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.
Highlights
As a sensitivity of microsporidia to ubiquitin–proteasome system (UPS) disruption might be expected due to their compacted genomes, we examined genes associated with the UPS in N. ceranae and found that this species has a degenerate proteasome apparently lacking multiple components observed in most eukaryotes
Components in a number of disparate microsporidia genomes, including N. ceranae, N. apis, cerevisiae, five of the seven β subunits appear to encode N-terminal propeptides that are Encephalitozoon hellem, Nematocida displodere, and Mitosporidium daphnia
With respect to the core particle (CP), all microsporidia species examined encoded at least 7 apparent α subunits and 7 apparent β subunits, consistent with other eukaryotes studied to date (Figure 1, Supplemental Table S2)
Summary
The western honey bee, Apis mellifera, provides pollination services of critical importance to humans in both agricultural and ecological settings [1]. Honey bee colonies have suffered from increased mortality in recent years that is likely caused by a complex set of interacting stresses [2]. The microsporidian species Nosema ceranae and Nosema apis can cause individual mortality in honey bees and have been implicated in colony collapse [4,5,6]. N. ceranae, which originated in the eastern honey bee, Apis cerana, was first observed in A. mellifera in the early 2000s and appears to have displaced N. apis in the western honey bee in many regions [5,6].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
