Escapes Fumagillin Control in Honey Bees
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.
Vyšlo v časopise:
Escapes Fumagillin Control in Honey Bees. PLoS Pathog 9(3): e32767. doi:10.1371/journal.ppat.1003185
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1003185
Souhrn
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.
Zdroje
1. BaileyL (1953) Effect of fumagillin upon Nosema apis (Zander). Nature 171: 212–213.
2. HigesM, NozalMJ, AlvaroA, BarriosL, MeanaA, et al. (2011) The stability and effectiveness of fumagillin in controlling Nosema ceranae (Microsporidia) infection in honey bees (Apis mellifera) under laboratory and field conditions. Apidologie 42: 364–377.
3. WilliamsGR, SampsonMA, ShutlerD, RogersRE (2008) Does fumagillin control the recently detected invasive parasite Nosema ceranae in western honey bees (Apis mellifera)? J Invertebr Pathol 99: 342–344.
4. FriesI, FengF, daSilvaA, SlemendaSB, PieniazekNJ (1996) Nosema ceranae n sp (Microspora, Nosematidae), morphological and molecular characterization of a microsporidian parasite of the Asian honey bee Apis cerana (Hymenoptera, Apidae). Eur J of Protistol 32: 356–365.
5. HuangWF, JiangJH, ChenYW, WangCH (2007) A Nosema ceranae isolate from the honeybee Apis mellifera. Apidologie 38: 30–37.
6. Cox-FosterDL, ConlanS, HolmesEC, PalaciosG, EvansJD, et al. (2007) A metagenomic survey of microbes in honey bee colony collapse disorder. Science 318: 283–287.
7. BromenshenkJJ, HendersonCB, WickCH, StanfordMF, ZulichAW, et al. (2010) Iridovirus and microsporidian linked to honey bee colony decline. PLoS One 5: e13181 doi:10.1371/journal.pone.0013181
8. PajueloAG, TorresC, BermejoFJO (2008) Colony losses: a double blind trial on the influence of supplementary protein nutrition and preventative treatment with fumagillin against Nosema ceranae. J Apic Res 47: 84–86.
9. WilliamsGR, ShutlerD, LittleCM, Burgher-MacLellanKL, RogersREL (2011) The microsporidian Nosema ceranae, the antibiotic Fumagilin-B (R), and western honey bee (Apis mellifera) colony strength. Apidologie 42: 15–22.
10. LopezMI, PettisJS, SmithIB, ChuPS (2008) Multiclass determination and confirmation of antibiotic residues in honey using LC-MS/MS. J Agric Food Chem 56: 1553–1559.
11. FDA Approved Animal Drug Products Online Database System Drug Product Abstract (2012) NADA number: 009–252. Available: http://www.accessdata.fda.gov/scripts/animaldrugsatfda/report_details.cfm?dn=009-252
12. NightingaleJM, EsaiasWE, WolfeRE, NickesonJE, MaPLA (2008) Assessing honey bee equilibrium range and forage supply using satellite-derived phenology. In Proceedings of the Geoscience and Remote Sensing Symposium of the IEEE Geoscience and Remote Sensing Society 3: 763–766.
13. WebsterTC (1994) Fumagillin Affects Nosema-Apis and Honey-Bees (Hymonopterai-Apidae). J Econ Entomol 87: 601–604.
14. NozalMJ, BernalJL, MartinMT, BernalJ, AlvaroA, et al. (2008) Trace analysis of fumagillin in honey by liquid chromatography-diode array-electrospray ionization mass spectrometry. Journal of Chromatography A 1190: 224–231.
15. ChenY, EvansJD, ZhouL, BoncristianiH, KimuraK, et al. (2009) Asymmetrical coexistence of Nosema ceranae and Nosema apis in honey bees. J Invertebr Pathol 101: 204–209.
16. HuangWF, BocquetM, LeeKC, SungIH, JiangJH, et al. (2008) The comparison of rDNA spacer regions of Nosema ceranae isolates from different hosts and locations. J Invertebr Pathol 97: 9–13.
17. KleeJ, BesanaAM, GenerschE, GisderS, NanettiA, et al. (2007) Widespread dispersal of the microsporidian Nosema ceranae, an emergent pathogen of the western honey bee, Apis mellifera. J Invertebr Pathol 96: 1–10.
18. SinN, MengL, WangMQ, WenJJ, BornmannWG, et al. (1997) The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. Proc Natl Acad Sci U S A 94: 6099–6103.
19. KatinkaMD, DupratS, CornillotE, MetenierG, ThomaratF, et al. (2001) Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature 414: 450–453.
20. CornmanRS, ChenYP, SchatzMC, StreetC, ZhaoY, et al. (2009) Genomic analyses of the microsporidian Nosema ceranae, an emergent pathogen of honey bees. PLoS Pathog 5: e1000466 doi:10.1371/journal.ppat.1000466
21. AlvaradoJJ, NemkalA, SauderJM, RussellM, AkiyoshiDE, et al. (2009) Structure of a microsporidian methionine aminopeptidase type 2 complexed with fumagillin and TNP-470. Mol Biochem Parasitol 168: 158–167.
22. LefkoveB, GovindarajanB, ArbiserJL (2007) Fumagillin: an anti-infective as a parent molecule for novel angiogenesis inhibitors. Expert Rev Anti Infect Ther 5: 573–579.
23. LowtherWT, MatthewsBW (2000) Structure and function of the methionine aminopeptidases. Biochim Biophys Acta 1477: 157–167.
