Abstract
BackgroundVirulence acquisition and loss is a dynamic adaptation of pathogens to thrive in changing milieus. We investigated the mechanisms of virulence loss at the whole genome level using Babesia bovis as a model apicomplexan in which genetically related attenuated parasites can be reliably derived from virulent parental strains in the natural host. We expected virulence loss to be accompanied by consistent changes at the gene level, and that such changes would be shared among attenuated parasites of diverse geographic and genetic background.ResultsSurprisingly, while single nucleotide polymorphisms in 14 genes distinguished all attenuated parasites from their virulent parental strains, all non-synonymous changes resulted in no deleterious amino acid modification that could consistently be associated with attenuation (or virulence) in this hemoparasite. Interestingly, however, attenuation significantly reduced the overall population's genome diversity with 81% of base pairs shared among attenuated strains, compared to only 60% of base pairs common among virulent parental parasites. There were significantly fewer genes that were unique to their geographical origins among the attenuated parasites, resulting in a simplified population structure among the attenuated strains.ConclusionsThis simplified structure includes reduced diversity of the variant erythrocyte surface 1 (ves) multigene family repertoire among attenuated parasites when compared to virulent parental strains, possibly suggesting that overall variance in large protein families such as Variant Erythrocyte Surface Antigens has a critical role in expression of the virulence phenotype. In addition, the results suggest that virulence (or attenuation) mechanisms may not be shared among all populations of parasites at the gene level, but instead may reflect expansion or contraction of the population structure in response to shifting milieus.
Highlights
Virulence acquisition and loss is a dynamic adaptation of pathogens to thrive in changing milieus
With increased emphasis on development and delivery of attenuated vaccines for hemoparasites such as Babesia, Theileria, and Plasmodium spp. [7,8,9], the ability to predictably and stably attenuate these pathogens would be a significant step toward vaccine implementation
We investigated a natural host-apicomplexan pathogen interaction, infection of cattle with Babesia bovis, to investigate virulence loss at the genome level using multiple strains of diverse geographical origin and genetic background
Summary
Virulence acquisition and loss is a dynamic adaptation of pathogens to thrive in changing milieus. We investigated the mechanisms of virulence loss at the whole genome level using Babesia bovis as a model apicomplexan in which genetically related attenuated parasites can be reliably derived from virulent parental strains in the natural host. As few environments are themselves stable, pathogen adaptation is a dynamic and continuous process This principle applies to virulence in which acquisition and loss of virulence is dynamic within a pathogen population, varying with host genetics, host immune status at the individual and population levels, hemoparasites such as Babesia, Theileria, and Plasmodium spp. We investigated a natural host-apicomplexan pathogen interaction, infection of cattle with Babesia bovis, to investigate virulence loss at the genome level using multiple strains of diverse geographical origin and genetic background. Attenuated vaccine generated from strains isolated in Australia confer cross protection in cattle in Africa, Latin America and Southeast Asia [11,13], suggesting that immunogens are shared between geographically divergent strains
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