Borrelia burgdorferi complement regulator-acquiring surface proteins: Expression during the Lyme disease spirochete's mammal-tick infection cycle

Borrelia burgdorferi , the etiological agent of Lyme disease, is innately resistant to killing by host complement. One proposed mechanism for this resistance is the ability of B. burgdorferi to bind host factor H and factor H-like protein 1 (FHL-1), the fluid-phase regulators of the alternative complement pathway. CRASP-2 (CspZ) protein is evolutionary highly conserved among different strains and isolates of B. burgdorferi sensu lato but unrelated to other CRASPs. It is capable of binding both factor H and FHL-1. Examination of CspZ protein synthesis in vivo by immunofluorescence (IFA) and in cultured spirochetes demonstrated differences in expression patterns compared to other, previously studied B. burgdorferi complement regulator-acquiring surface proteins (BbCRASPs). The extensive differences between the 5’-noncoding regions of all the genes encoding BbCRASPs suggest that each may be controlled through different molecular mechanism, and possibly be expressed at different stages of the bacterial infectious cycle. That prediction was tested by an extensive comparison of transcript levels of all four BbCRASPs encoded by a clonal population of B. burgdorferi , throughout the mammal-tick infection cycle. Although the expression of some of BbCRASP-encoding genes is markedly elevated during tick to mammal transmission stage, the molecular mechanism responsible for that phenomenon is clearly novel and different than the earlier described cascade of RpoN/RpoS RNA polymerase sigma factors.