# Regulation of glycerol utilization in Borrelia burgdorferi

> **NIH NIH R01** · UNIVERSITY OF MONTANA · 2020 · $438,748

## Abstract

PROJECT SUMMARY/ABSTRACT
Lyme disease is caused by infection with the spirochete Borrelia burgdorferi. B. burgdorferi is maintained in
nature in an enzootic cycle comprising a tick vector and vertebrate host. The spirochete shifts its source of
carbon and energy from glucose in the vertebrate to glycerol in the tick: utilization of glycerol is a crucial
adaptation for the spirochete to persist in the tick and successfully transmit to a vertebrate. We hypothesize
that the interface of glycerol metabolism and glycolysis, linked by interconversion of glycerol-3-phosphate and
dihydroxyacetone phosphate, is the metabolic linchpin for navigating the enzootic cycle. The central hypothesis
of this application is that B. burgdorferi post-transcriptionally regulates expression of the glycerol metabolism
(glp) operon to utilize glycerol in order to survive in its tick vector. We endeavor to dissect the molecular
mechanisms regulating expression of the glp operon, including the specific roles of a novel antisense RNA and
the cyclic-dimeric GMP (c-di-GMP)-binding protein PlzA. The following specific aims are proposed toward
achieving this objective: 1) define the role of the genes involved in glycerol metabolism during the enzootic
cycle; 2) determine the molecular mechanism of glp operon regulation; and 3) define the function of PlzA and
determine its role in regulating the glp operon. Genetic, biochemical, molecular, and transcriptomic
approaches, as well as the tick-mouse model of Lyme disease, will be utilized to experimentally test these
hypotheses. In this innovative application, the Multiple-PIs are in the unique position of having the experience,
expertise, and experimental models to enhance the mechanistic understanding of carbohydrate metabolism
and its regulation during the persistence of the Lyme disease agent in its tick vector. The long-term objective of
this proposal is to understand the regulatory mechanisms that allow B. burgdorferi to respond and adapt to
varied carbon sources in the tick-to-mammal transmission and in Lyme disease pathogenesis, which will lead
to improved diagnostic, prevention, and treatment strategies because glycerol and glucose utilization are
critical for persistence during tick and vertebrate infection, respectively; this is relevant to the mission of the
agency to “seek fundamental knowledge” for the sake of alleviating human disease.

## Key facts

- **NIH application ID:** 9948558
- **Project number:** 5R01AI130247-03
- **Recipient organization:** UNIVERSITY OF MONTANA
- **Principal Investigator:** Dan Drecktrah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $438,748
- **Award type:** 5
- **Project period:** 2018-06-08 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948558

## Citation

> US National Institutes of Health, RePORTER application 9948558, Regulation of glycerol utilization in Borrelia burgdorferi (5R01AI130247-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948558. Licensed CC0.

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