Abstract
Borrelia burgdorferi, the spirochetal agent of Lyme disease, is a vector-borne pathogen that cycles between a mammalian host and tick vector. This complex life cycle requires that the spirochete modulate its gene expression program to facilitate growth and maintenance in these diverse milieus. B. burgdorferi contains an operon that is predicted to encode proteins that would mediate the uptake and conversion of glycerol to dihydroxyacetone phosphate. Previous studies indicated that expression of the operon is elevated at 23°C and is repressed in the presence of the alternative sigma factor RpoS, suggesting that glycerol utilization may play an important role during the tick phase. This possibility was further explored in the current study by expression analysis and mutagenesis of glpD, a gene predicted to encode glycerol 3-phosphate dehydrogenase. Transcript levels for glpD were significantly lower in mouse joints relative to their levels in ticks. Expression of GlpD protein was repressed in an RpoS-dependent manner during growth of spirochetes within dialysis membrane chambers implanted in rat peritoneal cavities. In medium supplemented with glycerol as the principal carbohydrate, wild-type B. burgdorferi grew to a significantly higher cell density than glpD mutant spirochetes during growth in vitro at 25°C. glpD mutant spirochetes were fully infectious in mice by either needle or tick inoculation. In contrast, glpD mutants grew to significantly lower densities than wild-type B. burgdorferi in nymphal ticks and displayed a replication defect in feeding nymphs. The findings suggest that B. burgdorferi undergoes a switch in carbohydrate utilization during the mammal to tick transition. Further, the results demonstrate that the ability to utilize glycerol as a carbohydrate source for glycolysis during the tick phase of the infectious cycle is critical for maximal B. burgdorferi fitness.
Highlights
Borrelia burgdorferi is the spirochetal agent of Lyme disease, the most frequently reported vector-borne disease in the United States [1]
B. burgdorferi glycerol 3-phosphate dehydrogenase (G3PDH) autoaligned with E. coli aerobic GlpD (PDB 2QCU), but not with E. coli GlpA [41] (Figure 2)
We propose that annotation of bb0243 should be changed to indicate that it putatively encodes an aerobic GlpD and B. burgdorferi G3PDH is referred to as GlpD in the remainder of this report
Summary
Borrelia burgdorferi is the spirochetal agent of Lyme disease, the most frequently reported vector-borne disease in the United States [1]. In the Northeastern United States, B. burgdorferi is transmitted between mammalian hosts by the bite of the black legged deer tick, Ixodes scapularis, with the white-footed mouse (Peromyscus leucopus) serving as the primary reservoir host [2,3]. B. burgdorferi are acquired by uninfected larvae feeding on an infected small mammal [4]. This is essential for the continued maintenance of B. burgdorferi in nature, since there is no transovarial transmission in Ixodes spp. The infected nymph will take a blood meal on a mammal, at which point B. burgdorferi multiply and begin their migration from the tick midgut to the salivary glands from which they are transmitted to a mammalian host [7,8,9], thereby completing the enzootic cycle
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