Abstract
ABSTRACTLyme disease is a multistage inflammatory disease caused by the spirochete Borrelia burgdorferi transmitted through the bite of an infected Ixodes scapularis tick. We previously discovered a B. burgdorferi infectivity gene, bbk13, that facilitates mammalian infection by promoting spirochete population expansion in the skin inoculation site. Initial characterization of bbk13 was carried out using an intradermal needle inoculation model of mouse infection, which does not capture the complex interplay of the pathogen-vector-host triad of natural transmission. Here, we aimed to understand the role of bbk13 in the enzootic cycle of B. burgdorferi. B. burgdorferi spirochetes lacking bbk13 were unable to be acquired by naive larvae fed on needle-inoculated mice. Using a capsule feeding approach to restrict tick feeding activity to a defined skin site, we determined that delivery by tick bite alleviated the population expansion defect in the skin observed after needle inoculation of Δbbk13 B. burgdorferi. Despite overcoming the early barrier in the skin, Δbbk13 B. burgdorferi remained attenuated for distal tissue colonization after tick transmission. Disseminated infection by Δbbk13 B. burgdorferi was improved in needle-inoculated immunocompromised mice. Together, we established that bbk13 is crucial to the maintenance of B. burgdorferi in the enzootic cycle and that bbk13 is necessary beyond early infection in the skin, likely contributing to host immune evasion. Moreover, our data highlight the critical interplay between the pathogen, vector, and host as well as the distinct molecular genetic requirements for B. burgdorferi to survive at the pathogen-vector-host interface and achieve productive disseminated infection.
Highlights
Lyme disease is a multistage inflammatory disease caused by the spirochete Borrelia burgdorferi transmitted through the bite of an infected Ixodes scapularis tick
Using an intradermal needle inoculation model of infection, we showed that bbk13 is important for spirochete population expansion in the skin, which drives the downstream steps of disseminated infection, culminating in B. burgdorferi colonization of distal tissues [13]
Consistent with what we have shown previously [13], Dbbk13 B. burgdorferi spirochetes were found at reduced levels during blood dissemination (Fig. 1A) and in distal tissues (Fig. 1B)
Summary
Lyme disease is a multistage inflammatory disease caused by the spirochete Borrelia burgdorferi transmitted through the bite of an infected Ixodes scapularis tick. We previously discovered a B. burgdorferi infectivity gene, bbk, that facilitates mammalian infection by promoting spirochete population expansion in the skin inoculation site. Using an intradermal needle inoculation model of infection, we showed that bbk is important for spirochete population expansion in the skin, which drives the downstream steps of disseminated infection, culminating in B. burgdorferi colonization of distal tissues [13]. This work points toward a role of bbk in host immune evasion and uncovers a more complex model of bbk function in B. burgdorferi mammalian infection, emphasizing the impact of the natural tick vector on the establishment of B. burgdorferi infection as well as the distinct molecular genetic requirements for B. burgdorferi survival during early localized infection at the pathogen-vector-host interface and the establishment of productive disseminated infection of distal host tissues
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