Borrelia burgdorferi Alters Its Gene Expression and Antigenic Profile in Response to CO ₂ Levels

Abstract

The etiologic agent of Lyme disease, Borrelia burgdorferi, must adapt to the distinct environments of its arthropod vector and mammalian host during its complex life cycle. B. burgdorferi alters gene expression and protein synthesis in response to temperature, pH, and other uncharacterized environmental factors. The hypothesis tested in this study is that dissolved gases, including CO 2 , serve as a signal for B. burgdorferi to alter protein production and gene expression. In this study we focused on characterization of in vitro anaerobic (5% CO 2 , 3% H 2 , 0.087 ppm O 2 ) and microaerophilic (1% CO 2 , 3.48 ppm O 2 ) growth conditions and how they modulate protein synthesis and gene expression in B. burgdorferi. Higher levels of several immunoreactive proteins, including BosR, NapA, DbpA, OspC, BBK32, and RpoS, were synthesized under anaerobic conditions. Previous studies demonstrated that lower levels of NapA were produced when microaerophilic cultures were purged with nitrogen gas to displace oxygen and CO 2 . In this study we identified CO 2 as a factor contributing to the observed change in NapA synthesis. Specifically, a reduction in the level of dissolved CO 2 , independent of O 2 levels, resulted in reduced NapA synthesis. BosR, DbpA, OspC, and RpoS synthesis was also decreased with the displacement of CO 2 . Quantitative reverse transcription-PCR indicated that the levels of the dbpA, ospC, and BBK32 transcripts are increased in the presence of CO 2 , indicating that these putative borrelial virulence determinants are regulated at the transcriptional level. Thus, dissolved CO 2 may be an additional cue for borrelial host adaptation and gene regulation.

Oligopeptide Permease A5 Modulates Vertebrate Host-Specific Adaptation of Borrelia burgdorferi

“…A large number of studies have demonstrated the importance of vertebrate host-specific factors associated with the incoming blood meal in the midgut of ticks in modulating adaptive gene expression in B. burgdorferi (20,22,25,39,71,72,77). The resultant phenotypic changes in the spirochetes, in turn, contribute to their transmission from the tick vector and subsequently facilitate colonization of the vertebrate hosts (28, 32, 35, 36, 63).…”

“…A broad array of studies using global gene expression arrays has provided clues to contributions of genes individually or at a global level that facilitate host-specific adaptation of B. burgdorferi (4,6,12,17,55,65,83). Environmental conditions such as temperature (71), cell density (40), pH (19,20), levels of dissolved gases (39,72), and other components that are significantly different between the tick vector and vertebrate hosts (7,8,23) have been used to decipher both the transcriptional levels of genes and the regulatory networks involved in modulating this response (5, 14-16, 32, 47, 49, 91).…”

Lactobacillus plantarum response to inorganic carbon concentrations: PyrR2-dependent and -independent transcription regulation of genes involved in arginine and nucleotide metabolism

“…Several virulence genes are also regulated in response to C i availability. CO 2 /bicarbonate is likely to be a physiologically significant signal encountered by pathogens in the host environment (Drysdale et al, 2005;Herbert et al, 2001;Koehler, 2002;Hyde et al, 2007). C i -responding regulation is not restricted to carbon assimilation or virulence genes.…”

Borrelia burgdorferi bba74Is Expressed Exclusively during Tick Feeding and Is Regulated by Both Arthropod- and Mammalian Host-Specific Signals

“…To successfully complete this life cycle, B. burgdorferi must adapt to and propagate within two markedly different physiologic milieus (67,75,96). A number of investigators have reported that manipulation of parameters, such as temperature, pH, DNA supercoiling, cell density, and partial O 2 pressure, during in vitro cultivation can trigger changes in gene and protein expression resembling those that occur when spirochetes adapt to their mammalian host (4,20,21,44,45,65,74,77,78,89,102). It also is now evident, however, that spirochetes must be exposed to as yet unidentified mammalian host-specific signals to induce the full range of transcriptional and translational changes that occur during infection (1,13,17,19,39,97).…”