Comparative reservoir competence of , C57BL/6J, and C3H/HeN for B31.

, a Lyme disease spirochete, causes a range of acute and chronic maladies in humans. However, a primary vertebrate reservoir in the United States, the white-footed deermouse , is reported not to have reduced fitness following infection. Although laboratory strains of mice have successfully been leveraged to model acute human Lyme disease, the ability of these rodents to model interactions remains understudied. Here, we compared infection of with B31 with infection of the traditional murine models-C57BL/6J and C3H/HeN , which develop signs of inflammation akin to human disease. We find that was able to reach much higher burdens (10- to 30-times higher) in multiple skin sites and that the overall dynamics of infection differed between the two rodent species. We also found that remained transmissive to larval for a far shorter period than either strain. In line with these observations, we found that does launch a modest but sustained inflammatory response against in the skin, which we hypothesize leads to reduced bacterial viability and rodent-to-tick transmission in these hosts. Similarly, we also observe evidence of inflammation in infected hearts. These observations provide new insight into reservoir species and the enzootic cycle.IMPORTANCEA Lyme disease-causing bacteria, , must alternate between infecting a vertebrate host-usually rodents or birds-and ticks. In order to be successful in that endeavor, the bacteria must avoid being killed by the vertebrate host before it can infect a new larval tick. In this work, we examine how and one of its primary vertebrate reservoirs, , interact during an experimental infection. We find that appears to colonize its natural host less successfully than conventional laboratory mouse models, which aligns with a sustained seemingly anti-bacterial response by against the microbe. These data enhance our understanding of host-pathogen interactions and could potentially serve as a foundation to uncover ways to disrupt the spread of in nature.