Fumagillin: An Overview of Recent Scientific Advances and Their Significance for Apiculture

Abstract

Fumagillin is a potent fungal metabolite first isolated from Aspergillus fumigatus. It is widely used in apiculture and human medicine against a variety of microsporidian fungal infections. It has been the subject of research in cancer treatments by employing its angiogenesis inhibitory properties. The toxicity of fumagillin has limited its use for human applications and spurred the development of analogues using structure-activity relationships relating to its angiogenesis properties. These discoveries may hold the key to the development of alternative chemical treatments for use in apiculture. The toxicity of fumagillin to humans is important for beekeeping, because any residues remaining in hive products pose a direct risk to the consumer. The analytical methods published to date measure fumagillin and its decomposition products but overlook the dicyclohexylamine counterion of the salt form widely used in apiculture.

The effect of dicyclohexylamine and fumagillin on Nosema ceranae-infected honey bee (Apis mellifera) mortality in cage trial assays

“…Using Fumagilin-B ® or Fumidil-B ® therefore introduces not only one, but two potentially biologically active compounds to the bee hive (van den Heever et al 2014). We observed that the risk of bee mortality of N. ceranae -infected caged bees treated with DCH alone was not statistically different compared to the commercial Fumagilin-B ® for most of the study period, with the exception of days 11 and 17 (Table II).…”

“…The environmental prevalence of DCH also needs to be established in order to ascertain if this route of contamination is indeed of concern not only for beekeeping, but also for human health (van den Heever et al 2014).…”

“…DCH can therefore be expected to accumulate in wax, and also to exhibit a long half-life in this matrix, but this remains to be confirmed. The continuous usage of Fumagilin-B ® (and Fumidil-B ® ) since almost 1950 (van den Heever et al 2014). combined with its suspected prevalence and stability in wax, makes it highly likely that DCH will be present at elevated concentrations in this matrix.…”

“…A review paper (van den Heever et al 2014) recently pointed out that the commercial formulations of fumagillin contain fumagillin as a salt, with dicyclohexylamine (DCH) being the counter ion of fumagillin in this salt ( Figure 1). It is therefore important to realize that both fumagillin and DCH are present in a 1:1 stoichiometric ratio when applying either of the commercial formulations.…”

“…For a more comprehensive discussion on the toxicity of fumagillin and DCH, the reader is referred to a recent review (van den Heever et al 2014). During our previous research using N. ceranaeinfected caged bees to evaluate alternative chemotherapies for use against this parasite, we observed bee mortalities in the positive control cages being treated with Fumagilin-B ® of up to 71 % (van den heever et al 2015c).…”