Antibacterial Effect of Synthetic Peptide LyeTxI and LyeTxI/β‐Cyclodextrin Association Compound Against Planktonic and Multispecies Biofilms of Periodontal Pathogens

Olivo, Edison Andrés Cruz; Santos, Daniel Moreira dos; Lima, Maria Elena de; Santos, Vera Lúcia dos; Sinisterra, Rubén D.; Cortés, María Esperanza

doi:10.1902/jop.2016.160438

Cited by 15 publications

(8 citation statements)

References 44 publications

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“…Moreover, this peptide inhibits periodontal pathogens and epithelial cells proliferation ( Consuegra et al, 2013 ). Recently, our group showed that LyeTxI and its formulation in beta-cyclodextrin, besides being active against periodontopathic bacteria, can also be used to prevent biofilm development ( Cruz Olivo et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

LyeTxI-b, a Synthetic Peptide Derived From Lycosa erythrognatha Spider Venom, Shows Potent Antibiotic Activity in Vitro and in Vivo

et al. 2018

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The antimicrobial peptide LyeTxI isolated from the venom of the spider Lycosa erythrognatha is a potential model to develop new antibiotics against bacteria and fungi. In this work, we studied a peptide derived from LyeTxI, named LyeTxI-b, and characterized its structural profile and its in vitro and in vivo antimicrobial activities. Compared to LyeTxI, LyeTxI-b has an acetylated N-terminal and a deletion of a His residue, as structural modifications. The secondary structure of LyeTxI-b is a well-defined helical segment, from the second amino acid to the amidated C-terminal, with no clear partition between hydrophobic and hydrophilic faces. Moreover, LyeTxI-b shows a potent antimicrobial activity against Gram-positive and Gram-negative planktonic bacteria, being 10-fold more active than the native peptide against Escherichia coli. LyeTxI-b was also active in an in vivo model of septic arthritis, reducing the number of bacteria load, the migration of immune cells, the level of IL-1β cytokine and CXCL1 chemokine, as well as preventing cartilage damage. Our results show that LyeTxI-b is a potential therapeutic model for the development of new antibiotics against Gram-positive and Gram-negative bacteria.

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Section: Introductionmentioning

confidence: 99%

LyeTxI-b, a Synthetic Peptide Derived From Lycosa erythrognatha Spider Venom, Shows Potent Antibiotic Activity in Vitro and in Vivo

et al. 2018

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“…In this context, we synthetized a cationic peptide, LyeTx I-b, based on a peptide isolated from the venom of Lycosa erythrognatha spider. This peptide showed strong antimicrobial activity against Gram-positive and negative bacteria including planktonic and multispecies biofilms of periodontal pathogens under various conditions with slight hemolytic activity (Santos et al 2010;Reis et al 2018;Cruz Olivo et al 2017). LyeTxI-b is a synthetic 24-mer peptide (IWL-TALKFLGKNLGKLAKQQLAKL-NH2), which comprises a His16 deletion and N-terminal acetylation, resulting in an improved effect against resistant bacteria.…”

Section: Introductionmentioning

confidence: 99%

The synthetic peptide LyeTxI-b derived from Lycosa erythrognatha spider venom is cytotoxic to U-87 MG glioblastoma cells

et al. 2018

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Antimicrobial peptides present a broad spectrum of therapeutic applications, including their use as anticancer peptides. These peptides have as target microbial, normal, and cancerous cells. The oncological properties of these peptides may occur by membranolytic mechanisms or non-membranolytics. In this work, we demonstrate for the first time the cytotoxic effects of the cationic alpha-helical antimicrobial peptide LyeTx I-b on glioblastoma lineage U87-MG. The anticancer property of this peptide was associated with a membranolytic mechanism. Loss of membrane integrity occurred after incubation with the peptide for 15 min, as shown by trypan blue uptake, reduction of calcein-AM conversion, and LDH release. Morphological studies using scanning electron microscopy demonstrated disruption of the plasma membrane from cells treated with LyeTx I-b, including the formation of holes or pores. Transmission electron microscopy analyses showed swollen nuclei with mild DNA condensation, cell volume increase with an electron-lucent cytoplasm and organelle vacuolization, but without the rupture of nuclear or plasmatic membranes. Morphometric analyses revealed a high percentage of cells in necroptosis stages, followed by necrosis and apoptosis at lower levels. Necrostatin-1, a known inhibitor of necroptosis, partially protected the cells from the toxicity of the peptide in a concentration-dependent manner. Imaging flow cytometry confirmed that 59% of the cells underwent necroptosis after 3-h incubation with the peptide. It is noteworthy that LyeTx I-b showed only mild cytotoxicity against normal fibroblasts of human and monkey cell lines and low hemolytic activity in human erythrocytes. All data together point out the anticancer potential of this peptide.

