Pyruvate protects pathogenic spirochetes from H2O2 killing

Bryan Troxel, Jun Jie Zhang, Travis J. Bourret, Melody Yue Zeng, Janice Blum, Frank Gherardini, Hosni M. Hassan, X. Frank Yang

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Pathogenic spirochetes cause clinically relevant diseases in humans and animals, such as Lyme disease and leptospirosis. The causative agent of Lyme disease, Borrelia burgdorferi, and the causative agent of leptospirosis, Leptospria interrogans, encounter reactive oxygen species (ROS) during their enzootic cycles. This report demonstrated that physiologically relevant concentrations of pyruvate, a potent H2O2 scavenger, and provided passive protection to B. burgdorferi and L. interrogans against H 2O2. When extracellular pyruvate was absent, both spirochetes were sensitive to a low dose of H2O2 (≈0.6 mM per h) generated by glucose oxidase (GOX). Despite encoding a functional catalase, L. interrogans was more sensitive than B. burgdorferi to H 2O2 generated by GOX, which may be due to the inherent resistance of B. burgdorferi because of the virtual absence of intracellular iron. In B. burgdorferi, the nucleotide excision repair (NER) and the DNA mismatch repair (MMR) pathways were important for survival during H 2O2 challenge since deletion of the uvrB or the mutS genes enhanced its sensitivity to H2O2 killing; however, the presence of pyruvate fully protected ΔuvrB and ΔmutS from H 2O2 killing further demonstrating the importance of pyruvate in protection. These findings demonstrated that pyruvate, in addition to its classical role in central carbon metabolism, serves as an important H2O2 scavenger for pathogenic spirochetes. Furthermore, pyruvate reduced ROS generated by human neutrophils in response to the Toll-like receptor 2 (TLR2) agonist zymosan. In addition, pyruvate reduced neutrophil-derived ROS in response to B. burgdorferi , which also activates host expression through TLR2 signaling. Thus, pathogenic spirochetes may exploit the metabolite pyruvate, present in blood and tissues, to survive H 2O2 generated by the host antibacterial response generated during infection.

Original languageEnglish
Article numbere84625
JournalPLoS One
Volume9
Issue number1
DOIs
StatePublished - Jan 2 2014
Externally publishedYes

Fingerprint

Spirochaetales
Borrelia burgdorferi
Pyruvic Acid
reactive oxygen species
glucose oxidase
Lyme disease
leptospirosis
Toll-Like Receptor 2
Reactive Oxygen Species
Glucose Oxidase
Leptospirosis
Lyme Disease
neutrophils
diseases and disorders (animals and humans)
zymosan
Neutrophils
Repair
DNA repair
agonists
DNA Mismatch Repair

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Troxel, B., Zhang, J. J., Bourret, T. J., Zeng, M. Y., Blum, J., Gherardini, F., ... Yang, X. F. (2014). Pyruvate protects pathogenic spirochetes from H2O2 killing. PLoS One, 9(1), [e84625]. https://doi.org/10.1371/journal.pone.0084625

Pyruvate protects pathogenic spirochetes from H2O2 killing. / Troxel, Bryan; Zhang, Jun Jie; Bourret, Travis J.; Zeng, Melody Yue; Blum, Janice; Gherardini, Frank; Hassan, Hosni M.; Yang, X. Frank.

In: PLoS One, Vol. 9, No. 1, e84625, 02.01.2014.

Research output: Contribution to journalArticle

Troxel, B, Zhang, JJ, Bourret, TJ, Zeng, MY, Blum, J, Gherardini, F, Hassan, HM & Yang, XF 2014, 'Pyruvate protects pathogenic spirochetes from H2O2 killing', PLoS One, vol. 9, no. 1, e84625. https://doi.org/10.1371/journal.pone.0084625
Troxel B, Zhang JJ, Bourret TJ, Zeng MY, Blum J, Gherardini F et al. Pyruvate protects pathogenic spirochetes from H2O2 killing. PLoS One. 2014 Jan 2;9(1). e84625. https://doi.org/10.1371/journal.pone.0084625
Troxel, Bryan ; Zhang, Jun Jie ; Bourret, Travis J. ; Zeng, Melody Yue ; Blum, Janice ; Gherardini, Frank ; Hassan, Hosni M. ; Yang, X. Frank. / Pyruvate protects pathogenic spirochetes from H2O2 killing. In: PLoS One. 2014 ; Vol. 9, No. 1.
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