Peptide and non‐peptide mimetics as potential therapeutics targeting oral bacteria and oral biofilms

Sztukowska, Maryta; Roky, Mohammad; Demuth, Donald R.

doi:10.1111/omi.12267

Cited by 21 publications

(21 citation statements)

References 105 publications

(133 reference statements)

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“…Efforts have been made to design novel specifically targeted multi-domain AMPs composed of a species-targeting peptide linked to a broad-spectrum antimicrobial killing peptide domain (Sztukowska et al, 2019). C16G2 is one of the first functional specifically targeted AMPs designed by fusion of a 16−mer region of the Streptococcus mutans competence−stimulating peptide (CSP) as the targeting domain, flexible triglycine linker and G2 AMP, a 16−residue fragment of novispirin G10 (Steinstraesser et al, 2002), and a derivative of ovispirin-1 (N-terminal 18 residues of the sheep cathelicidin SMAP29).…”

Section: Antimicrobial Peptidesmentioning

confidence: 99%

Natural Anti-biofilm Agents: Strategies to Control Biofilm-Forming Pathogens

Mishra¹,

Panda²,

et al. 2020

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Pathogenic microorganisms and their chronic pathogenicity are significant concerns in biomedical research. Biofilm-linked persistent infections are not easy to treat due to resident multidrug-resistant microbes. Low efficiency of various treatments and in vivo toxicity of available antibiotics drive the researchers toward the discovery of many effective natural anti-biofilm agents. Natural extracts and natural product-based antibiofilm agents are more efficient than the chemically synthesized counterparts with lesser side effects. The present review primarily focuses on various natural anti-biofilm agents, i.e., phytochemicals, biosurfactants, antimicrobial peptides, and microbial enzymes along with their sources, mechanism of action via interfering in the quorum-sensing pathways, disruption of extracellular polymeric substance, adhesion mechanism, and their inhibitory concentrations existing in literature so far. This study provides a better understanding that a particular natural anti-biofilm molecule exhibits a different mode of actions and biofilm inhibitory activity against more than one pathogenic species. This information can be exploited further to improve the therapeutic strategy by a combination of more than one natural anti-biofilm compounds from diverse sources.

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Section: Antimicrobial Peptidesmentioning

confidence: 99%

Natural Anti-biofilm Agents: Strategies to Control Biofilm-Forming Pathogens

Mishra¹,

Panda²,

et al. 2020

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“…This interaction has been shown to modulate the virulence potential of P. gingivalis (Hajishengallis & Lamont, ; Kuboniwa & Lamont, ) and may also be important for initial colonization of the oral cavity by P. gingivalis . Therefore, disruption of heterotypic community formation by targeting the Mfa1/antigen I/II interaction may represent a potential therapeutic approach to control P. gingivalis colonization and virulence (Daep et al, ; Sztukowska, Roky, & Demuth, ; Tan et al, ). The region of antigen I/II involved in the interaction with Mfa1 has been extensively characterized (Daep, James, Lamont, & Demuth, ; Daep et al, , ; Daep, Novak, Lamont, & Demuth, ) and these studies led to the development of both peptide and small molecule peptidomimetics that potently inhibit P. gingivalis /streptococcal adherence in vitro and significantly reduced P. gingivalis virulence in vivo (Daep et al, ; Patil et al, ; Patil, Tan, Demuth, & Luzzio, ; Tan et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, disruption of heterotypic community formation by targeting the Mfa1/antigen I/II interaction may represent a potential therapeutic approach to control P. gingivalis colonization and virulence (Daep et al, 2011;Sztukowska, Roky, & Demuth, 2019;Tan et al, 2018). The region of antigen I/II involved in the interaction with F I G U R E 3 (a) Three-dimensional structure of the Mfa1 with a composite of five peptidomimetic adherence inhibitory compounds docked in a putative binding cleft.…”

