Within 36–48 h of a blood meal, spirochetes in the engorged tick

Within 36–48 h of a blood meal, spirochetes in the engorged tick downregulate their production of OspA and OspB, and OspC production is induced (Schwan et al., 1995; Schwan, 2003). Although there are conflicting data concerning the requirement of OspC for spirochete migration from the tick midgut to the salivary gland and also for transmission into the host (Grimm et al.,

2004; Pal et al., AZD6244 price 2004a, b; Ramamoorthi et al., 2005; Tilly et al., 2006), OspC has been shown to bind a tick salivary protein, Salp15, in vitro and in vivo, indicating a possible role for OspC in transmission and/or survival early during host colonization (Ramamoorthi et al., 2005). It is clear, however, that OspC is a B. burgdorferi virulence factor that is essential for infection in the murine host, as OspC deletion mutants are avirulent by both needle and tick infection routes (Grimm et al., Opaganib research buy 2004; Tilly et al., 2006). Furthermore, Rosa and co-workers demonstrated that most OspC mutants complemented in trans on a shuttle vector no longer contain the complementing plasmid shuttle vector 6 weeks after infection and that OspC mutants are cleared from intradermal sites of infection within 48 h postinoculation (Tilly et al., 2006). These data indicate that OspC

functions during very early stages of mouse infection and is not required for spirochete persistence. This conclusion is consistent with data from previous studies, which have shown that both ospC transcript and OspC protein levels are reduced within 2 weeks postinfection (Schwan et al., 1995; Carroll et al., 1999; Schwan & Piesman, 2000; Ohnishi

et al., 2001; Liang et al., 2002a). The mechanism of OspC function during early infection is not known, although it does not appear to involve evasion of host innate or acquired immunity, as OspC mutants are unable to infect SCID or MyD88 knockout mice (Stewart et al., 2006). Interestingly, in a recent study by Marconi and co-workers, site-directed mutagenesis of specific residues in OspC ligand-binding domain 1 (LBD1) resulted in either a loss of infectivity or affected spirochete dissemination in mice (Earnhart et al., 2010). From these data, the authors posited that the essential function of OspC in mammalian infection is to bind an unknown host-derived ligand, which may facilitate spirochete adaptation and early dissemination STK38 within the host (Earnhart et al., 2010). In addition to OspC function, the mechanisms by which OspC is regulated have been intensively studied. ospC expression is regulated by the Rrp2-RpoN-RpoS sigma factor cascade pathway and is specifically dependent upon the RpoS (sigmaS or sigma38) transcription factor (Elias et al., 2000; Hübner et al., 2001; Caimano et al., 2004; Yang et al., 2005). In response to host signals during tick feeding and mammalian infection, RpoN-dependent transcription of rpoS leads to the accumulation of rpoS transcript, and in conjunction with the small RNA DsrABb, RpoS expression is increased (Burtnick et al.

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