Borrelia burgdorferi: Carbon Metabolism and the Tick-Mammal Enzootic Cycle

Abstract

Borrelia burgdorferi, the spirochetal agent of Lyme disease, is a zoonotic pathogen that is maintained in a natural cycle that typically involves mammalian reservoir hosts and a tick vector of the Ixodes species. During each stage of the enzootic cycle, B. burgdorferi is exposed to environments that differ in temperature, pH, small molecules, and most important, nutrient sources. B. burgdorferi has a highly restricted metabolic capacity because it does not contain a tricarboxylic acid cycle, oxidative phosphorylation, or any pathways for de novo biosynthesis of carbohydrates, amino acids, or lipids. Thus, B. burgdorferi relies solely on glycolysis for ATP production and is completely dependent on the transport of nutrients and cofactors from extracellular sources. Herein, pathways for carbohydrate uptake and utilization in B. burgdorferi are described. Regulation of these pathways during the different phases of the enzootic cycle is discussed. In addition, a model for differential control of nutrient flux through the glycolytic pathway as the spirochete transits through the enzootic cycle is presented.

Figure 1

Borrelia burgdorferi enzootic cycle. (1) Uninfected larva emerges from eggs. (2) Larval acquisition of B. burgdorferi during a blood meal on an infected reservoir host. (3) Infected fed larva molts to an unfed nymph. (4) Transmission of B. burgdorferi from a feeding nymph to an uninfected reservoir host during the nymphal blood meal. (5) Infected fed nymph molts to an adult. (6) Female and male adults mate on a large mammal (typically deer). The female adult feeds on the large mammal and lays eggs.

Figure 2

Borrelia burgdorferi carbohydrate transporters. Schematic diagram indicates predicted or experimentally verified transport systems. BB numbers indicate gene locus in B. burgdorferi strain B31 (17). Based on von Lackum and Stevenson (81).

Figure 3

The glycolytic pathway and control of glycolytic flux during the enzootic cycle.

Figure 4

Schematic diagram depicting reported regulatory circuits controlling glycerol and chitobiose utilization. Solid lines indicate interactions confirmed by in vivo studies; dashed lines indicate interactions observed in vitro only. Diagram is summary of data from references , , , , , , , , , and .