Abstract B15: Fumonisins and oesophageal cancer: A proteomic and transcriptomic analyses of molecular mechanisms associated with fumonisin production by Fusarium verticillioides MRC 826 in maize

Abstract

Abstract Fusarium verticillioides is a plant pathogenic fungus that causes ear rot disease of maize and produces the carcinogenic mycotoxins, the fumonisins that are hazardous to both human and animal health. Fumonisin B1 (FB1) is the most prevalent and generally occurs at the highest levels in contaminated maize intended for human consumption. The association between fumonisin contaminated maize and maize products and human disease has raised food safety and public health concerns worldwide. Fumonisins are associated with oesophageal and liver cancer in humans and has been classified as Group 2B (potentially carcinogenic to humans) by the International Agency of the Research on Cancer. With a worldwide research focus centered on the reduction of mycotoxin exposure to humans and animals, the current study investigated the molecular mechanisms associated with fumonisin biosynthesis of the fungus in maize in order to identify potential targets for prevention. Several subcultures, showing genetic homogeneity, have been shown to produce varying amounts of the fumonisins in maize cultures. These subculture strains are therefore unique and present ideal opportunities to investigate the molecular regulatory basis of fumonisin production. Differences in gene regulation and protein expression in one high and one low fumonisin producing strain were investigated in maize cultures and in plants utilizing a susceptible maize cultivar. Quantitative real-time PCR as well as proteomic analyses were performed on maize cultures after 7, 14, 21, and 28 days, to monitor differences in the expression of the FUM genes (FUM1, FUM6, FUM8 and FUM21) as well as the total proteomic profiles. FUM1, FUM6 and FUM8 respectively showed a 5.2-, 3.1-, and 4.5-fold increase in gene expression levels in the high fumonisin producing strain, which corroborate with the higher fumonisin concentration. Expression of FUM21, one of the regulatory genes, did not differ significantly (P<0.05) between the two strains. Preliminary proteomic analyses detected a total of 729 proteins whereas 117 are unique to the high toxin producing strain and 100 unique to the low producing strain which could provide important information on differences regarding the regulation of fumonisin production. For the in planta study, the maize cobs were infected at the blister stage and harvested 10 weeks after inoculation, where after fumonisin and real-time PCR analyses were conducted Preliminary results indicated a higher virulence as well as an increase in production by the high fumonisin producing strain. This study will provide important information on the elucidation of the molecular factors involved in the regulation of fumonisin biosynthesis in maize which could identify specific targets to control fumonisin production. Citation Format: M Lilly, JF Alberts, JP Rheeder, WCA Gelderblom. Fumonisins and oesophageal cancer: A proteomic and transcriptomic analyses of molecular mechanisms associated with fumonisin production by Fusarium verticillioides MRC 826 in maize [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B15.