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.

齿垢密螺旋体是一种螺旋体，是牙周病的病因。该细菌是两种牙周病原体之一，已被证明具有完整的三步酶促途径 (GTSP)，可将谷胱甘肽分解代谢为 H ₂ S。该途径可能有助于牙周炎中所见的组织病理学，因为患病的牙周袋具有较低的谷胱甘肽水平与 H ₂ S 浓度伴随增加的健康部位相比。为了能够证明 GTSP 的谷胱甘肽分解代谢对于T的致病潜力至关重要。denticola 中，使用等位基因替换诱变在编码 GTSP 中第一个酶的基因中产生缺失突变体 (Δ ggt )。该突变体不能从谷胱甘肽产生H ₂ S，因为它缺乏γ-谷氨酰转移酶(GGT) 活性。野生型T的溶血和血氧化活性。Δ ggt突变体将Denticola加谷胱甘肽降低至背景水平，并且当与谷胱甘肽一起孵育时，突变体失去了有氧生长的能力。与野生型T相比，含有谷胱甘肽的Δ ggt细菌在体外引起人牙龈成纤维细胞 (hGF) 的细胞死亡较少。denticola和 hGF 死亡水平与产生的 H ₂ S 量相关。重要的是，在评估软组织破坏（牙周病的主要症状）的小鼠背部病变模型中，突变螺旋体加谷胱甘肽产生的病变明显小于野生型细菌加谷胱甘肽。我们的结果首先证明了T。牙菌硫醇化合物通过其γ-谷氨酰转移酶的分解代谢在牙周炎中所见的宿主组织损伤类型中发挥重要作用。