Oxygen and Arsenite Synergize Phosphine Toxicity by Distinct Mechanisms

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Abstract
Phosphine is the only fumigant approved globally for general use to control insect pests in stored grain. Due to the emergence of resistance among insect pests and the lack of suitable alternative fumigants, we are investigating ways to synergistically enhance phosphine toxicity, by studying the mechanism of action of known synergists, such as oxygen, temperature, and arsenite. Under normoxia, exposure of the model organism Caenorhabditis elegans for 24h at 20 degrees C to 70ppm phosphine resulted in 10% mortality, but nearly 100% mortality if the oxygen concentration was increased to 80%. In wild-type C. elegans, toxicity of phosphine was negatively affected by a decrease in temperature to 15 degrees C and positively affected by an increase in temperature to 25 degrees C. The dld-1(wr4) strain of C. elegans is resistant to phosphine due to a mutation in the dihydrolipoamide dehydrogenase gene. It also exhibits increased mortality that is dependent on hyperoxia, when exposed to 70ppm phosphine at 20 degrees C. As with the wild-type strain, mortality decreased when exposure was carried out at 15 degrees C. At 25 degrees C, however, the strain was completely resistant to the phosphine exposure at all oxygen concentrations. Arsenite is also a synergist of phosphine toxicity, but only in the dld-1(wr4)-mutant strain. Thus, exposure to 4mM arsenite resulted in 50% mortality, which increased to 89% mortality when 70ppm phosphine and 4mM arsenite were combined. In stark contrast, 70ppm phosphine rendered 4mM arsenite nontoxic to wild-type C. elegans. These results reveal two synergists with distinct modes of action, one of which targets individuals that carry a phosphine resistance allele in the dihydrolipoamide dehydrogenase gene.
Funding Information
  • King Abdulaziz City for Science and Technology and the Saudi Arabian Cultural Mission in Australia (AU5976671445)
  • Australian Plant Biosecurity Cooperative Research Centre (PBCRC3114)

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