Borrelta burgdorferi is the etiological agent of Lyme disease, a multisystem disorder of humans of emerging significance. Lyme disease occurs subsequent to infection with B burgdorferi via the bite of a tick. The spirochete is confronted with a significant increase in temperature during transfer from the tick to the mammalian host. Similar temperature shifts are known to influence the expression of a number of antigenic and metabolic functions in a wide variety of procaryotic and eucaryotic cells. Temperature-modulated protein synthesis also influences the expression of virulence functions in several human pathogens, and may also affect the immune response of the host. The dramatic increase in synthesis of a small number of highly conserved proteins by whole organisms or cultured cells in response to an elevated temperature, defined as the heat shock response, has been studied extensively. We recently were the first to describe a similar response in B burgdorferi. The high passage, non-pathogenic type strain of B burgdorferi, B31 has at least 5 proteins whose synthesis is affected by temperature. We have designated these proteins as heat stress protein 1-4 (HSPs 1-4) and heat labile protein (HLP 1). Heat stress protein 1 (75kda) is the major HSP and increases from approximately 1% of the total cell protein at 28oC to 12-18% of the total cell protein at 40oC after a 4 hour labeling period. Preliminary studies indicate that HSP 1 is a soluble protein also present in low-passage, pathogenic strains of B burgdorferi. The goals of this project are to: (1) to purify B burgdorferi HSP, (2) to determine a partial amino acid sequence for B burgdorferi HSP 1, (3) to determine the antigenic relatedness of HSP 1 to other B burgdorferi proteins and proteins from other cells, (4) to determine the immunological reactivity of B burgdorferi HSP 1 during natural infection and (5) to describe the effect of heat-stressed B burgdorferi and HSP 1 on experimental infections in neonatal rats.
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