burgdorferi (Fikrig et al., 1991). Therefore, a major emphasis in B. burgdorferi research has been DNA Damage inhibitor to develop a new vaccine that could be used as a safe and effective second-generation preventative against Lyme disease. As B. burgdorferi is an extracellular pathogen, and humoral immunity has been shown to be protective

against this organism, vaccine studies have revolved around identifying borrelial antigens that are (1) surface exposed, (2) conserved among different strains and genospecies of Borrelia spirochetes, and (3) produced during tick transmission and mammalian infection. Any outer surface protein that fulfills these three basic requirements is considered an excellent candidate for vaccine studies. As the surface of B. burgdorferi is the interface between the host and pathogen during infection, outer membrane proteins (OMPs) also have been implicated as important virulence factors. As a first step in identifying borrelial proteins that are surface exposed, many laboratories performed microarray analyses

to examine the global response of gene expression in B. burgdorferi after exposure to either temperature shift or cultivation within a mammalian host environment (Revel et al., 2002; Brooks et al., 2003; Ojaimi et al., 2003; Tokarz et al., 2004). The underlying assumption in these studies, which has been supported by empirical data, is that genes upregulated by temperature will correspond to genes upregulated during tick feeding and transmission to the mammalian host, while genes upregulated during cultivation MG-132 in vivo science in a mammalian host correspond to genes upregulated during mammalian infection. Using these two different environmental stimuli, numerous

genes that are upregulated during tick feeding and/or mammalian infection were identified. Among the genes observed to be upregulated by temperature- and/or mammalian-specific signals, over 50 have been shown to encode known or putative leader peptides, indicating that they may encode outer surface proteins (Revel et al., 2002; Brooks et al., 2003; Ojaimi et al., 2003; Tokarz et al., 2004). Further, many of the genes identified were observed to encode hypothetical OMPs that had not previously been characterized. Therefore, a major goal in the Lyme disease field in recent years has been to further characterize surface-exposed proteins by (1) determining their cellular location throughout the enzootic cycle of B. burgdorferi, (2) examining their overall conservation among different strains and genospecies of B. burgdorferi, and (3) assessing their ability to protect mice and nonhuman primates from experimental Lyme disease. The combined studies have led to the identification of several candidate vaccine molecules and to the identification of many virulence determinants. The enzootic life cycle of B. burgdorferi is complex and typically involves horizontal transmission between ticks of the genus Ixodes and wild rodents (Lane et al., 1991).