Nosema ceranae Escapes Fumagillin Control in Honey Bees

Wei-Fone Huang,Leellen F Solter,Peter M Yau,Brian S Imai,David S Schneider

doi:10.1371/journal.ppat.1003185

Wei-Fone Huang, Leellen F Solter + Show 3 more

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https://doi.org/10.1371/journal.ppat.1003185

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Abstract

Fumagillin is the only antibiotic approved for control of nosema disease in honey bees and has been extensively used in United States apiculture for more than 50 years for control of Nosema apis. It is toxic to mammals and must be applied seasonally and with caution to avoid residues in honey. Fumagillin degrades or is diluted in hives over the foraging season, exposing bees and the microsporidia to declining concentrations of the drug. We showed that spore production by Nosema ceranae, an emerging microsporidian pathogen in honey bees, increased in response to declining fumagillin concentrations, up to 100% higher than that of infected bees that have not been exposed to fumagillin. N. apis spore production was also higher, although not significantly so. Fumagillin inhibits the enzyme methionine aminopeptidase2 (MetAP2) in eukaryotic cells and interferes with protein modifications necessary for normal cell function. We sequenced the MetAP2 gene for apid Nosema species and determined that, although susceptibility to fumagillin differs among species, there are no apparent differences in fumagillin binding sites. Protein assays of uninfected bees showed that fumagillin altered structural and metabolic proteins in honey bee midgut tissues at concentrations that do not suppress microsporidia reproduction. The microsporidia, particularly N. ceranae, are apparently released from the suppressive effects of fumagillin at concentrations that continue to impact honey bee physiology. The current application protocol for fumagillin may exacerbate N. ceranae infection rather than suppress it.

Highlights

Bicyclohexylammonium fumagillin, an antibiotic isolated from the fungus Aspergillus fumigatus, has been the only widely used treatment for nosemosis, or ‘‘nosema disease’’, in western honey bees, Apis mellifera, [1,2] for nearly 60 years [2]
A microsporidian pathogen described from Asian honey bees, was discovered infecting European honey bees coincident with early reports of Colony Collapse Disorder (CCD) and has been suggested to be a factor in honey bee declines
The only known reliable treatment for the naturally occurring Nosema apis, subsequently increased but controversial field results were reported for N. ceranae

Summary

Introduction

Bicyclohexylammonium fumagillin, an antibiotic isolated from the fungus Aspergillus fumigatus, has been the only widely used treatment for nosemosis, or ‘‘nosema disease’’, in western honey bees, Apis mellifera, [1,2] for nearly 60 years [2]. The antibiotic (hereafter ‘‘fumagillin’’), in the form of a 3% concentration for veterinary use, is considered to be the only effective treatment for Nosema apis infection and suppresses the recently discovered microsporidian pathogen, Nosema ceranae, in honey bees [3]. Since the discovery of N. ceranae, fumagillin sales have increased, and residues of the antibiotic were detected in harvested honey in the U.S [10]. Fumagillin treatment is prohibited during the foraging season [11], a time period that exceeds 6 months in most areas of the U.S [12]. Fumagillin persists inside hives [2], and degrades over time [14]

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