Glutathione catabolism by Treponema denticola impacts its pathogenic potential

Lianrui Chu, Yimin Wu, Xiaoping Xu, Linda Phillips, David Kolodrubetz

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Treponema denticola is a spirochete that is etiologic for periodontal diseases. This bacterium is one of two periodontal pathogens that have been shown to have a complete three step enzymatic pathway (GTSP) that catabolizes glutathione to H2S. This pathway may contribute to the tissue pathology seen in periodontitis since diseased periodontal pockets have lower glutathione levels than healthy sites with a concomitant increase in H2S concentration. In order to be able to demonstrate that glutathione catabolism by the GTSP is critical for the pathogenic potential of T. denticola, allelic replacement mutagenesis was used to make a deletion mutant (Δggt) in the gene encoding the first enzyme in the GTSP. The mutant cannot produce H2S from glutathione since it lacks gamma-glutamyltransferase (GGT) activity. The hemolytic and hemoxidation activities of wild type T. denticola plus glutathione are reduced to background levels with the Δggt mutant and the mutant has lost the ability to grow aerobically when incubated with glutathione. The Δggt bacteria with glutathione cause less cell death in human gingival fibroblasts (hGFs) in vitro than do wild type T. denticola and the levels of hGF death correlate with the amounts of H2S produced. Importantly, the mutant spirochetes plus glutathione make significantly smaller lesions than wild type bacteria plus glutathione in a mouse back lesion model that assesses soft tissue destruction, a major symptom of periodontal diseases. Our results are the first to prove that T. denticola thiol-compound catabolism by its gamma-glutamyltransferase can play a significant role in the in the types of host tissue damage seen in periodontitis.

Original languageEnglish (US)
Article number102170
JournalAnaerobe
Volume62
DOIs
StatePublished - Apr 2020

Keywords

  • ggt mutant
  • Gingival fibroblast death
  • Glutathione catabolism
  • Periodontal disease
  • Treponema denticola

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

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