Diseases transmitted from animals to humans are the most prevalent type of emerging infectious disease threatening human health. Lyme disease, caused by the bacterium Borrelia burgdorferi, affects more people than any other arthropod-borne (carried by insects or ticks) disease in the US. However, humans cannot be infected by all B. burgdorferi strains;the infectiousness in humans is strongly correlated with the genetic sequence at the outer surface protein C (ospC) locus of the bacteria. Of the 15 OspC variants found in the Northeastern US, only 5 are represented among strains isolated from Lyme disease patients. Similarly, each feral vertebrate species transmits a unique subset of genotypically distinct strains (ospC genotypes) to feeding ticks. That is, each vertebrate species in nature acts as a unique ecological niche that is infected with, and amplifies (transmits to feeding ticks), a different subset of the 15 ospC genotypes. Thus, the abundance of each genotype, including those that are infectious to humans, are determined by the composition and relative densities of vertebrate species. However the causal role of OspC in determining the vertebrate species a strain can infect has yet to be investigated. The major aim of this proposal is to determine if the variation in ability to infect vertebrate species, including humans, among genotypes is causally related to differences in OspC sequence. We will assess the causes and public health consequences of host selectivity of genotypes by integrating across three levels of biological complexity;molecular, organismal, and population - to address fundamental questions in Lyme disease ecology and evolution. Controlling the current Lyme disease epidemic via a human vaccine appears to be many years from actualization. Reducing the abundance of human-infectious ospC genotypes is an alternative, effective, and long-term solution to diminish Lyme disease incidence. However, intervention strategies to this end require a solid understanding of the basic biology of B. burgdorferi from the molecular to the population level. The long term goal of this proposal is to determine the mechanistic causes, both molecular and ecological, that contribute to human Lyme disease risk that could aid in the design of ecological control strategies or vaccine development. In the near term, these studies will lead to a mechanistic understanding of infectivity in vertebrate species;few examples are known of a functional basis determining the range of animal hosts a pathogen species can infect. From a global disease ecology perspective, this work is relevant as within population polymorphisms maintained by host species selectivity may be a prominent feature of the ecology of many emerging infectious diseases. In the near term, these studies will furnish fundamental new insights into factors affecting the natural abundance of, and disease risk from, animal-transmitted pathogens. Lyme disease is the most prevalent insect or tick transmitted disease in the US. Yet we know little about the mechanisms that contribute to invasiveness in humans or that escalate human Lyme disease risk. The long term goal of this proposal is to determine the mechanistic causes, both molecular and ecological, that contribute to human Lyme disease risk that could aid in the design of ecological control strategies or vaccine development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI076342-04
Application #
8131135
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Breen, Joseph J
Project Start
2008-09-15
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2011
Total Cost
$346,996
Indirect Cost
Name
University of Pennsylvania
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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