Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism
Alpha-Gal Syndrome (AGS) is an IgE-mediated delayed-type hypersensitivity reaction to the oligosaccharide galactose-α-1, 3-galactose (α-gal) injected into humans from the lone-star tick (Amblyomma americanum) bite. Indeed, α-gal is discovered in salivary glands of lone-star tick; however, the tick’s...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:d8ae8486b1e142ea8d00e070f858ab6e2021-12-01T22:17:42ZAlpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism2235-298810.3389/fcimb.2021.775371https://doaj.org/article/d8ae8486b1e142ea8d00e070f858ab6e2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.775371/fullhttps://doaj.org/toc/2235-2988Alpha-Gal Syndrome (AGS) is an IgE-mediated delayed-type hypersensitivity reaction to the oligosaccharide galactose-α-1, 3-galactose (α-gal) injected into humans from the lone-star tick (Amblyomma americanum) bite. Indeed, α-gal is discovered in salivary glands of lone-star tick; however, the tick’s specific intrinsic factors involved in endogenous α-gal production and presentation to host during hematophagy are poorly understood. This study aimed to investigate the functional role of two tick enzymes, α-D-galactosidase (ADGal) and β-1,4 galactosyltransferases (β-1,4GalT), in endogenous α-gal production, carbohydrate metabolism, and N-glycan profile in lone-star tick. The ADGal enzyme cleaves terminal α-galactose moieties from glycoproteins and glycolipids, whereas β-1,4GalT transfers α-galactose to a β1,4 terminal linkage acceptor sugars—GlcNAc, Glc, and Xyl—in various processes of glycoconjugate synthesis. An RNA interference approach was utilized to silence ADGal and β-1,4GalT in Am. americanum to examine their function in α-gal metabolism in tick and AGS onset. Silencing of ADGal led to the significant downregulation of genes involved in galactose metabolism and transport in Am. americanum. Immunoblot and N-glycan analysis of the Am. americanum salivary glands showed a significant reduction in α-gal levels in silenced tissues. However, there was no significant difference in the level of α-gal in β-1,4GalT-silenced tick salivary glands. A basophil-activation test showed a decrease in the frequency of activated basophil by ADGal-silenced salivary glands. These results provide an insight into the roles of ADGal and β-1,4GalT in α-gal production and presentation in ticks and the probable involvement in the onset of AGS.Surendra Raj SharmaGary CrispellAhmed MohamedCameron CoxJoshua LangeShailesh ChoudharyScott P. ComminsShahid KarimShahid KarimFrontiers Media S.A.articlealpha-galtickred meat allergyalpha-gal syndromealpha-D-galactosidasebeta-1MicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021) |
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alpha-gal tick red meat allergy alpha-gal syndrome alpha-D-galactosidase beta-1 Microbiology QR1-502 |
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alpha-gal tick red meat allergy alpha-gal syndrome alpha-D-galactosidase beta-1 Microbiology QR1-502 Surendra Raj Sharma Gary Crispell Ahmed Mohamed Cameron Cox Joshua Lange Shailesh Choudhary Scott P. Commins Shahid Karim Shahid Karim Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism |
| description |
Alpha-Gal Syndrome (AGS) is an IgE-mediated delayed-type hypersensitivity reaction to the oligosaccharide galactose-α-1, 3-galactose (α-gal) injected into humans from the lone-star tick (Amblyomma americanum) bite. Indeed, α-gal is discovered in salivary glands of lone-star tick; however, the tick’s specific intrinsic factors involved in endogenous α-gal production and presentation to host during hematophagy are poorly understood. This study aimed to investigate the functional role of two tick enzymes, α-D-galactosidase (ADGal) and β-1,4 galactosyltransferases (β-1,4GalT), in endogenous α-gal production, carbohydrate metabolism, and N-glycan profile in lone-star tick. The ADGal enzyme cleaves terminal α-galactose moieties from glycoproteins and glycolipids, whereas β-1,4GalT transfers α-galactose to a β1,4 terminal linkage acceptor sugars—GlcNAc, Glc, and Xyl—in various processes of glycoconjugate synthesis. An RNA interference approach was utilized to silence ADGal and β-1,4GalT in Am. americanum to examine their function in α-gal metabolism in tick and AGS onset. Silencing of ADGal led to the significant downregulation of genes involved in galactose metabolism and transport in Am. americanum. Immunoblot and N-glycan analysis of the Am. americanum salivary glands showed a significant reduction in α-gal levels in silenced tissues. However, there was no significant difference in the level of α-gal in β-1,4GalT-silenced tick salivary glands. A basophil-activation test showed a decrease in the frequency of activated basophil by ADGal-silenced salivary glands. These results provide an insight into the roles of ADGal and β-1,4GalT in α-gal production and presentation in ticks and the probable involvement in the onset of AGS. |
| format |
article |
| author |
Surendra Raj Sharma Gary Crispell Ahmed Mohamed Cameron Cox Joshua Lange Shailesh Choudhary Scott P. Commins Shahid Karim Shahid Karim |
| author_facet |
Surendra Raj Sharma Gary Crispell Ahmed Mohamed Cameron Cox Joshua Lange Shailesh Choudhary Scott P. Commins Shahid Karim Shahid Karim |
| author_sort |
Surendra Raj Sharma |
| title |
Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism |
| title_short |
Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism |
| title_full |
Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism |
| title_fullStr |
Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism |
| title_full_unstemmed |
Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism |
| title_sort |
alpha-gal syndrome: involvement of amblyomma americanum α-d-galactosidase and β-1,4 galactosyltransferase enzymes in α-gal metabolism |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/d8ae8486b1e142ea8d00e070f858ab6e |
| work_keys_str_mv |
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