REGULATION OF LIPOPROTEIN GENE EXPRESSION IN B BURGDORFERI : LYME DISEASE

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Objectives and Background The objective of this research is to increase our understanding of the mechanisms that regulate the expression of B. burgdorferi lipoproteins, a type of molecule that plays a key role in Lyme disease pathogenesis. We have already described the transcriptionally regulated differential levels of expression of two lipoproteins of Borrelia burgdorferi, P35 and P7.5, during growth of the spirochetes in culture from logarithmic phase to stationary phase (K. J. Indest, R. Ramamoorthy, M. Sole 4, R. D. Gilmore, B. J. B. Johnson, and M. T. Philipp, Infect. Immun. 65:1165?1171, 1997). Results We further assessed this phenomenon by investigating whether the expression of other antigens of B. burgdorferi, including some well-characterized ones, are also regulated in a growth-phase-dependent manner in vitro. These studies revealed 13 additional antigens, including OspC, BmpD, and GroEL, that were upregulated 2- to 66-fold and a 28-kDa protein that was downregulated 2- to 10-fold, during the interval between the logarithmic- and stationary-growth phases. Unlike with these in vitro-regulated proteins, the levels of expression of OspA, OspB, P72, flagellin, and BmpA remained unchanged throughout growth of the spirochetes in culture. Furthermore, ospAB, bmpAB, groEL, and fla all exhibited similar mRNA profiles, which is consistent with the constitutive expression of these genes. By contrast, the mRNA and protein profiles of ospC and bmpD indicated regulated expression of these genes. While bmpD exhibited a spike in mRNA expression in early stationary phase, ospC maintained a relatively higher level of mRNA throughout culture. These findings demonstrate that there are additional genes besides P7.5 and P35 whose regulated expression can be investigated in vitro and which may thus serve as models to facilitate the study of regulatory mechanisms in an organism that cycles between an arthropod and a vertebrate host. Future directions To further assess mechanisms of regulation of lipoprotein gene expression. FUNDING Base grant and NIH-NIAID F32 AI09980 PUBLICATIONS Ramamoorthy, R. and Philipp, M.T. 1998. Differential expression of Borrelia burgdorferi proteins during growth in vitro . Infection and Immunity. 66 5119?5124.