Host adaptation drives genetic diversity in a vector-borne disease system

Abstract

The range of hosts a pathogen can infect is a key trait, influencing human disease risk and reservoir host infection dynamics. Borrelia burgdorferi sensu stricto (Bb), an emerging zoonotic pathogen, causes Lyme disease and is widely considered a host generalist, commonly infecting mammals and birds. Yet the extent of intraspecific variation in Bb host breadth, its role in determining host competence, and potential implications for human infection remain unclear. We conducted a long-term study of Bb diversity, defined by the polymorphic ospC locus, across white-footed mice, passerine birds, and tick vectors, leveraging long-read amplicon sequencing. Our results reveal strong variation in host breadth across Bb genotypes, exposing a spectrum of genotype-specific host-adapted phenotypes. We found support for multiple niche polymorphism, maintaining Bb diversity in nature and little evidence of temporal shifts in genotype dominance, as would be expected under negative frequency-dependent selection. Passerine birds support the circulation of several human-invasive strains (HISs) in the local tick population and harbor greater Bb genotypic diversity compared with white-footed mice. Mouse-adapted Bb genotypes exhibited longer persistence in individual mice compared with nonadapted genotypes. Genotype communities infecting individual mice preferentially became dominated by mouse-adapted genotypes over time. We posit that intraspecific variation in Bb host breadth and adaptation helps maintain overall species fitness in response to transmission by a generalist vector.

Comparative reservoir competence ofPeromyscus leucopus, C57BL/6J, and C3H/HeN forBorrelia burgdorferiB31

“…Given the number of selective pressures B. burgdorferi faces across the enzootic cycle, including cycling into and out of a range of vertebrate hosts beyond P. leucopus , it’s possible that this represents a “hedged” strategy in which B. burgdorferi can infect numerous hosts to various degrees while selection ensures only that the spirochete remains at least partially infectious in the P. leucopus host. This is supported by data that the ospC genotype (Genotype A) of B31 is associated with a generalist lifestyle [46, 48]. We may have observed substantially better infection and transmission if we had infected with a strain with ospC Type K, which appears to be a B. burgdorferi clade more closely associated with P. leucopus infection [19, 46].…”

“…This is supported by data that the ospC genotype (Genotype A) of B31 is associated with a generalist lifestyle [46, 48]. We may have observed substantially better infection and transmission if we had infected with a strain with ospC Type K, which appears to be a B. burgdorferi clade more closely associated with P. leucopus infection [19, 46].…”

“…has emphasized that there are substantial differences among B. burgdorferi strains in their ability to infect ticks from C3H/HeJ mice [33], raising the possibility that other strains may be better or worse adapted to P. leucopus . In line with this, there is evidence of strain specificity within different reservoir hosts [19, 45, 46]. Screening additional B. burgdorferi strains in P. leucopus could enable identification of variable spirochete loci that associate with higher transmission.…”

Characterization and genomic analysis of the Lyme disease spirochete bacteriophage ϕBB-1

“…In natural populations, genetic variation in outer membrane lipoprotein alleles is associated with species-level adaptations [6,[8][9][10] and variation in outer membrane lipoprotein alleles across the genospecies is driven primarily by horizontal gene transfer [5,[11][12][13][14][15][16][17][18][19][20][21]. However, the mechanism(s) by which heterologous B. burgdorferi strains exchange genetic material are not well defined.…”

Characterization and genomic analysis of the Lyme disease spirochete bacteriophage ϕBB-1

“…In natural populations, genetic variation in outer membrane lipoprotein alleles is associated with species-level adaptations [6,[8][9][10] and variation in outer membrane lipoprotein alleles across the genospecies is driven primarily by horizontal gene transfer [5,[11][12][13][14][15][16][17][18][19][20][21]. However, the mechanism(s) by which heterologous B. burgdorferi strains exchange genetic material are not well defined.…”