Functional Equivalence of OspA and OspB, but Not OspC, in Tick Colonization by Borrelia burgdorferi

Abstract

Borrelia burgdorferi, a Lyme disease agent, makes different major outer surface lipoproteins at different stages of its mouse-tick infectious cycle. Outer surface protein A (OspA) coats the spirochetes from the time they enter ticks until they are transmitted to a mammal. OspA is required for normal tick colonization and has been shown to bind a tick midgut protein, indicating that OspA may serve as a tick midgut adhesin. Tick colonization by spirochetes lacking OspA is increased when the infecting blood meal is derived from mice that do not produce antibody, indicating that OspA may protect the spirochetes from host antibody, which will not recognize tick-specific proteins such as OspA. To further study the importance of OspA during tick colonization, we constructed a form of B. burgdorferi in which the ospA open reading frame, on lp54, was replaced with the ospC gene or the ospB gene, encoding a mammal-specific or tick-specific lipoprotein, respectively. These fusions yielded a strain that produces OspC within a tick (from the fusion gene) and during early mammalian infection (from the normal ospC locus) and a strain that produces OspB in place of OspA within ticks. Here we show that the related, tick-specific protein OspB can fully substitute for OspA, whereas the unrelated, mammal-specific protein OspC cannot. These data were derived from three different methods of infecting ticks, and they confirm and extend previous studies indicating that OspA both protects spirochetes within ticks from mammalian antibody and serves an additional role during tick colonization.

Comparative transcriptomic analysis of Rickettsia conorii during in vitro infection of human and tick host cells

“…Comparative transcriptomic analysis of A. phagocytophilum grown in human (HL-60) and tick (ISE6) cells results in differential expression of 41.5% of the genes, of which 117 exhibit greater than two-fold change [12]. In Borrelia, OspA is highly expressed during its colonization in ticks, and OspC is upregulated during tick feeding and transmission, leading to the hypothesis that warm host blood and changes in the temperature during feeding act as a trigger for the modulation of gene expression [13,14]. Further, Borrelia OspB mutants exhibit impaired ability to adhere to gut tissues and survive in tick vectors despite their ability to infect and persist in mice [15].…”

High conservation combined with high plasticity: genomics and evolution of Borrelia bavariensis

“…OspA and OspB could possibly be associated with evasion of the tick immune system as both genes are known to be expressed during infection of the tick [77] . Genetic variation at the ospA locus has already been observed in B. garinii [78] .…”

Spirochetal Lipoproteins and Immune Evasion

“…Elimination of the ability to undergo antigenic variation, as was done in Borrelia hermsii , may greatly reduce host infectivity/persistence (119). Understanding the exact mechanisms behind a spirochete’s ability to elicit immune evasion via antigenic variation could set the basis for targeted interventions to inhibit infections (122). …”