24. RadaV, MachovaM, HukJ, MarounekM, DuskovaD (1997) Microflora in the honeybee digestive tract: counts, characteristics and sensitivity to veterinary drugs. Apidologie 28: 357–365.
25. FallonJP, ReevesEP, KavanaghK (2011) The Aspergillus fumigatus toxin fumagillin suppresses the immune response of Galleria mellonella larvae by inhibiting the action of haemocytes. Microbiology 157: 1481–1488.
26. Schmid-HempelP, LoosliR (1998) A contribution to the knowledge of Nosema infections in bumble bees, Bombus spp. Apidologie 29: 525–535.
27. CameronSA, LozierJD, StrangeJP, KochJB, CordesN, et al. (2011) Patterns of widespread decline in North American bumble bees. Proceedings of the National Academy of Sciences of the United States of America 108: 662–667.
28. CordesN, HuangWF, StrangeJP, CameronSA, GriswoldTL, et al. (2012) Interspecific geographic distribution and variation of the pathogens Nosema bombi and Crithidia species in United States bumble bee populations. J Invertebr Pathol 109: 209–216.
29. WhittingtonR, WinstonML (2003) Effects of Nosema bombi and its treatment fumagillin on bumble bee (Bombus occidentalis) colonies. J Invertebr Pathol 84: 54–58.
30. WebsterTC, PomperKW, HuntG, ThackerEM, JonesSC (2004) Nosema apis infection in worker and queen Apis mellifera. Apidologie 35: 49–54.
31. SolterLF, MaddoxJV (1998) Microsporidia as classical biological control agents: Research and regulatory issues. Phytoprotection 79: 75–80.
32. GuindonS, GascuelO (2003) A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Systematic Biology 52: 696–704.
33. KeaneTM, CreeveyCJ, PentonyMM, NaughtonTJ, McInerneyJO (2006) Assessment of methods for amino acid matrix selection and their use on empirical data shows that ad hoc assumptions for choice of matrix are not justified. Bmc Evolutionary Biology 6: 1471–2148.
34. ForsgrenE, FriesI (2010) Comparative virulence of Nosema ceranae and Nosema apis in individual European honey bees. Vet Parasitol 3–4: 212–217.
35. PaxtonRJ, KleeJ, KorpelaS, FriesI (2007) Nosema ceranae has infected Apis mellifera in Europe since at least 1998 and may be more virulent than Nosema apis. Apidologie 38: 558–565.
36. Martin-HernandezR, MeanaA, Garcia-PalenciaP, MarinP, BotiasC, et al. (2009) Effect of temperature on the biotic potential of honeybee microsporidia. Appl Environ Microbiol 75: 2554–2557.
37. FriesI (2010) Nosema ceranae in European honey bees (Apis mellifera). J Invertebr Pathol 103 Suppl 1: S73–79.
38. HigesM, Garcia-PalenciaP, Martin-HernandezR, MeanaA (2007) Experimental infection of Apis mellifera honeybees with Nosema ceranae (Microsporidia). J Invertebr Pathol 94: 211–217.
39. LewisLC, LynchRE (1976) Influence on European corn borer (Lepidoptera:Pyralidae) of Nosema pyrausta and resistance in maize to leaf feeding. Environ Entomol 5: 139–142.
40. van FrankenhuyzenK, EblingP, McCronB, LaddT, GauthierD, et al. (2004) Occurrence of Cystosporogenes sp (Protozoa, Microsporidia) in a multi-species insect production facility and its elimination from a colony of the eastern spruce budworm, Choristoneura fumiferana (Clem.) (Lepidoptera : Tortricidae). J Invertebr Pathol 87: 16–28.
41. JohnyS, WhitmanDW, GrpBS (2008) Effect of four antimicrobials against an Encephalitozoon sp (Microsporidia) in a grasshopper host. Parasitol Int 57: 362–367.
42. LutzK, SchmittS, LinderM, HermosillaC, ZahnerH, et al. (2011) Eimeria bovis-induced modulation of the host cell proteome at the meront I stage. Mol Biochem Parasitol 175: 1–9.
43. NelsonMM, JonesAR, CarmenJC, SinaiAP, BurchmoreR, et al. (2008) Modulation of the host cell proteome by the intracellular apicomplexan parasite Toxoplasma gondii. Infect Immun 76: 828–844.
44. ZhangJF, ZhengYG, ShenYC (2007) Inhibitory effect of valienamine on the enzymatic activity of honeybee (Apis cerana Fabr.) alpha-glucosidase. Pestic Biochem Physiol 87: 73–77.
45. MayackC, NaugD (2009) Energetic stress in the honeybee Apis mellifera from Nosema ceranae infection. J Invertebr Pathol 100: 185–188.
46. WuJY, SmartMD, AnelliCM, SheppardWS (2012) Honey bees (Apis mellifera) reared in brood combs containing high levels of pesticide residues exhibit increased susceptibility to Nosema (Microsporidia) infection. J Invertebr Pathol 109: 326–329.
47. AufauvreJ, BironDG, VidauC, FontbonneR, RoudelM, et al. (2012) Parasite-insecticide interactions: a case study of Nosema ceranae and fipronil synergy on honeybee. Sci Rep 2: 326.
48. AlauxC, BrunetJL, DussaubatC, MondetF, TchamitchanS, et al. (2010) Interactions between Nosema microspores and a neonicotinoid weaken honeybees (Apis mellifera). Environ Microbiol 12: 774–782.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
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