Borrelia burgdorferi fitness is constrained during Peromyscus leucopus infection
The Lyme disease spirochete Borrelia burgdorferi drives a range of acute and chronic maladies in humans and other incidental hosts infected with the pathogen. However, the primary vertebrate reservoir, Peromyscus leucopus appears spared from any symptomology following infection. This has led to a common hypothesis that P. leucopus and B. burgdorferi exist symbiotically: P. leucopus restrain their immune response against the microbe and enable the enzootic cycle while B. burgdorferi avoids causing damage to the host. While aspects of this hypothesis have been tested, the exact interactions that occur between P. leucopus and B. burgdorferi during infection remain largely unknown. Here we utilized an inbred colony of P. leucopus in order to compare B. burgdorferi (B31) fitness in these rodents to 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 in contrast to our expectations, B. burgdorferi were able to reach much higher burdens in M. musculus, and that the overall kinetics of infection differed between the two rodent species. Surprisingly, we also found that P. leucopus remained infectious 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 infectivity in these hosts. These observations provide new insight into the nature of reservoir species and the B. burgdorferi enzootic cycle. Overall design: Ear punches were collected from P. leucopus following infection with B. burgdorferi strain B31 at 1 week, 2 weeks, 4 weeks, and 8 weeks post infected nymph placement and compared to ear punches collected from rodents one week following uninfected nymph placement. Ear punches were placed directly in RNA-later reagent overnight. Samples were frozen at -80C before beadbeating in QIAzol and RNA isolation with the miRNeasy kit by Qiagen with an additional RWT wash. TURBO Dnase was used to degrade DNA following isolation and samples were cleaned with RNeasy MinElute Cleanup Kit by Qiagen. Purified RNA was sent to Azenta/Genewiz for library preparation and sequencing (Illumina HiSeq 2x150bp)