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Published on: October 9, 2017
Proteasome Inhibition Is an Effective Treatment Strategy for Microsporidia Infection in Honey Bees
Emily M Huntsman1, Rachel M Cho1, Helen V Kogan1
1Biology Department, Barnard College, New York, NY 10027, USA.
Abstract:
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.
Insights
Honey bee parasite Nosema ceranae causes mortality. Targeting its proteasome with inhibitors offers a novel treatment strategy, as Nosema showed high sensitivity to proteasome disruption, unlike honey bees.
Area of Science:
- Apiculture
- Parasitology
- Molecular Biology
Background:
- Nosema ceranae, an intracellular parasite, significantly impacts honey bee health and survival.
- Current treatments like fumagillin face emerging resistance, necessitating alternative control methods.
- Nosema species are susceptible to proteotoxic stress, suggesting proteasome as a potential therapeutic target.
Purpose of the Study:
- To investigate the efficacy of targeting the Nosema proteasome as a novel treatment for Nosema ceranae infections in honey bees.
- To assess the structural characteristics of the Nosema proteasome and its susceptibility to pharmacological inhibitors.
Main Methods:
- Analysis of the Nosema genome and molecular modeling of its proteasome structure.
- Testing the sensitivity of Nosema ceranae to FDA-approved proteasome inhibitors in vitro.
- Evaluating the tolerance of honey bees to these inhibitors.
Main Results:
- The Nosema proteasome possesses a compact structure with conserved active sites receptive to inhibitors.
- Nosema ceranae demonstrated significant sensitivity to proteasome inhibition.
- Honey bees tolerated the tested doses of proteasome inhibitors well.
Conclusions:
- Proteasome inhibition represents a promising new therapeutic strategy against Nosema ceranae infections in honey bees.
- This approach offers a potential alternative to existing treatments facing resistance issues.
