Abstract
The development of the oral biofilm requires a complex series of interactions between host tissues and the colonizing bacteria as well as numerous interspecies interactions between the organisms themselves. Disruption of normal host–microbe homoeostasis in the oral cavity can lead to a dysbiotic microbial community that contributes to caries or periodontal disease. A variety of approaches have been pursued to develop novel potential therapeutics that are active against the oral biofilm and/or target specific oral bacteria. The structure and function of naturally occurring antimicrobial peptides from oral tissues and secretions as well as external sources such as frog skin secretions have been exploited to develop numerous peptide mimetics and small molecule peptidomimetics that show improved antimicrobial activity, increased stability and other desirable characteristics relative to the parent peptides. In addition, a rational and minimalist approach has been developed to design small artificial peptides with amphipathic α‐helical properties that exhibit potent antibacterial activity. Furthermore, with an increased understanding of the molecular mechanisms of beneficial and/or antagonistic interspecies interactions that contribute to the formation of the oral biofilm, new potential targets for therapeutic intervention have been identified and both peptide‐based and small molecule mimetics have been developed that target these key components. Many of these mimetics have shown promising results in in vitro and pre‐clinical testing and the initial clinical evaluation of several novel compounds has demonstrated their utility in humans.
Highlights
Periodontal diseases and dental caries are the most common bio‐ film‐mediated diseases of the oral cavity in both developing and de‐ veloped countries
To determine if anti‐biofilm activity occurred with biofilms growing on other mate‐ rial surfaces that may be present in the oral cavity, the activity of DJK5 and innate defence regulator (IDR)‐1018 peptides against biofilms grown on hydroxy‐ apatite and titanium surfaces was compared
The current hypothesis that oral disease arises from the disruption of normal host–microbe ho‐ moeostasis suggests that targeting specific organisms that initiate or promote the formation of dysbiotic communities may represent a viable and effective therapeutic strategy
Summary
Periodontal diseases and dental caries are the most common bio‐ film‐mediated diseases of the oral cavity in both developing and de‐ veloped countries. Consistent with the prior activ‐ ity profile of IDR‐1018, neither SHABP nor MHABP inhibited the growth of planktonic supragingival cultures Both peptides signifi‐ cantly reduced biofilm biovolume and increased killing of biofilm cells upon both short‐ (3–9 min) and long‐term (1–3 days) expo‐ sure (Yang et al, 2019), SHABP was more effective than. The peptide ex‐ hibited bactericidal activity against Gram‐positive organisms but was weakly active against Gram‐negative bacteria and like many natural antimicrobial peptides, temporin‐1CEb exhibited significant haemolytic activity To counter these limitations, Shang, Li, et al (2012) and Shang, Sun, Wang, Wei, and Sun (2012) designed sev‐ eral temporin‐1CEb analogues with increased cationic character and decreased hydrophobicity by substituting Lys residues for neutral and/or non‐polar amino acids of the peptide. C16G2 SAPP B BAR peptide combinatorial N1182 combinatorial T1184 combinatorial V1185 CR‐BAR
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