|REIF, KATHRYN - Washington State University|
|PALMER, GUY - Washington State University|
|CROWDER, DAVID - Washington State University|
Submitted to: PLoS Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/10/2014
Publication Date: 11/13/2014
Citation: Reif, K.E., Palmer, G.H., Crowder, D.W., Ueti, M.W., Noh, S.M. 2014. Restriction of francisella novicida genetic diversity during infection of the vector midgut. PLoS Pathogens. doi: 10.1371/journal.ppat.1004499.
Interpretive Summary: Co-infection, the presence of multiple genotypes of the same pathogen species within an infected individual, is common. Genotype diversity, defined here as the number of different genotypes, and the interaction between genotypes can strongly influence virulence and pathogen transmission. Understanding how genotypic diversity affects transmission of pathogens that naturally cycle among disparate hosts, such as vector-borne pathogens, is especially important as the capacity of the host and vector to sustain genotypic diversity may differ. To address this point, we exposed Dermacentor andersoni ticks, via infected mice, to variably diverse populations of Francisella novicida genotypes. Interestingly, we found that ticks served as greater ecological filters for genotypic diversity as compared to mice. This loss in the number of genotypes was due to both competitive suppression and exclusion. Based on these data as well as a model we determined that high numbers of ticks in an environment will support genotypic diversity, while environments with low tick numbers, genotypic diversity will be rapidly lost. Together, these results provide evidence for both the population dynamics of the vector, especially vector-to-host ratio, and competition among genotypes as important determinants for the maintenance of pathogen genotypic diversity.
Technical Abstract: The genetic diversity of pathogens and interactions between genotypes can strongly influence pathogen phenotypes, such as transmissibility and virulence. For vector-borne pathogens, both mammalian hosts and arthropod vectors may influence pathogen genotypic richness (number of circulating genotypes in an area) by preventing infection and/or transmission of particular genotypes. Mammalian hosts can act as “ecological filters” for pathogen diversity, where novel variants are often rapidly eliminated because of stochastic events or specific fitness costs. However, whether vectors can serve a similar role in limiting pathogen diversity is less clear. Here we show, using Francisella novicida and Dermacentor andersoni, a natural vector of Francisella sp. that the tick vector acts as a stronger ecological filter for pathogen diversity as compared with the mammalian host. When both mice and ticks were exposed to mixtures of F. novicida genotypes, significantly fewer genotypes co-colonized ticks compared to mice. Additionally, increased genotypic richness negatively affected the percent of available genotypes recovered from both mice and ticks. Competition among genotypes contributed to the reduction of diversity during tick colonization, as genotypes unable to colonize ticks during mixed genotype infections were competent to colonize ticks during individual genotype infection. Thus, competition among pathogen genotypes within the tick vector can greatly limit pathogen genotypic diversity. With the tick serving as a bottleneck for genotypic diversity, genotypes with decreased fitness are especially susceptible to be lost from a population. Using these results, we developed a model to further demonstrate how vector population dynamics, especially vector-to-host ratio, most greatly affected pathogen genotypic diversity in a population over time. Understanding pathogen genotype population dynamics will aid in identification of the variables that most strongly affect pathogen transmission and disease ecology.