Antimicrobial and immunomodulatory activity of host defense peptides, clavanins and LL-37, in vitro : An endodontic perspective

Lima, Stella M. F.; Freire, Mirna S.; Gomes, Ana Luisa O.; Cantuária, Ana Paula de Castro; Dutra, Flávia Rodrigues P.; Magalhães, Beatriz Simas; Sousa, Maurício Gonçalves C.; Migliolo, Ludovico; Almeida, Jeeser Alves de; Franco, Octávio L.; Rezende, Taia Maria Berto

doi:10.1016/j.peptides.2017.07.005

Cited by 17 publications

(16 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Propionibacterium acnes is a Gram‐positive bacterium known for its critical role in inducing acne vulgaris, which is partially due to its ability to produce a number of virulence factors including the release of pro‐inflammatory cytokines (Li et al, ). Several peptides possess a dual antimicrobial and immunomodulatory function (Lima et al, ), with modes of action different from currently used antibiotics, a low tendency for bacteria to develop resistance, and, in some cases, fast killing kinetics. We therefore chose AMPs as a tool to develop potent anti‐ P. acnes agents.…”

Section: Discussionmentioning

confidence: 99%

“…*P< .05, compared to control inflammatory cytokines (Li et al, 2015). Several peptides possess a dual antimicrobial and immunomodulatory function (Lima et al, 2017), with modes of action different from currently used antibiotics, a low tendency for bacteria to develop resistance, and, in some cases, fast killing kinetics. We therefore chose AMPs as a tool to develop potent anti-P. acnes agents.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with a dual antibacterial and anti‐inflammatory action

Yang

Wang

et al. 2019

British J Pharmacology

View full text Add to dashboard Cite

Background and Purpose Propionibacterium acnes is a Gram‐positive bacterium associated with the skin disorder acne. In this study, as fatty acids are considered to be important in the life habitat of P. acnes, we tested our lipopeptide library in an attempt to create potent P. acnes‐specific antimicrobial agents. Experimental Approach The antimicrobial activity of various lipopeptides was determined by measuring their minimal inhibitory concentration (MIC). Lipids from P. acnes were used to explore their mode of action. RAW264.7 cells stimulated with LPS and P. acnes respectively were used to measure their anti‐inflammatory activity. Mice ears injected with P. acnes were used to assess the antimicrobial and anti‐inflammatory effects of the peptides tested in vivo. Key Results The most potent candidate, C16‐KWKW, was observed to be more active against P. acnes than against other non‐targeted bacterial strains, such as Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The mode of action of C16‐KWKW was observed to be through interference with the integrity of the bacterial membrane, thereby impairing membrane permeability and causing leakage of inner contents of bacterial cells. Furthermore, C16‐KWKW inhibited the expression of pro‐inflammatory cytokines, such as IL‐1β, TNF‐α, and inducible NOS stimulated by both LPS and P. acnes, thus showing potential anti‐inflammatory activity, which was further verified in the in vivo animal studies. Conclusions and Implications C16‐KWKW is a lipopeptide displaying both anti‐P. acnes and anti‐inflammatory effects in vitro and in vivo and shows potential as a treatment for acne vulgaris induced by P. acnes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with a dual antibacterial and anti‐inflammatory action

Yang

Wang

et al. 2019

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…These immunomodulatory properties can include LPS-/LTA-binding ability and subsequent dampening of TLR-mediated proinflammatory responses. Indeed, the multifunctionality of antimicrobial peptides in the clearance of infection and in modulating inflammation points to their therapeutic usefulness in endodontic therapies 33 . Although data are limited on the regenerative effects of antimicrobial peptides, LL-37 has been shown to be biocompatible with dental pulp stem cells in vitro and has been suggested as a possible adjunct for their enhanced proliferation and differentiation 66 .…”

Section: Discussionmentioning

confidence: 99%

“…Using SYTOX green permeabilization assays, the antimicrobial activity was shown to be associated with membrane perturbation effects 32 . LL-37 has also been shown to be efficacious against E. faecalis in planktonic form 33 . Furthermore, when LL-37 was complexed with the glycosaminoglycan heparin, it retained antimicrobial activity against oral bacteria including S. mutans, Streptococcus sobrinus, Streptococcus salivarius, and Aggregatibacter actinomycetemcomitans, with decreased cytotoxic effects against dental pulp cells.…”

