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This salivary pharmacopoeia enables blood-feeding while enabling pathogen transmission. High-throughput sequencing of tick salivary glands has thus become a major focus, revealing large expansion within protein encoding gene families. Among these are lipocalins, ubiquitous barrel-shaped proteins that sequester small, typically hydrophobic molecules. This study was initiated by mining the <jats:italic>Ixodes ricinus<\/jats:italic> salivary gland transcriptome for specific, uncharacterized lipocalins: three were identified. Differential expression of these <jats:italic>I. ricinus<\/jats:italic> lipocalins during feeding at distinct developmental stages and in response to <jats:italic>Borrelia afzelii<\/jats:italic> infection suggests a role in transmission of this Lyme disease spirochete. A phylogenetic analysis using 803 sequences places the three <jats:italic>I. ricinus<\/jats:italic> lipocalins with tick lipocalins that sequester monoamines, leukotrienes and fatty acids. Both structural analysis and biophysical simulations generated robust predictions showing these <jats:italic>I. ricinus<\/jats:italic> lipocalins have the potential to bind monoamines similar to other tick species previously reported. The multidisciplinary approach employed in this study characterized unique lipocalins that play a role in tick blood-feeding and transmission of the most important tick-borne pathogen in North America and Eurasia.<\/jats:p>","DOI":"10.1038\/srep32372","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T14:48:07Z","timestamp":1472741287000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Substrate prediction of Ixodes ricinus salivary lipocalins differentially expressed during Borrelia afzelii infection"],"prefix":"10.1038","volume":"6","author":[{"given":"James J.","family":"Vald\u00e9s","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Cabezas-Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radek","family":"Sima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip T.","family":"Butterill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"R\u016f\u017eek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Nuttall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,9,1]]},"reference":[{"key":"BFsrep32372_CR1","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1093\/oxfordjournals.molbev.a026224","volume":"17","author":"MD Ganfornina","year":"2000","unstructured":"Ganfornina, M. 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