Glutathione catabolism by Treponema denticola impacts its pathogenic potential. (April 2020)

• Record Type: Journal Article
• Authors: Chu, Lianrui; Wu, Yimin; Xu, Xiaoping; Phillips, Linda; Kolodrubetz, David
• Is Part Of: Anaerobe. Volume 62(2020)
• Publication Date: 2020-04
• Subjects: Treponema denticola -- ggt mutant -- Periodontal disease -- Gingival fibroblast death -- Glutathione catabolism; Anaerobic infections -- Periodicals; Anaerobic bacteria -- Periodicals; Bacterial diseases -- Periodicals; Computer network resources; Anaerobic protozoa -- Periodicals; 579.3
• DOI: 10.1016/j.anaerobe.2020.102170
• Languages: English
• ISSNs: 1075-9964

Abstract

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 H2 S. 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 H2 S 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 (Δ ggt ) in the gene encoding the first enzyme in the GTSP. The mutant cannot produce H2 S 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 Δ ggt mutant and the mutant has lost the ability to grow aerobically when incubated with glutathione. The Δ ggt 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 H2 S 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. Highlights: T. denticola lacking γ-glutamyl transferase ( Δggt ) cannot make H2 S from glutathione. The T. denticola Δggt mutant has decreased hemolytic and hemoxidative activity. T. denticola does not grow aerobically without γ-glutamyl transferase activity. Without GGT, T. denticola does not fully induce cell death in gingival fibroblasts. The T. denticola Δggt mutant makes smaller lesions in a mouse back abscess model.