Kim et al BMC Genomics (2021) 22:152 https://doi.org/10.1186/s12864-021-07429-0 RESEARCH ARTICLE Open Access Borrelia burgdorferi infection modifies protein content in saliva of Ixodes scapularis nymphs Tae Kwon Kim1,2, Lucas Tirloni1,3, Emily Bencosme-Cuevas1, Tae Heung Kim1, Jolene K Diedrich4,5, John R Yates III4 and Albert Mulenga1* Abstract Background: Lyme disease (LD) caused by Borrelia burgdorferi is the most prevalent tick-borne disease There is evidence that vaccines based on tick proteins that promote tick transmission of B burgdorferi could prevent LD As Ixodes scapularis nymph tick bites are responsible for most LD cases, this study sought to identify nymph tick saliva proteins associated with B burgdorferi transmission using LC-MS/MS Tick saliva was collected using a non-invasive method of stimulating ticks (uninfected and infected: unfed, and every 12 h during feeding through 72 h, and fullyfed) to salivate into 2% pilocarpine-PBS for protein identification using LC-MS/MS Results: We identified a combined 747 tick saliva proteins of uninfected and B burgdorferi infected ticks that were classified into 25 functional categories: housekeeping-like (48%), unknown function (18%), protease inhibitors (9%), immune-related (6%), proteases (8%), extracellular matrix (7%), and small categories that account for