Proteasome Inhibition Is an Effective Treatment Strategy for Microsporidia Infection in Honey Bees

Abstract

The microsporidia <i>Nosema ceranae</i> is an obligate intracellular parasite that causes honey bee mortality and contributes to colony collapse. Fumagillin is presently the only pharmacological control for <i>N. ceranae</i> infections in honey bees. Resistance is already emerging, and alternative controls are critically needed. <i>Nosema</i> spp. exhibit increased sensitivity to heat shock, a common proteotoxic stress. Thus, we hypothesized that targeting the <i>Nosema</i> proteasome, the major protease removing misfolded proteins, might be effective against <i>N. ceranae</i> infections in honey bees. <i>Nosema</i> genome analysis and molecular modeling revealed an unexpectedly compact proteasome apparently lacking multiple canonical subunits, but with highly conserved proteolytic active sites expected to be receptive to FDA-approved proteasome inhibitors. Indeed, <i>N. ceranae</i> were strikingly sensitive to pharmacological disruption of proteasome function at doses that were well tolerated by honey bees. Thus, proteasome inhibition is a novel candidate treatment strategy for microsporidia infection in honey bees.