that A. fumigatus possesses a novel thiomethyltransferase protein called GtmA that has the ability to thiomethylate GT in vivo, which aids the organism in regulating GT biosynthesis. It has been suggested that thiomethylation of GT and similar sulfur-containing toxins may play a role in providing self-protection in host organisms. In this work we have engineered Saccharomyces cerevisiae, a GT-naïve organism, to express A. fumigatus GtmA. We demonstrate that GtmA can readily thiomethylate GT in yeast, which results in protection of the organism from exogenous GT. Our work has implications for understanding the evolution of GT self-protection mechanisms in organisms that are GT producers and non-producers.