Thus, it appears that arp null spirochetes are equally (if not more) arthritogenic than wild-type B. burgdorferi in C3H-scid mice. The lack of effect on tissue burdens and arthritis in BALB/c-scid mice infected with B. burgdorferi devoid of the entire lp28-1 plasmid, but reduced burdens in infections with arp null spirochetes observed in the current study are likely due to the experimental GDC-0973 chemical structure variations in B. burgdorferi strains (B31-5A11 vs. B31-A3), mouse strains (BALB/c-scid vs. selleckchem C3H-scid), or a number of other

possible genetic variables. Lack of lp28-1 has been associated with failure to persist in immunocompetent mice. This has been attributed to vlsE, since clones lacking a region of the plasmid that encodes arp are capable of persistent infection [25, 29]. The current study examined persistence in immunocompetent C3H mice up to 42 days after inoculation, and demonstrated that arp null spirochetes were indeed capable of persistence. In the present study, we also infected mice for antibody evaluation at 60

days of culture-confirmed infection, and thus verified persistence for up to 60 days. As in C3H-scid mice, arp null spirochete burdens were lower in C3H mouse tissues compared to wild-type spirochetes. Notably, arthritis severity was markedly reduced in C3H mice infected with arp null spirochetes. Since arp null spirochetes are fully arthritogenic in SCID mice, these results suggest that the lower pathogenicity of arp null spirochetes in immunocompetent

mice is a consequence of susceptibility of the arp null mutant to immune response. Other antigens that are expressed selleck compound during infection have also been shown to be susceptible to arthritis-resolving antibody responses, PTK6 including DbpA [8], BmpA, and BmpB [30]. In the absence of Arp, these or other antigens may be targets of immune-mediated phenotypic effects noted in the present study. Although arp null spirochetes are capable of surviving in the murine host, their ability to do so appears to be compromised, since arp null spirochete burdens were 2 logs fewer in tissues of SCID mice compared to wild type spirochetes, and were even lower in immunocompetent mice. Thus, arp null spirochetes appear to be either less fit to grow or are more vulnerable to innate and acquired immune factors compared to wild type spirochetes. This lack of fitness is likely responsible for the additional phenotypic effect of arp deletion that was observed in acquisition and transmission by vector ticks. Larval ticks were fed upon mice infected with wild-type or arp null spirochetes, and allowed to molt into nymphs. Ticks became infected with both types of spirochetes, but following molting, nymphal ticks that were colonized with arp null spirochetes had significantly lower spirochete loads per tick compared to ticks colonized with wild type spirochetes.