Exposure of P. gingivalis to noradrenaline reduces bacterial growth and elevates ArgX protease activity

Abstract

Objective: Periodontitis, an infectious disease caused by periodontopathic bacteria, including Porphyromonas gingivalis and spirochetes, is reported to be accelerated by stress, under which noradrenaline levels are increased in the bloodstream. The purpose of this study was to evaluate the effects of noradrenaline on P. gingivalis. Design: P. gingivalis was incubated in the presence of 25 µM, 50 µΜ, or 100 µM adrenaline or noradrenaline at 37°C for 12, 24 or 36 h and growth was evaluated by OD 660 .Auto-inducer-2 (AI-2) was measured by luminescence of Vibrio harveyi BB 170.Expression of P. gingivalis genes was evaluated using a microarray and RT-PCR. Rgp activity of arg-gingipainA and B (Rgp) was measured with a synthetic substrate.Results: Growth of P. gingivalis FDC381 was inhibited by noradrenaline at 24 and 36 h.Growth inhibition by noradrenaline increased dose-dependently. Inhibition of growth partially recovered with addition of propranolol. AI-2 production from P. gingivalis showed a marked decrease with addition of noradrenaline compared with peak production levels in the control group. Microarray analysis revealed an increase in expression in 18 genes and a decrease in expression in 2 genes. Among these genes, expression of the protease arg-gingipainB (RgpB) gene, a major virulence factor of P.gingivalis, was further analyzed. Expression of rgpB showed a significant increase with addition of noradrenaline, which was partially reduced by addition of propranolol.Cell-associated Rgp activity also increased with addition of noradrenaline.Conclusions: These results suggest that stressors influence the expression of the virulence factors of P. gingivalis via noradrenaline.3

Melatonin Receptor Agonists as the “Perioceutics” Agents for Periodontal Disease through Modulation of Porphyromonas gingivalis Virulence and Inflammatory Response

“…Rag is the homolog of TonB-linked outer membrane receptors and involved in the acquisition of iron in Porphyromonas gingivalis [55–57]. Rgp B plays a critical role in the periodontal disease because it is in charge of the production of gingipains [55,58,59]. Consistent with the above result, the above virulence-related genes were suppressed by melatonin and ramelteon, which may play a role in their antimicrobial and antiprotease activities.…”

Effects of stress hormones on the production of volatile sulfur compounds by periodontopathogenic bacteria

“…It was reported that the growth rate of Pg was reduced when exposed to catecholamines. 13,15 Additionally, cortisol was demonstrated to stimulate the growth of Pg cultures. 24 Our results showed no effects of NA, ADR or CORT on the growth rate of this pathogen.…”

“…11 These microorganisms could use the hormones produced by the host as 'environmental trails' to initiate their growth and pathogenic processes. 12,13,14,15,16,17 In one study, the growth rate of bacteria commonly found in the oral cavity, such as Actinomyces naeslundii, Eikenella corrodens, and Campylobacter gracilis, was stimulated by exposure to noradrenaline. 13 In addition, recent studies show conflicting results of noradrenaline and adrenaline on the growth of P. gingivalis, with studies showing either no effects of these hormones on growth 12,17 or demonstrating a reduction in viability.…”

“…13 In addition, recent studies show conflicting results of noradrenaline and adrenaline on the growth of P. gingivalis, with studies showing either no effects of these hormones on growth 12,17 or demonstrating a reduction in viability. 13,15 Recently, it was demonstrated that noradrenaline can stimulate the production and activity of arg-gingipain B, an important protease of P. gingivalis. 15 Thus, the effects of stress could be mediated by two potentially synergistic pathways involving the downregulation of the host's defenses and the up-regulation of bacterial pathogenicity.…”

“…13,15 Recently, it was demonstrated that noradrenaline can stimulate the production and activity of arg-gingipain B, an important protease of P. gingivalis. 15 Thus, the effects of stress could be mediated by two potentially synergistic pathways involving the downregulation of the host's defenses and the up-regulation of bacterial pathogenicity.…”