DksA Controls the Response of the Lyme Disease Spirochete Borrelia burgdorferi to Starvation

William K. Boyle, Ashley M. Groshong, Dan Drecktrah, Julie A. Boylan, Frank C. Gherardini, Jon S. Blevins, D. Scott Samuels, Travis J. Bourret

Research output: Contribution to journalArticle

Abstract

The pathogenic spirochete Borrelia burgdorferi senses and responds to changes in the environment, including changes in nutrient availability, throughout its enzootic cycle in Ixodes ticks and vertebrate hosts. This study examined the role of DnaK suppressor protein (DksA) in the transcriptional response of B. burgdorferi to starvation. Wild-type and dksA mutant B. burgdorferi strains were subjected to starvation by shifting cultures grown in rich complete medium, Barbour-Stoenner-Kelly II (BSK II) medium, to a defined mammalian tissue culture medium, RPMI 1640, for 6 h under microaerobic conditions (5% CO2, 3% O2). Microarray analyses of wild-type B. burgdorferi revealed that genes encoding flagellar components, ribosomal proteins, and DNA replication machinery were downregulated in response to starvation. DksA mediated transcriptomic responses to starvation in B. burgdorferi, as the dksA-deficient strain differentially expressed only 47 genes in response to starvation compared to the 500 genes differentially expressed in wild-type strains. Consistent with a role for DksA in the starvation response of B. burgdorferi, fewer CFU of dksA mutants were observed after prolonged starvation in RPMI 1640 medium than CFU of wild-type B. burgdorferi spirochetes. Transcriptomic analyses revealed a partial overlap between the DksA regulon and the regulon of RelBbu, the guanosine tetraphosphate and guanosine pentaphosphate [(p)ppGpp] synthetase that controls the stringent response; the DksA regulon also included many plasmid-borne genes. Additionally, the dksA mutant exhibited constitutively elevated (p)ppGpp levels compared to those of the wild-type strain, implying a regulatory relationship between DksA and (p)ppGpp. Together, these data indicate that DksA, along with (p)ppGpp, directs the stringent response to effect B. burgdorferi adaptation to its environment.IMPORTANCE The Lyme disease bacterium Borrelia burgdorferi survives diverse environmental challenges as it cycles between its tick vectors and various vertebrate hosts. B. burgdorferi must withstand prolonged periods of starvation while it resides in unfed Ixodes ticks. In this study, the regulatory protein DksA is shown to play a pivotal role controlling the transcriptional responses of B. burgdorferi to starvation. The results suggest that DksA gene regulatory activity impacts B. burgdorferi metabolism, virulence gene expression, and the ability of this bacterium to complete its natural life cycle.

Original languageEnglish (US)
JournalJournal of Bacteriology
Volume201
Issue number4
DOIs
StatePublished - Feb 15 2019

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Borrelia burgdorferi
Starvation
Regulon
Ticks
Ixodes
Spirochaetales
Genes
Guanosine Pentaphosphate
Vertebrates
Guanosine Tetraphosphate
Bacteria
Lyme Disease
Ribosomal Proteins
Regulator Genes
Microarray Analysis
Ribosomal DNA
Life Cycle Stages
DNA Replication
Virulence
Culture Media

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

Cite this

Boyle, W. K., Groshong, A. M., Drecktrah, D., Boylan, J. A., Gherardini, F. C., Blevins, J. S., ... Bourret, T. J. (2019). DksA Controls the Response of the Lyme Disease Spirochete Borrelia burgdorferi to Starvation. Journal of Bacteriology, 201(4). https://doi.org/10.1128/JB.00582-18

DksA Controls the Response of the Lyme Disease Spirochete Borrelia burgdorferi to Starvation. / Boyle, William K.; Groshong, Ashley M.; Drecktrah, Dan; Boylan, Julie A.; Gherardini, Frank C.; Blevins, Jon S.; Samuels, D. Scott; Bourret, Travis J.

In: Journal of Bacteriology, Vol. 201, No. 4, 15.02.2019.

Research output: Contribution to journalArticle

Boyle, WK, Groshong, AM, Drecktrah, D, Boylan, JA, Gherardini, FC, Blevins, JS, Samuels, DS & Bourret, TJ 2019, 'DksA Controls the Response of the Lyme Disease Spirochete Borrelia burgdorferi to Starvation', Journal of Bacteriology, vol. 201, no. 4. https://doi.org/10.1128/JB.00582-18
Boyle WK, Groshong AM, Drecktrah D, Boylan JA, Gherardini FC, Blevins JS et al. DksA Controls the Response of the Lyme Disease Spirochete Borrelia burgdorferi to Starvation. Journal of Bacteriology. 2019 Feb 15;201(4). https://doi.org/10.1128/JB.00582-18
Boyle, William K. ; Groshong, Ashley M. ; Drecktrah, Dan ; Boylan, Julie A. ; Gherardini, Frank C. ; Blevins, Jon S. ; Samuels, D. Scott ; Bourret, Travis J. / DksA Controls the Response of the Lyme Disease Spirochete Borrelia burgdorferi to Starvation. In: Journal of Bacteriology. 2019 ; Vol. 201, No. 4.
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