The infectivity gene bbk13 is important for multiple phases of the Borrelia burgdorferi enzootic cycle

Lyme disease is a multi-stage 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. Herein, we aimed to understand the role of bbk13 in the enzootic cycle of B. burgdorferi . B. burgdorferi 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 Δ bbk13 B. burgdorferi . Despite overcoming the early barrier in the skin, Δ bbk13 B. burgdorferi remained attenuated for distal tissue colonization after tick transmission. Disseminated infection of Δ bbk13 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 to achieve productive disseminated infection.

Author Correction: Low vector competence in sylvatic mosquitoes limits Zika virus to initiate an enzootic cycle in South America

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Host-specific functional compartmentalization within the oligopeptide transporter during the Borrelia burgdorferi enzootic cycle

Borrelia burgdorferi must acquire all of its amino acids (AAs) from its arthropod vector and vertebrate host. Previously, we determined that peptide uptake via the oligopeptide (Opp) ABC transporter is essential for spirochete viability in vitro and during infection. Our prior study also suggested that B. burgdorferi employs temporal regulation in concert with structural variation of oligopeptide-binding proteins (OppAs) to meet its AA requirements in each biological niche. Herein, we evaluated the contributions to the B. burgdorferi enzootic cycle of three of the spirochete’s five OppAs (OppA1, OppA2, and OppA5). An oppA1 transposon (tn) mutant lysed in the hyperosmolar environment of the feeding tick, suggesting that OppA1 imports amino acids required for osmoprotection. The oppA2tn mutant displayed a profound defect in hematogenous dissemination in mice, yet persisted within skin while inducing only a minimal antibody response. These results, along with slightly decreased growth of the oppA2tn mutant within DMCs, suggest that OppA2 serves a minor nutritive role, while its dissemination defect points to an as yet uncharacterized signaling function. Previously, we identified a role for OppA5 in spirochete persistence within the mammalian host. We now show that the oppA5tn mutant displayed no defect during the tick phase of the cycle and could be tick-transmitted to naïve mice. Instead of working in tandem, however, OppA2 and OppA5 appear to function in a hierarchical manner; the ability of OppA5 to promote persistence relies upon the ability of OppA2 to facilitate dissemination. Structural homology models demonstrated variations within the binding pockets of OppA1, 2, and 5 indicative of different peptide repertoires. Rather than being redundant, B. burgdorferi’s multiplicity of Opp binding proteins enables host-specific functional compartmentalization during the spirochete lifecycle.

Impact of climate change on co-feeding transmission.

Tick-borne pathogen co-feeding transmission is a non-systemic transmission in the tick-host enzootic cycle, through which the host provides a bridge between co-feeding susceptible and infected ticks to facilitate pathogen transmission. Co-feeding transmission requires co-feeding of susceptible ticks in close (both spatially and temporally) proximity to other infected ticks on the bridging host; hence, the contribution of co-feeding transmission to tick-borne pathogen transmission in the tick-host enzootic cycle is highly affected by environmental conditions. This expert opinion focuses on co-feeding transmission and infestation dynamics of ticks under changing climate conditions.