Cellular and immunological mechanisms influence host-adapted phenotypes in a vector-borne microparasite

Abstract

Predicting pathogen emergence and spillover risk requires understanding the determinants of a pathogens' host range and the traits involved in host competence. While host competence is often considered a fixed species-specific trait, it may be variable if pathogens diversify across hosts. Balancing selection can lead to maintenance of pathogen polymorphisms (multiple-niche-polymorphism; MNP). The causative agent of Lyme disease, <i>Borrelia burgdorferi</i> (<i>Bb</i>), provides a model to study the evolution of host adaptation, as some <i>Bb</i> strains defined by their outer surface protein C (<i>ospC</i>) genotype, are widespread in white-footed mice and others are associated with non-rodent vertebrates (e.g. birds). To identify the mechanisms underlying potential strain × host adaptation, we infected American robins and white-footed mice, with three <i>Bb</i> strains of different <i>ospC</i> genotypes. <i>Bb</i> burdens varied by strain in a host-dependent fashion, and strain persistence in hosts largely corresponded to <i>Bb</i> survival at early infection stages and with transmission to larvae (i.e. fitness). Early survival phenotypes are associated with cell adhesion, complement evasion and/or inflammatory and antibody-mediated removal of <i>Bb,</i> suggesting directional selective pressure for host adaptation and the potential role of MNP in maintaining OspC diversity. Our findings will guide future investigations to inform eco-evolutionary models of host adaptation for microparasites.