An Ixodes scapularis saliva mRNA vaccine induces tick resistance and prevents Borrelia burgdorferi infection in guinea pigs.

The Lyme disease agent, Borrelia burgdorferi, colonizes the gut of the tick Ixodes scapularis, which transmits the pathogen to vertebrate hosts including humans. Here we show that B. burgdorferi colonization increases the expression of several tick gut genes including pixr, encoding a secreted gut protein with a Reeler domain. RNA interference-mediated silencing of pixr, or immunity against PIXR in mice, impairs the ability of B. burgdorferi to colonize the tick gut. PIXR inhibits bacterial biofilm formation in vitro and in vivo. Abrogation of PIXR function in vivo results in alterations in the gut microbiome, metabolome and immune responses. These alterations influence the spirochete entering the tick gut in multiple ways. PIXR abrogation also impairs larval molting, indicative of its role in tick biology. This study highlights the role of the tick gut in actively managing its microbiome, and how this impacts B. burgdorferi colonization of its arthropod vector.