4.7 Article

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

Journal

BIOMOLECULES
Volume 11, Issue 11, Pages -

Publisher

MDPI
DOI: 10.3390/biom11111600

Keywords

Nosema ceranae; microsporidia; proteasome; therapeutic; pollination

Funding

  1. USDA National Institute of Food and Agriculture [2019-67030-29466, 1019009]
  2. California State Beekeepers Association
  3. NIH [5R01GM118600]

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Nosema ceranae, a microsporidian parasite, is sensitive to pharmacological disruption of proteasome function, making proteasome inhibition a potential novel treatment strategy for infection in honey bees.
The microsporidia Nosema ceranae is an obligate intracellular parasite that causes honey bee mortality and contributes to colony collapse. Fumagillin is presently the only pharmacological control for N. ceranae infections in honey bees. Resistance is already emerging, and alternative controls are critically needed. Nosema spp. exhibit increased sensitivity to heat shock, a common proteotoxic stress. Thus, we hypothesized that targeting the Nosema proteasome, the major protease removing misfolded proteins, might be effective against N. ceranae infections in honey bees. Nosema 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, N. ceranae 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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