Our broad objective is to understand the means by which Borrelia burgdorferi establishes an infection:transmission cycle between the tick vector and mammalian reservoir host, both of which are needed to maintain the spirochete in nature. The following research efforts relate to this goal. l. Outer surface protein variation. The outer membrane of B. burgdorferi contains several abundant proteins (Osps) that are variable in size and expression and of unknown function. It is likely that the different Osps confer distinct properties on the spirochete that are pertinent to the disparate environments in which it must survive. Rosa and Hogan have identified homologous recombination between DSP genes in natural populations of B. burgdorferi in ticks. Dr. Margolis has also determine that transcriptional regulation or mRNA stability is responsible for different patterns of Osp synthesis among clonal variants. He has cloned an osp gene that is variably expressed in B. burgdorferi in culture and is investigating the sequences and factors involved in the regulation of its expression. 2. Linear plasmid replication. An understanding of the unusual linear structure of the Borrelia chromosome and plasmids is of intrinsic interest and practical merit. Dr. Tilly has isolated homologs of heat shock genes that are involved in plasmid replication in other systems. These genes are induced by a temperature upshift as would be experienced upon transfer from a tick to a mammal. She has isolated and sequenced the gene of the Borrelia IHF homolog, another candidate gene that may be involved in linear plasmid replication, and is characterizing its biological activities in E. coli. She has identified unique concatemeric or circular forms of the linear plasmids that could represent replication intermediates.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000549-05
Application #
3768835
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Tilly, K; Elias, A F; Errett, J et al. (2001) Genetics and regulation of chitobiose utilization in Borrelia burgdorferi. J Bacteriol 183:5544-53
Eggers, C H; Kimmel, B J; Bono, J L et al. (2001) Transduction by phiBB-1, a bacteriophage of Borrelia burgdorferi. J Bacteriol 183:4771-8
Chaconas, G; Stewart, P E; Tilly, K et al. (2001) Telomere resolution in the Lyme disease spirochete. EMBO J 20:3229-37
Stewart, P E; Thalken, R; Bono, J L et al. (2001) Isolation of a circular plasmid region sufficient for autonomous replication and transformation of infectious Borrelia burgdorferi. Mol Microbiol 39:714-21
Thomas, V; Anguita, J; Samanta, S et al. (2001) Dissociation of infectivity and pathogenicity in Borrelia burgdorferi. Infect Immun 69:3507-9
Konkel, M E; Tilly, K (2000) Temperature-regulated expression of bacterial virulence genes. Microbes Infect 2:157-66
Bono, J L; Elias, A F; Kupko 3rd, J J et al. (2000) Efficient targeted mutagenesis in Borrelia burgdorferi. J Bacteriol 182:2445-52
Motaleb, M A; Corum, L; Bono, J L et al. (2000) Borrelia burgdorferi periplasmic flagella have both skeletal and motility functions. Proc Natl Acad Sci U S A 97:10899-904
Elias, A F; Bono, J L; Carroll, J A et al. (2000) Altered stationary-phase response in a Borrelia burgdorferi rpoS mutant. J Bacteriol 182:2909-18
Tilly, K; Elias, A F; Bono, J L et al. (2000) DNA exchange and insertional inactivation in spirochetes. J Mol Microbiol Biotechnol 2:433-42

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