Interaction of the Lyme disease spirochete with its tick vector

Abstract

Borrelia burgdorferi, the causative agent of Lyme disease (along with closely related genospecies), is in the deeply branching spirochete phylum. The bacterium is maintained in nature in an enzootic cycle that involves transmission from a tick vector to a vertebrate host and acquisition from a vertebrate host to a tick vector. During its arthropod sojourn, B. burgdorferi faces a variety of stresses, including nutrient deprivation. Here, we review some of the spirochetal factors that promote persistence, maintenance and dissemination of B. burgdorferi in the tick, and then focus on the utilization of available carbohydrates as well as the exquisite regulatory systems invoked to adapt to the austere environment between blood meals and to signal species transitions as the bacteria traverse their enzootic cycle. The spirochetes shift their source of carbon and energy from glucose in the vertebrate to glycerol in the tick. Regulation of survival under limiting nutrients requires the classic stringent response in which RelBbu controls the levels of the alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively termed (p)ppGpp), while regulation at the tick-vertebrate interface as well as regulation of protective responses to the blood meal require the two-component system Hk1/Rrp1 to activate production of the second messenger cyclic-dimeric-GMP (c-di-GMP).

Fig. 1

The enzootic cycle of B. burgdorferi. Acquisition: larval ticks must acquire B. burgdorferi by feeding on an infected vertebrate as the bacterium is not transovarially transmitted. Persistence: intracellular second messengers (p)ppGpp and c-di-GMP regulate persistence in the tick by various mechanisms, including modulation of carbohydrate preference, while the molecular gatekeeper RpoS is absent in unfed ticks. Transmission: following the molt into nymphs, infected ticks can transmit B. burgdorferi to uninfected hosts, completing the cycle. Adapted from Brisson et al. (2012). GlcNAc, N-acetyl glucosamine.

Fig. 2

Schematic diagram of carbohydrate transport and metabolism based on functional studies and/or bioinformatics. Adapted from Corona and Schwartz (2015).