Prolyl-tRNA synthetase inhibition reduces microsporidia infection intensity in honey bees

Abstract

Nosema ceranae is a microsporidian parasite that is pathogenic to honey bees, causing disease at the individual and colony level. N. ceranae infection can be controlled by treatment with Fumagillin, but as this the future of this drug is uncertain, alternative treatment strategies are critical. Genomic examination of proteostasis pathways in N. ceranae and its host, Apis mellifera, has revealed key differences in component conservation. One example is the amino acid response (AAR), which responds to amino acid limitation through the sensing of uncharged tRNA molecules. The AAR is conserved in the honey bee, but not in N. ceranae. Pharmacological inhibition of prolyl-tRNA synthetase activity resulted in a substantial reduction in N. ceranae infection intensity. Evident toxicity to bees suggests further work is required to make this approach safe and feasible. However, these results provide proof of principle that tRNA synthetase inhibition could be an effective future treatment strategy.