http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002102
Borrelia burgdorferi Requires Glycerol for Maximum Fitness During The
Tick Phase of the Enzootic Cycle
Christopher J. Pappas1, Radha Iyer1, Mary M. Petzke1, Melissa J.
Caimano2, Justin D. Radolf2,3,4, Ira Schwartz1*
1 Department of Microbiology and Immunology, New York Medical College,
Valhalla, New York, United States of America, 2 Department of Medicine,
University of Connecticut Health Center, Farmington, Connecticut, United
States of America, 3 Department of Genetics and Developmental Biology,
University of Connecticut Health Center, Farmington, Connecticut, United
States of America, 4 Department of Pediatrics, University of Connecticut
Health Center, Farmington, Connecticut, United States of America
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.
Author Summary
Borrelia burgdorferi is the vector-borne pathogen that causes Lyme
disease. It has a complex life cycle that involves growth in a tick
vector and a mammalian host — two diverse environments that present B.
burgdorferi with alternative carbohydrate sources for support of growth.
Previous studies suggested that glycerol may be an important nutrient in
the tick vector. Here we show that genes predicted to be involved in
glycerol metabolism have significantly elevated expression during all
tick stages. Repression of expression in the mammalian host is dependent
on the alternative sigma factor, RpoS. A mutant that cannot convert
glycerol into dihydroxyacetone phosphate to support glycolysis was able
to infect mice. In contrast, the mutant was present at significantly
lower levels in nymphal ticks, its replication was delayed during
nymphal feeding and longer feeding times were required for transmission
from nymph to mouse. 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.
Citation: Pappas CJ, Iyer R, Petzke MM, Caimano MJ, Radolf JD, et al.
(2011) Borrelia burgdorferi Requires Glycerol for Maximum Fitness During
The Tick Phase of the Enzootic Cycle. PLoS Pathog 7(7): e1002102.
doi:10.1371/journal.ppat.1002102
Editor: Jenifer Coburn, Medical College of Wisconsin, United States of
America
Received: March 2, 2011; Accepted: April 18, 2011; Published: July 7, 2011
Copyright: © 2011 Pappas et al. This is an open-access article
distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are credited.
Funding: This work was supported by NIH grants AI045801 (IS), AI29735
(JDR and MJC), AI085248 (MJC), and ARRA supplement AI045801-09S1 (IS)
(www.nih.gov) and a grant from the National Research Fund for Tick-Borne
Diseases (MJC) (www.nrftd.org). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
Competing interests: The authors have declared that no competing
interests exist.
* E-mail: Schwartz@nymc.edu
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