Pyruvate Protects Pathogenic Spirochetes from H2O2 Killing

dc.contributor.authorTroxell, Bryan
dc.contributor.authorZhang, Jun-Jie
dc.contributor.authorBourret, Travis J.
dc.contributor.authorZeng, Melody Yue
dc.contributor.authorBlum, Janice
dc.contributor.authorGherardini, Frank
dc.contributor.authorHassan, Hosni M.
dc.contributor.authorYang, X. Frank
dc.contributor.departmentMicrobiology and Immunology, School of Medicine
dc.date.accessioned2025-04-24T11:08:27Z
dc.date.available2025-04-24T11:08:27Z
dc.date.issued2014-01-02
dc.description.abstractPathogenic 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 H2O2. When extracellular pyruvate was absent, both spirochetes were sensitive to a low dose of H2O2 (≈0.6 µM per h) generated by glucose oxidase (GOX). Despite encoding a functional catalase, L. interrogans was more sensitive than B. burgdorferi to H2O2 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 H2O2 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 H2O2 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 H2O2 generated by the host antibacterial response generated during infection.
dc.eprint.versionFinal published version
dc.identifier.citationTroxell B, Zhang JJ, Bourret TJ, et al. Pyruvate protects pathogenic spirochetes from H2O2 killing. PLoS One. 2014;9(1):e84625. Published 2014 Jan 2. doi:10.1371/journal.pone.0084625
dc.identifier.urihttps://hdl.handle.net/1805/47404
dc.language.isoen_US
dc.publisherPublic Library of Science
dc.relation.isversionof10.1371/journal.pone.0084625
dc.relation.journalPLoS One
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePMC
dc.subjectBorrelia burgdorferi
dc.subjectSpirochaetales
dc.subjectNeutrophils
dc.subjectBacterial proteins
dc.subjectAcetates
dc.titlePyruvate Protects Pathogenic Spirochetes from H2O2 Killing
dc.typeArticle
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Troxell2014Pyruvate-CCBY.pdf
Size:
1.21 MB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2.04 KB
Format:
Item-specific license agreed upon to submission
Description: