Proteasome Inhibition Is an Effective Treatment Strategy for Microsporidia Infection in Honey Bees
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 eme...
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| Autores principales: | , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/183932dbc4134147a4fb0b97c2d36312 |
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| Sumario: | 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. |
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