For example, some lipoproteins are important for persistence in PARP inhibitor ticks, while others are important for vector to host transmission. These various functional groupings and the surface lipoproteins that fall into each group are outlined below in the following sections. Numerous surface lipoproteins have been identified that are important in colonizing and persisting within the midgut of ticks. Outer surface proteins (Osp) A and OspB were first

identified based on their antigenic properties and the observation that antibodies directed against OspA were reactive with spirochetes isolated from Lyme disease patients (Barbour et al., 1983, 1984; Howe et al., 1985). OspA and OspB are surface-exposed lipoproteins of 31 and 34 kDa, respectively (Howe et al., 1985; Fraser et al., 1997). They are co-transcribed from a single promoter and are encoded

on B. burgdorferi linear plasmid (lp) 54 (Howe et al., 1986; Barbour & Garon, 1987). OspA and OspB share a high degree of sequence and similarity (~50% sequence identity), as well as structural similarity (Bergstrom et al., 1989; Fraser et al., 1997; Li et al., 1997; Becker et al., 2005). The OspA- and OspB C-terminal regions are characterized by a positively charged cleft with an adjacent cavity that is lined with hydrophobic residues (Li et al., 1997; Becker et al., 2005), and it is thought that this cavity potentially binds an unknown ligand. The role of OspA and OspB in the infectious life cycle of B. burgdorferi has only recently been elucidated. Both OspA and OspB are expressed in the midgut of unfed ticks PS-341 clinical trial and are downregulated upon tick feeding (Schwan et al., 1995; Pal et al., 2000; Schwan & Piesman, 2000; Hefty et al., 2001, 2002b; Ohnishi et al., 2001). The abundant expression of these two lipoproteins in the tick led to the hypothesis that OspA and OspB are essential for maintenance of the spirochete within the tick environment. Correspondingly,

recombinant OspA and OspB bind tick gut extracts in vitro (Pal et al., 2000; Fikrig et al., 2004). Ribonucleotide reductase The role of OspA and OspB in the tick was further supported by in vivo examination of these proteins. In a mutant strain lacking OspA and OspB expression, mutant organisms were transmitted from infected mice to ticks and could be detected in the bloodmeal during feeding; however, the OspA/OspB mutant was unable to colonize and survive within the tick midgut (Yang et al., 2004). Interestingly, OspA alone was sufficient to restore midgut colonization to approximately 60% of wild type (Yang et al., 2004). It is now thought that OspA mediates the attachment of B. burgdorferi to the tick midgut by binding the midgut receptor TROSPA (Tick Receptor for OspA; Pal et al., 2004a). OspA is evidently downregulated for spirochetes to migrate out of the tick midgut and into the salivary glands. The role of OspB was further analyzed using a mutant strain that expresses OspA but lacks OspB.