Pathogens such as Candida albicans, Neisseria meningiditis, and Streptococcus pneumonia have been shown to bind host FH, and that FH binding in N. gonorrhea and B. burgdorferi provides protection against complement killing in vitro. BbCRASPs have been identified according to their ability to bind proteins of the FH family, although individual BbCRASPs vary in their affinities for particular FH family proteins. For example, only BbCRASP-1 and -2 preferentially bind factor H-like protein, while BbCRASP-3, -4 and -5 selectively bind factor H-related protein. BbCRASPs also vary in their Silmitasertib interaction with uncharacterized serum proteins. Though the binding affinities and the expression profiles of the BbCRASPs have been studied, the independent role of each BbCRASP in B. burgdorferi infectivity is not clear. Recently studies using a non-infectious mutant demonstrated that the loss of BbCRASP-1 sensitized the B. burgdorferi to complement-mediated lysis in human serum, an effect that can be rescued with gene complementation. While there is some disagreement as to the expression of BbCRASP-1 during mammalian infection, RT-PCR analysis indicate that it is only expressed transiently at the tick bite site and in ticks, but not expressed in mice. BbCRASP-1 therefore, may not play an essential role in mammalian infection, but could be important in spirochete survival in feeding ticks. Although the above set of studies suggest an important role for BbCRASPs in spirochete immune evasion, the precise role of individual BbCRASPs, or their orchestrated role in the B. burgdorferi infection cycle is not clear, largely because infectious BbCRASP-deficient B. burgdorferi have not yet been successfully generated. BbCRASP-2 is expressed by B. burgdorferi during murine infection, and infected hosts, including human patients, readily generate BbCRASP-2-specific antibodies. This protein is conserved among B. burgdorferi isolates, reported to be localized on the spirochete surface and has recently been suggested as a possible target for a second generation Lyme disease vaccine. The previous studies also suggest a possible functional role for BbCRASP-2 in immune evasion and pathogen survival. In order to test this hypothesis, we sought to determine CT99021 in vivo whether BbCRASP-2 is consistently produced in diverse murine tissues throughout the infection, and whether BbCRASP-2 immunization could provide host immunity and influence disease outcome. To explore the precise role of BbCRASP-2 in B. burgdorferi infectivity of a mammalian host, we assessed how targeted deletion of BbCRASP-2 in an infectious isolate influences B. burgdorferi infection in the murine model of Lyme borreliosis. Functional characterization of microbial ligands that are differentially expressed in the complex enzootic cycle of B. burgdorferi is critical to understanding the adaptive strategies of a pathogen that has evolved to persist in diverse tissue environments resulting in multi-system disorders.