Section: Discussionmentioning

confidence: 99%

Identification of functional domains of the minor fimbrial antigen involved in the interaction of Porphyromonas gingivalis with oral streptococci

Roky

Trent

Demuth

2020

Molecular Oral Microbiology

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Porphyromonas gingivalis is associated with chronic periodontitis and may initially colonize the oral cavity by adhering to streptococci. Adhesion to streptococci is driven by interaction of the minor fimbrial antigen (Mfa1) with streptococcal antigen I/II. We identified the region of antigen I/II required for this interaction and developed small molecule mimetics that inhibited P. gingivalis adherence. However, the functional motifs of Mfa1 involved in the interaction with antigen I/II remain uncharacterized. A series of N‐ and C‐terminal peptide fragments of Mfa1 were expressed and tested for inhibition of P. gingivalis adherence to S. gordonii. This approach identified residues 225–400 of Mfa1 as essential for P. gingivalis adherence. Using the three‐dimensional structure of Mfa1, a putative binding cleft was identified using SiteMap and five small molecule mimetics could dock in this site. Site‐specific mutation of residues in the predicted cleft, including R240A, W275A, D321A and A357P inhibited the interaction of Mfa1 with streptococci, whereas mutation of residues not in the predicted cleft (V238A, I252F and ΔK253) had no effect. Complementation of an Mfa1‐deficient P. gingivalis strain with wild‐type mfa1 restored adherence to streptococci, whereas complementation with full‐length mfa1 containing the R240A or A357P mutations did not restore adherence. The mutations did not affect polymerization of Mfa1, suggesting that the complemented strains produced intact minor fimbriae. These results identified specific residues and structural motifs required for the Mfa1‐antigen I/II interaction and will facilitate the design of small molecule therapeutics to prevent P. gingivalis colonization of the oral cavity.

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“…Using these AMPs in the MIC level could induce cytotoxic effects by damaging the surrounding tissues. Additionally, AMPs are susceptible to degradation by oral microbes, which may limit the long-term activity of such peptide [ 29 ].…”

Section: Types Of Available Antibacterial Strategiesmentioning

confidence: 99%

Emerging Contact-Killing Antibacterial Strategies for Developing Anti-Biofilm Dental Polymeric Restorative Materials

et al. 2020

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Polymeric materials are the first choice for restoring tooth cavities, bonding tooth-colored fillings, sealing root canal systems, and many other dental restorative applications. However, polymeric materials are highly susceptible to bacterial attachment and colonization, leading to dental diseases. Many approaches have been investigated to minimize the formation of biofilms over polymeric restorative materials and at the tooth/material interfaces. Among them, contact-killing compounds have shown promising results to inhibit dental biofilms. Contact-killing compounds can be immobilized within the polymer structure, delivering a long-lasting effect with no leaching or release, thus providing advantages compared to release-based materials. This review discusses cutting-edge research on the development of contact-killing compounds in dental restorative materials to target oral pathogens. Contact-killing compounds in resin composite restorations, dental adhesives, root canal sealers, denture-based materials, and crown cements have all demonstrated promising antibacterial properties. Contact-killing restorative materials have been found to effectively inhibit the growth and activities of several oral pathogens related to dental caries, periodontal diseases, endodontic, and fungal infections. Further laboratory optimization and clinical trials using translational models are needed to confirm the clinical applicability of this new generation of contact-killing dental restorative materials.

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Peptide and non‐peptide mimetics as potential therapeutics targeting oral bacteria and oral biofilms

Cited by 21 publications

References 105 publications

Natural Anti-biofilm Agents: Strategies to Control Biofilm-Forming Pathogens

Natural Anti-biofilm Agents: Strategies to Control Biofilm-Forming Pathogens

Identification of functional domains of the minor fimbrial antigen involved in the interaction of Porphyromonas gingivalis with oral streptococci

Emerging Contact-Killing Antibacterial Strategies for Developing Anti-Biofilm Dental Polymeric Restorative Materials

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