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Host complement is widely distributed throughout mammalian body fluids and can be activated immediately as part of the first line of defense against invading pathogens. The agent of Lyme disease, Borrelia burgdorferi sensu lato (s.l.), is naturally resistant to that innate immune defense system of its hosts. One resistance mechanism appears to involve binding fluid-phase regulators of complement to distinct borrelial outer surface molecules known as CRASPs (complement regulator acquiring surface proteins). Using sensitive molecular biology techniques, expression patterns of all three classes of genes encoding the CRASPs of B. burgdorferi sensu stricto (BbCRASPs) have been analyzed throughout the natural tick-mammal infection cycle. Each class shows a different expression profile in vivo and the results are summarized herein. Studies on the expression of B. burgdorferi genes using animal models of infection have advanced our knowledge on the ability of the causative agent to circumvent innate immune defenses, the contributions of CRASPs to spirochete infectivity, and the pathogenesis of Lyme disease.

Lyme borreliae naturally maintain numerous distinct DNA elements of the cp32 family, each of which carries a mono- or bicistronic erp locus. The encoded Erp proteins are surface-exposed outer membrane lipoproteins that are produced at high levels during mammalian infection but largely repressed during colonization of vector ticks. Recent studies have revealed that some Erp proteins can serve as bacterial adhesins, binding host proteins such as the complement regulator factor H and the extracellular matrix component laminin. These results suggest that Erp proteins play roles in multiple aspects of mammalian infection.

Borrelia burgdorferi produces Pfs and LuxS enzymes for breakdown of the toxic byproducts of methylation reactions, producing 4,5-dihydroxy-2,3-pentanedione (DPD), adenine, and homocysteine. DPD and its spontaneously rearranged derivatives constitute a class of bacterial pheromones named autoinducer-2 (AI-2). We describe that B. burgdorferi produces DPD during laboratory cultivation. Furthermore, addition of in vitro synthesized DPD to cultured B. burgdorferi resulted in altered expression levels of a specific set of bacterial proteins, among which is the outer surface lipoprotein VlsE. While a large number of bacteria utilize homocysteine, the other LuxS product, for synthesis of methionine as part of the activated-methyl cycle, B. burgdorferi was found to lack that ability. We propose that the main function of B. burgdorferi LuxS is to synthesize DPD and that the Lyme disease spirochete utilizes a form of DPD as a pheromone to control gene expression.