Tannerella forsythia‐produced methylglyoxal causes accumulation of advanced glycation endproducts to trigger cytokine secretion in human monocytes

Abstract

The periodontal pathogen Tannerella forsythia has the unique ability to produce methylglyoxal (MGO), an electrophilic compound which can covalently modify amino acid side chains and generate inflammatory adducts known as advanced glycation endproducts (AGEs). In periodontitis, concentrations of MGO in gingival-crevicular fluid are increased and are correlated with the T. forsythia load. However, the source of MGO and the extent to which MGO may contribute to periodontal inflammation has not been fully explored. In this study we identified a functional homolog of the enzyme methylglyoxal synthase (MgsA) involved in the production of MGO in T. forsythia. While wild-type T.forsythia produced a significant amount of MGO in the medium, a mutant lacking this homolog produced little to no MGO. Furthermore, compared with the spent medium of the T. forsythia parental strain, the spent medium of the T. forsythia mgsA-deletion strain induced significantly lower nuclear factor-kappa B activity as well as proinflammogenic and pro-osteoclastogenic cytokines from THP-1 monocytes. The ability of T. forsythia to induce protein glycation endproducts via MGO was confirmed by an electrophoresis-based collagen chain mobility shift assay. Together these data demonstrated that T. forsythia produces MGO, which may contribute to inflammation via the generation of AGEs and thus act as a potential virulence factor of the bacterium.

Methylglyoxal-Dependent Glycative Stress Is Prevented by the Natural Antioxidant Oleuropein in Human Dental Pulp Stem Cells through Nrf2/Glo1 Pathway

“…Hence, MG-dependent glycative stress that, as observed here, impairs DPSC viability may have a crucial negative impact on the above-mentioned processes, with important pathological consequences. Additionally, mounting in vitro evidence, using cell models from gingival connective tissue, suggests that MG and MG-derived AGEs participate to the pathogenesis of some oral diseases, such as gingivitis and periodontitis [ 18 , 19 ], and some in vivo studies report the accumulation of MG in some biological fluids from gingival crevicular fluid of chronic periodontitis patients [ 20 ], where they can be conveyed by bacterial infections [ 20 , 21 ]. Moreover, MG is an endogenous metabolite but also a compound that can be introduced from some foodstuffs (e.g., milk, coffee, bread, fruit juices), food cooking, cigarette smoke or aerosols from nicotine delivery systems (NDS) [ 22 , 23 , 24 ].…”

“…Mounting in vitro evidence, using mainly cell models from gingival connective tissue, suggests that MG and MG-derived AGEs are also involved in the pathogenesis of some oral diseases, such as gingivitis and periodontitis [ 18 , 19 ]. Moreover, some in vivo observations have pointed out the accumulation of MG in some biological fluids from the gingival crevicular fluid of chronic periodontitis patients [ 20 ] that can also be conveyed by bacterial infections [ 21 ], dietary compounds [ 22 ], and cigarette smoke or aerosols from nicotine delivery systems (NDS) (Electronic Cigarette and Heat-not-burn tobacco product IQOS) [ 23 , 24 ]. Notably, numerous clinical and experimental studies have highlighted the presence of a strong association between periodontitis, which represents the most common pathology of the oral cave in the adult population, and some systemic diseases, in particular, diabetes and obesity [ 25 , 26 ], which, as mentioned before, are characterized by increased levels of MG and MG-derived “glycative stress” onset.…”

Oral, Tongue-Coating Microbiota, and Metabolic Disorders: A Novel Area of Interactive Research

“…Common harmful oral bacteria can damage immunity and cause chronic inflammation ( 51 , 52 ). Changes in the abundance of Enterococcus sp .…”

Communal interaction of glycation and gut microbes in diabetes mellitus, Alzheimer's disease, and Parkinson's disease pathogenesis

“…Glyoxal (GO) and MG formation are also reported in some gut microbes. 137,138 We have evaluated a high amount of GO and MG from yogurt (carbohydrate-rich) and 24 h curd set, interestingly when compared to 12 h curd set, in 24 h curd set tremendous increase in lactic acid bacteria was also noticed, advising controlled consumption and exemption in case of diabetes. 139 Sugar alters gut permeability by glycation and allows the microbes/metabolites to orchestrate the genesis of diseases via other consequences.…”