Lyme disease is the leading tick-borne bacterial disease in the world resulting in greater than 30,000 cases per year in the US alone. Lyme disease is caused by tick-bite transmission of the pathogenic spirochete Borrelia burgdorferi. An increased understanding of the molecular mechanisms that B. burgdorferi uses to survive throughout its infectious cycle is critical for the development of innovative diagnostic and therapeutic protocols to reduce the incidence of Lyme disease. One of the major difficulties blocking this effort has been genome- wide identification of the B. burgdorferi genes that are expressed in the mammalian host environment. Using in vivo expression technology (IVET) in B. burgdorferi for the first time we have identified B. burgdorferi genes that are expressed during an active mammalian infection. Identification of in vivo-expressed spirochete genes will make a significant contribution toward elucidation of genetic mechanisms of B. burgdorferi gene regulation, host-pathogen interactions and persistence in the mammalian host. B. burgdorferi outer surface proteins are candidate virulence factors as they likely contribute to host-pathogen interactions as immune evasion proteins, adhesins and/or signaling molecules and may be novel serodiagnostic markers or vaccine candidates. Moreover, there is a growing understanding that nutrient acquisition functions are critical determinants of B. burgdorferi pathogenesis and may represent novel antimicrobial targets and/or a mechanism to deliver antimicrobial compounds to the pathogen. Therefore, characteristics of the four leading candidate genes from our IVET screen include: (i) encoded on a virulence associated plasmid, (ii) encode a putative outer surface protein and/or (iii) encode an uncharacterized transport system. This proposal is directed at understanding B. burgdorferi infection mechanisms through genetic, biochemical and in vivo analyses of unique in vivo- expressed genes. Discovery of novel B. burgdorferi virulence factors will advance our knowledge of Lyme disease pathogenesis and provide new diagnostic and antimicrobial targets for the improved treatment of this emerging infectious disease.

Public Health Relevance

Lyme disease is an emerging infectious disease caused by tick-bite transmission of the pathogenic bacteria Borrelia burgdorferi. It is not well understood how B. burgdorferi causes disease. This project investigates newly identified B. burgdorferi genes that expressed during an infection. These studies will contribute to an understanding of how B. burgdorferi causes disease and will lead to the discovery of improved treatments for Lyme disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI099094-02
Application #
8666712
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Breen, Joseph J
Project Start
2013-06-01
Project End
2017-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$314,821
Indirect Cost
$89,821
Name
University of Central Florida
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
150805653
City
Orlando
State
FL
Country
United States
Zip Code
32826
Halpern, Micah D; Molins, Claudia R; Schriefer, Martin et al. (2014) Simple objective detection of human lyme disease infection using immuno-PCR and a single recombinant hybrid antigen. Clin Vaccine Immunol 21:1094-105
Ellis, Tisha Choudhury; Jain, Sunny; Linowski, Angelika K et al. (2013) In vivo expression technology identifies a novel virulence factor critical for Borrelia burgdorferi persistence in mice. PLoS Pathog 9:e1003567