Comparative reservoir competence of Peromyscus leucopus, C57BL/6J, and C3H/HeN for Borrelia burgdorferi B31

Borrelia burgdorferi, 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 Peromyscus leucopus, is reported not to have reduced fitness following infection. While laboratory strains of Mus musculus mice have successfully been leveraged to model acute human Lyme disease, the ability for these rodents to model B. burgdorferi-P. leucopus interactions remains understudied. Here we compared infection of P. leucopus with B. burgdorferi B31 with infection of the traditional B. burgdorferi murine models-C57BL/6J and C3H/HeN Mus musculus, which develop signs of inflammation akin to human disease. We find that B. burgdorferi were able to reach much higher burdens (10- to 30-times higher) in multiple M. musculus skin sites, and that the overall dynamics of infection differed between the two rodent species. We also found that P. leucopus remained transmissive to larval Ixodes scapularis for a far shorter period than either M. musculus strain. In line with these observations, we found that P. leucopus does launch a modest but sustained inflammatory response against B. burgdorferi 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 P. leucopus hearts. These observations provide new insight into reservoir species and the B. burgdorferi enzootic cycle. ### Competing Interest Statement The authors have declared no competing interest.