Antimicrobial peptides and periodontal disease

Abstract

Aims: The goal of this review is to identify the antimicrobial proteins in the oral fluids, saliva and gingival crevicular fluid and identify functional families and candidates for antibacterial treatment. Results: Periodontal biofilms initiate a cascade of inflammatory and immune processes that lead to the destruction of gingival tissues and ultimately alveolar bone loss and tooth loss. Treatment of periodontal disease with conventional antibiotics does not appear to be effective in the absence of mechanical debridement. An alternative treatment may be found in antimicrobial peptides and proteins, which can be bactericidal and anti-inflammatory and block the inflammatory effects of bacterial toxins. The peptides have co-evolved with oral bacteria, which have not developed significant peptide resistance. Over 45 antibacterial proteins are found in human saliva and gingival crevicular fluid. The proteins and peptides belong to several different functional families and offer broad protection from invading microbes. Several antimicrobial peptides and proteins (AMPs) serve as templates for the development of therapeutic peptides and peptide mimetics, although to date none have demonstrated efficacy in human trials. Conclusions: Existing and newly identified AMPs may be developed for therapeutic use in periodontal disease or can serve as templates for peptide and peptide mimetics with improved therapeutic indices.

<b>Vitamin D</b><b>₃</b><b> analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial </b><b>cells </b>

“…4, 80% and almost 100% of the bacteria were killed by treatment with 5 and 20 μg/mL of LL-37 peptide for 30 min, respectively. LL-37 has been shown to exert antimicrobial activity against oral periodontopathic bacteria, P. gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and Fusobacterium nucleatum (6). It has been reported that LL-37 neutralizes LPS from P. gingivalis and inhibits LPS-induced inflammatory cytokine production (27).…”

Antimicrobial Peptides: Mechanisms of Action and Resistance

“…We hypothesized that the diverse functional classeswhich include cationic peptides, bacterial agglutination and adhesion, metal ion chelators, peroxidase activity, cell wall activity, and proteolytic inhibitors (Gorr 2009;Gorr and Abdolhosseini 2011)-enhance the antibacterial activity of oral fluids and limit the development of bacterial resistance to endogenous AMPs, although it should be noted that the in vivo function of individual AMPs is not entirely clear and a single AMP may exhibit multiple functions. Several AMPs are found in the oral cavity in concentrations below the experimentally determined minimal inhibitory concentration (MIC), casting some doubt on their antibacterial activity in the oral cavity (Gorr and Abdolhosseini 2011).…”

“…We hypothesized that the diverse functional classeswhich include cationic peptides, bacterial agglutination and adhesion, metal ion chelators, peroxidase activity, cell wall activity, and proteolytic inhibitors (Gorr 2009;Gorr and Abdolhosseini 2011)-enhance the antibacterial activity of oral fluids and limit the development of bacterial resistance to endogenous AMPs, although it should be noted that the in vivo function of individual AMPs is not entirely clear and a single AMP may exhibit multiple functions. Several AMPs are found in the oral cavity in concentrations below the experimentally determined minimal inhibitory concentration (MIC), casting some doubt on their antibacterial activity in the oral cavity (Gorr and Abdolhosseini 2011). As an example, ß-defensins are found in saliva at concentrations that are 1 to 2 orders of magnitude below the MIC for several oral bacteria, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Streptococcus mutans (Gorr and Abdolhosseini 2011 with a dramatic increase in periodontal disease, suggesting that this AMP has a direct effect on the survival of, or susceptibility to, periodontal pathogens (reviewed in Gorr and Abdolhosseini 2011).…”

“…We previously reviewed >40 AMPs in the oral cavity and organized these into 6 functional categories, based on their reported antimicrobial activities (Gorr 2009;Gorr and Abdolhosseini 2011). We hypothesized that the diverse functional classeswhich include cationic peptides, bacterial agglutination and adhesion, metal ion chelators, peroxidase activity, cell wall activity, and proteolytic inhibitors (Gorr 2009;Gorr and Abdolhosseini 2011)-enhance the antibacterial activity of oral fluids and limit the development of bacterial resistance to endogenous AMPs, although it should be noted that the in vivo function of individual AMPs is not entirely clear and a single AMP may exhibit multiple functions.…”

Proteomic and bioinformatics analysis of human saliva for the dental-risk assessment

“…Similarly, neutrophil defensin-1 exhibits broad-spectrum antimicrobial activity by binding to specific sites on the cell membrane with subsequent release of cellular ATP in the absence of cytolysis [22,23]. The proteins identified in caries-susceptible subjects, like hemoglobin, protein S100-A9, SPLUNC2 and prolactin-inducible protein, may contribute to the host innate immunity in the oral cavity [18,24].…”