Targeting Fusarium graminearum control via polyamine enzyme inhibitors and polyamine analogs

Fusarium graminearum not only reduces yield and seed quality but also constitutes a risk to public or animal health owing to its ability to contaminate grains with mycotoxins. Resistance problems are emerging and control strategies based on new targets are needed. Polyamines have a key role in growth, development and differentiation. In this work, the possibility of using polyamine metabolism as a target to control F. graminearum has been assessed. It was found that putrescine induces mycotoxin production, correlating with an over expression of TRI5 and TRI6 genes. In addition, a homolog of the Saccharomyces cerevisiae TPO4 involved in putrescine excretion was up-regulated as putrescine concentration increased while DUR3 and SAM3 homologues, involved in putrescine uptake, were down-regulated. When 2.5 mM D, l-α-difluoromethylornithine (DFMO) was added to the medium, DON production decreased from 3.2 to 0.06 ng/mm(2) of colony and growth was lowered by up to 70 per cent. However, exogenous putrescine could overcome DFMO effects. Five polyamine transport inhibitors were also tested against F. graminearum. AMXT-1505 was able to completely inhibit in vitro growth and DON production. Additionally, AMXT-1505 blocked F. graminearum growth in inoculated wheat spikes reducing DON mycotoxin contamination from 76.87 μg/g to 0.62 μg/g.