Tick galactosyltransferases are involved in α-Gal synthesis and play a role during Anaplasma phagocytophilum infection and Ixodes scapularis tick vector development.

Abstract

The carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) is produced in all mammals except for humans, apes and old world monkeys that lost the ability to synthetize this carbohydrate. Therefore, humans can produce high antibody titers against α-Gal. Anti-α-Gal IgE antibodies have been associated with tick-induced allergy (i.e. α-Gal syndrome) and anti-α-Gal IgG/IgM antibodies may be involved in protection against malaria, leishmaniasis and Chagas disease. The α-Gal on tick salivary proteins plays an important role in the etiology of the α-Gal syndrome. However, whether ticks are able to produce endogenous α-Gal remains currently unknown. In this study, the Ixodes scapularis genome was searched for galactosyltransferases and three genes were identified as potentially involved in the synthesis of α-Gal. Heterologous gene expression in α-Gal-negative cells and gene knockdown in ticks confirmed that these genes were involved in α-Gal synthesis and are essential for tick feeding. Furthermore, these genes were shown to play an important role in tick-pathogen interactions. Results suggested that tick cells increased α-Gal levels in response to Anaplasma phagocytophilum infection to control bacterial infection. These results provided the molecular basis of endogenous α-Gal production in ticks and suggested that tick galactosyltransferases are involved in vector development, tick-pathogen interactions and possibly the etiology of α-Gal syndrome in humans.

• Authors: Alejandro Cabezas-Cruz, Pedro J Espinosa, Pilar Alberdi, Ladislav Šimo, James J Valdés, Lourdes Mateos-Hernández, Marinela Contreras, Margarita Villar Rayo, José de la Fuente
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 14224 (09 21 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 30242261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Arthropod Proteins
• Galactosyltransferases
• GLA protein, human
• alpha-Galactosidase

Topics

• Amino Acid Sequence
• Anaplasma phagocytophilum (pathogenicity)
• Animals
• Arthropod Proteins (metabolism)
• Cell Line, Tumor
• Disease Vectors
• Ehrlichiosis (genetics, metabolism)
• Galactosyltransferases (metabolism)
• Genome (genetics)
• HL-60 Cells
• Host-Pathogen Interactions (genetics)
• Humans
• Ixodes (microbiology)
• alpha-Galactosidase (genetics, metabolism)