Proteasome Inhibition Is an Effective Treatment Strategy for Microsporidia Infection in Honey Bees

The microsporidia <i>Nosema ceranae</i> is an obligate intracellular parasite that causes honey bee mortality and contributes to colony collapse. Fumagillin is presently the only pharmacological control for <i>N. ceranae</i> infections in honey bees. Resistance is already eme...

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Auteurs principaux:	Emily M. Huntsman, Rachel M. Cho, Helen V. Kogan, Nora K. McNamara-Bordewick, Robert J. Tomko, Jonathan W. Snow
Format:	article
Langue:	EN
Publié:	MDPI AG 2021
Sujets:	<i>Nosema ceranae</i> microsporidia proteasome therapeutic pollination Microbiology QR1-502
Accès en ligne:	https://doaj.org/article/183932dbc4134147a4fb0b97c2d36312
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spelling	oai:doaj.org-article:183932dbc4134147a4fb0b97c2d363122021-11-25T16:52:42ZProteasome Inhibition Is an Effective Treatment Strategy for Microsporidia Infection in Honey Bees10.3390/biom111116002218-273Xhttps://doaj.org/article/183932dbc4134147a4fb0b97c2d363122021-10-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1600https://doaj.org/toc/2218-273XThe microsporidia <i>Nosema ceranae</i> is an obligate intracellular parasite that causes honey bee mortality and contributes to colony collapse. Fumagillin is presently the only pharmacological control for <i>N. ceranae</i> infections in honey bees. Resistance is already emerging, and alternative controls are critically needed. <i>Nosema</i> spp. exhibit increased sensitivity to heat shock, a common proteotoxic stress. Thus, we hypothesized that targeting the <i>Nosema</i> proteasome, the major protease removing misfolded proteins, might be effective against <i>N. ceranae</i> infections in honey bees. <i>Nosema</i> 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, <i>N. ceranae</i> 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.Emily M. HuntsmanRachel M. ChoHelen V. KoganNora K. McNamara-BordewickRobert J. TomkoJonathan W. SnowMDPI AGarticle<i>Nosema ceranae</i>microsporidiaproteasometherapeuticpollinationMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1600, p 1600 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Nosema ceranae</i> microsporidia proteasome therapeutic pollination Microbiology QR1-502
spellingShingle	<i>Nosema ceranae</i> microsporidia proteasome therapeutic pollination Microbiology QR1-502 Emily M. Huntsman Rachel M. Cho Helen V. Kogan Nora K. McNamara-Bordewick Robert J. Tomko Jonathan W. Snow Proteasome Inhibition Is an Effective Treatment Strategy for Microsporidia Infection in Honey Bees
description	The microsporidia <i>Nosema ceranae</i> is an obligate intracellular parasite that causes honey bee mortality and contributes to colony collapse. Fumagillin is presently the only pharmacological control for <i>N. ceranae</i> infections in honey bees. Resistance is already emerging, and alternative controls are critically needed. <i>Nosema</i> spp. exhibit increased sensitivity to heat shock, a common proteotoxic stress. Thus, we hypothesized that targeting the <i>Nosema</i> proteasome, the major protease removing misfolded proteins, might be effective against <i>N. ceranae</i> infections in honey bees. <i>Nosema</i> 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, <i>N. ceranae</i> 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.
format	article
author	Emily M. Huntsman Rachel M. Cho Helen V. Kogan Nora K. McNamara-Bordewick Robert J. Tomko Jonathan W. Snow
author_facet	Emily M. Huntsman Rachel M. Cho Helen V. Kogan Nora K. McNamara-Bordewick Robert J. Tomko Jonathan W. Snow
author_sort	Emily M. Huntsman
title	Proteasome Inhibition Is an Effective Treatment Strategy for Microsporidia Infection in Honey Bees
title_short	Proteasome Inhibition Is an Effective Treatment Strategy for Microsporidia Infection in Honey Bees
title_full	Proteasome Inhibition Is an Effective Treatment Strategy for Microsporidia Infection in Honey Bees
title_fullStr	Proteasome Inhibition Is an Effective Treatment Strategy for Microsporidia Infection in Honey Bees
title_full_unstemmed	Proteasome Inhibition Is an Effective Treatment Strategy for Microsporidia Infection in Honey Bees
title_sort	proteasome inhibition is an effective treatment strategy for microsporidia infection in honey bees
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/183932dbc4134147a4fb0b97c2d36312
work_keys_str_mv	AT emilymhuntsman proteasomeinhibitionisaneffectivetreatmentstrategyformicrosporidiainfectioninhoneybees AT rachelmcho proteasomeinhibitionisaneffectivetreatmentstrategyformicrosporidiainfectioninhoneybees AT helenvkogan proteasomeinhibitionisaneffectivetreatmentstrategyformicrosporidiainfectioninhoneybees AT norakmcnamarabordewick proteasomeinhibitionisaneffectivetreatmentstrategyformicrosporidiainfectioninhoneybees AT robertjtomko proteasomeinhibitionisaneffectivetreatmentstrategyformicrosporidiainfectioninhoneybees AT jonathanwsnow proteasomeinhibitionisaneffectivetreatmentstrategyformicrosporidiainfectioninhoneybees
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Proteasome Inhibition Is an Effective Treatment Strategy for Microsporidia Infection in Honey Bees

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