Section: Recruited Inflammatory Cells: Neutrophilsmentioning

confidence: 99%

Natural Antimicrobials in the Dental Pulp

Lundy¹,

Irwin

McLean³

et al. 2020

Journal of Endodontics

View full text Add to dashboard Cite

Introduction: Like many tissues, the dental pulp is equipped with innate and adaptive immune responses, designed to defend against infection and limit its spread. The pulp's innate immune response includes the synthesis and release of antimicrobial peptides by several dental pulp cell types. These naturally-occurring antimicrobial peptides have broad spectrum activity against bacteria, fungi and viruses. There is a resurgence of interest in the bioactivities of naturally-occurring antimicrobial peptides, largely driven by the need to develop alternatives to antibiotics. Methods: This narrative review focused on the general properties of antimicrobial peptides, providing an overview of their sources and actions within the dental pulp. Results: We summarized the relevance of antimicrobial peptides in defending the dental pulp, highlighting the potential for many of these antimicrobials to be modified or mimicked for prospective therapeutic use. Conclusion: Antimicrobial peptides and novel peptide-based therapeutics are particularly attractive as emerging treatments for polymicrobial infections, such as endodontic infections, because of their broad activity against a range of pathogens.

show abstract

“…Nisin, a natural antimicrobial peptide produced by Lactococcus lactis , has been reported to be effective at inhibiting E. faecalis biofilms when employed as an experimental intracanal dressing for 1 week, whilst complete elimination of E. faecalis was not observed (Arias‐Moliz et al 2015, Somanath et al 2015). A recent study evaluated the antimicrobial activity of several host defence peptides (clavanin A, clavanin A modified and LL‐37) and found E. faecalis was susceptible only to LL‐37, which inhibited E. faecalis growth at a high concentration of 256.0 mg L −1 (Lima et al 2017). Another study reported that HBD3‐C15, a synthetic peptide consisting of 15 amino acids from the C‐terminus of human β‐defensin‐3, had an inhibitory effect on biofilm formation by E. faecalis on human dentine blocks for 24 h, and more effective results were observed when used in combination with CHX or calcium hydroxide (Ahn et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial peptide GH12 as root canal irrigant inhibits biofilm and virulence of Enterococcus faecalis

Wang

Chen

et al. 2020

Int Endodontic J

View full text Add to dashboard Cite

Aim The objectives of this laboratory‐based study were to investigate the effects of GH12 on Enterococcus faecalis biofilm and virulence. Methodology Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of GH12 against E. faecalis were first determined. A time‐kill assay was further conducted. The effects of GH12 on the expression of virulence and stress genes in E. faecalis were evaluated by RT‐qPCR. Crystal violet stain was used to investigate the effects of GH12 on E. faecalis biofilm formation and 1‐day‐old biofilm. Finally, an ex vivo tooth model contaminated with E. faecalis was used to evaluate the antimicrobial activity of GH12 as an irrigant by CFU counting, SEM and CLSM. One‐way anova and Tukey’s multiple comparisons test were used to compare the differences amongst groups (α = 0.05). Results The MICs and MBCs of GH12 against E. faecalis were 8.0 ± 0.0 and 16.0 ± 0.0 mg L−1, respectively, and GH12 at 32.0 mg L−1 reduced the bacterial numbers by more than 99.9% within 1 min. Various virulence genes (efaA, esp and gelE) and stress genes (dnaK, groEL, ctsR and clpPBCEX) in E. faecalis were significantly downregulated by GH12 at sub‐MIC levels (P < 0.05). Additionally, both E. faecalis biofilm formation and the biomass of 1‐day‐old E. faecalis biofilm were significantly reduced by GH12 (P < 0.05). Elimination of E. faecalis in biofilms from root canal walls was achieved through irrigation with 64.0 mg L−1 GH12 for 30 min. CLSM analysis revealed that GH12 at 64.0 mg L−1 was most effective in eliminating bacteria within dentinal tubules (P < 0.05). Conclusion In a laboratory setting, and when used as an irrigant, GH12 suppressed E. faecalis, downregulated specific virulence and stress‐associated genes, eliminated intracanal E. faecalis protected by biofilms and killed bacteria in dentinal tubules. These results emphasize the need for preclinical and clinical studies to explore the potential of GH12 as an antimicrobial agent during root canal treatment.

show abstract

Antimicrobial and immunomodulatory activity of host defense peptides, clavanins and LL-37, in vitro : An endodontic perspective

Cited by 17 publications

References 58 publications

Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with a dual antibacterial and anti‐inflammatory action

Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with a dual antibacterial and anti‐inflammatory action

Natural Antimicrobials in the Dental Pulp

Antimicrobial peptide GH12 as root canal irrigant inhibits biofilm and virulence of Enterococcus faecalis

Contact Info

Product

Resources

About