Antimicrobial peptide GH12 targetsStreptococcus mutansto arrest caries development in rats

Abstract

Background:Targeting Streptococcus mutans, the principle cariogenic bacterium, could prove to be an effective means of preventing dental caries. A de novo designed antimicrobial peptide, GH12, has shown bactericidal effects on S. mutans and inhibitory effects on virulence and regulatory systems of S. mutans. However, the effects of GH12 on caries remain to be elucidated.Objectives: The objectives of this study were to evaluate the direct effects of GH12 on caries and numbers of S. mutansin vivo.Design: The Keyes score was evaluated in a rodent model and in vivo S. mutans was quantified by qPCR. To further interpret the in vivo anticaries efficacy, an in vitro biofilm model using short-term treatments with GH12 mimicked treatments in vivo was adopted. Results: In vivo data showed that GH12 at 8 mg/L reduced the incidence and severity of caries. Furthermore, GH12-treated animals had less S. mutans infection. In vitro data revealed that GH12 reduced the number of S. mutans within the biofilm, as well as reducing lactic acid and water-insoluble EPS synthesis of S. mutans biofilms. Afterwards, all rats showed no significant difference in weight gain, and no sign of harm to the mucosa, indicating that GH12 possessed good biocompatibility in vivo.Conclusion: Due to the combined inhibitory effects of GH12 on the biomass and cariogenic properties of S. mutans biofilms, the population of S. mutans in vivo was reduced, residual S. mutans biofilms were less acidic and compact, and thereby the onset and development of caries were arrested. Such findings collectively certified the clinical prospects for GH12. ARTICLE HISTORY

Antimicrobial Peptide GH12 Prevents Dental Caries by Regulating Dental Plaque Microbiota

“…1 and 2), which demonstrated that GH12 could suppress the cariogenic properties of dental plaque, prevent localized acidification, and make it easier to remove. In a previous study, 8-mg/liter GH12 suppressed the cariogenic properties of preformed S. mutans biofilms (18). However, in this study, GH12 at 8 mg/liter showed no inhibitory effects on the dental plaquederived multispecies biofilms and only a high concentration of GH12 of 64 mg/liter significantly suppressed the cariogenic properties of the dental plaque-derived multispecies biofilms.…”

“…In addition, GH12 inhibited the cariogenic properties of a threespecies biofilm and shifted the microbial composition to a healthier condition by suppressing S. mutans and favoring commensal streptococci (17). Furthermore, shortterm treatments with 8-mg/liter GH12 reduced the incidence and severity of caries in the rat caries model, and its effects on reducing the caries scores rivaled those of NaF and chlorhexidine (18). However, the anticaries effects and the microecological effects of GH12 remained to be further investigated in vitro and in vivo to evaluate its potential as an ecological caries prevention strategy.…”

Next‐generation Antimicrobial Peptides (AMPs) incorporated nanofibre wound dressings

“…Peptides have low toxicity (Yin et al, 2017), high specificity (Lombardi et al, 2019), and are readily synthesized or modified (Tesauro et al, 2019). GH12 is one of the well‐established antimicrobial peptides (Y. Wang et al, 2019). Previously, we have engineered a derivative of GH12, GH12‐M2 (GLLWHLLHHLLH_GSGGG_K) and showed its antimicrobial activity (Xie et al, 2019).…”

“…GH12 is one of the well-established antimicrobial peptides (Y. Wang et al, 2019). Previously, we have engineered a derivative of GH12, GH12-M2 (GLLWHLLHHLLH_GSGGG_K) and showed its antimicrobial activity (Xie et al, 2019).…”

Peptide Mediated Antimicrobial Dental Adhesive System

“…GH12 has been shown to reduce the cariogenic virulence factors of S. mutans , an activity that makes GH12 a candidate for dental caries prevention [ 68 ]. In addition, GH12 was successfully employed in a rodent model in a pioneer study aimed to analyze the efficacy of an antimicrobial peptide on the onset and development of dental caries [ 69 ]. Promising sequence derivatives were selected for synthesis through computational structure generation verified via analysis of GH12 and modified peptide folding using circular dichroism in the presence of a kosmotropic agent.…”