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“…8 Beyond that, LyeTx I alone and 1:1 LyeTx I/β-cyclodextrin inclusion compound are effective against periodontal pathogens with rapid bactericidal effect and capable to reduce metabolic activity of planktonic and 2-day multispecies biofilm cells at concentrations <250 µg·mL −1 . 9,10 Further studies suggested that LyeTx I amino-terminal side is indispensable to the secondary structure conformation of the peptide, influencing its interaction with bacteria, once either the modification of LyeTx I carboxyl-terminal side (LyeTx I-K-HYNIC) or the suppression of a histidine residue in the same portion (LyeTx I-b) does not compromise its antimicrobial activity. 11,12 Recently, LyeTx I-b was formulated with carboxymethylcellulose and showed activity against a strain of Staphylococcus aureus resistant to penicillin, erythromycin, and ampicillin, acting in planktonic condition and reducing biofilm viability in 90%.…”

Section: Introductionmentioning

confidence: 99%

Shortened derivatives from native antimicrobial peptide LyeTx I: In vitro and in vivo biological activity assessment

Fuscaldi

Júnior

Santos

et al. 2020

Exp Biol Med (Maywood)

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In the continuing search for novel antibiotics, antimicrobial peptides are promising molecules, due to different mechanisms of action compared to classic antibiotics and to their selectivity for interaction with microorganism cells rather than with mammalian cells. Previously, our research group has isolated the antimicrobial peptide LyeTx I from the venom of the spider Lycosa erythrognatha. Here, we proposed to synthesize three novel shortened derivatives from LyeTx I (LyeTx I mn; LyeTx I mnΔK; LyeTx I mnΔKAc) and to evaluate their toxicity and biological activity as potential antimicrobial agents. Peptides were synthetized by Fmoc strategy and circular dichroism analysis was performed, showing that the three novel shortened derivatives may present membranolytic activity, like the original LyeTx I, once they folded as an alpha helix in 2.2.2-trifluorethanol and sodium dodecyl sulfate. In vitro assays revealed that the shortened derivative LyeTx I mnΔK presents the best score between antimicrobial (↓ MIC) and hemolytic (↑ EC50) activities among the synthetized shortened derivatives, and LUHMES cell-based NeuriTox test showed that it is less neurotoxic than the original LyeTx I (EC50 [LyeTx I mnΔK] ⋙ EC50 [LyeTx I]). In vivo data, obtained in a mouse model of septic arthritis induced by Staphylococcus aureus, showed that LyeTx I mnΔK is able to reduce infection, as demonstrated by bacterial recovery assay (∼10-fold reduction) and scintigraphic imaging (less technetium-99m labeled-Ceftizoxime uptake by infectious site). Infection reduction led to inflammatory process and pain decreases, as shown by immune cells recruitment reduction and threshold nociception increment, when compared to positive control group. Therefore, among the three shortened peptide derivatives, LyeTx I mnΔK is the best candidate as antimicrobial agent, due to its smaller amino acid sequence and toxicity, and its greater biological activity.

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Antibacterial Effect of Synthetic Peptide LyeTxI and LyeTxI/β‐Cyclodextrin Association Compound Against Planktonic and Multispecies Biofilms of Periodontal Pathogens

Abstract: LyeTxI and LyeTxI/βCD are active against periodontopathic bacteria, showing rapid bactericidal effect and may be used to prevent biofilm development. In the future, AMPs could be therapeutic tools for treatment of periodontitis.

Cited by 15 publications

References 44 publications

LyeTxI-b, a Synthetic Peptide Derived From Lycosa erythrognatha Spider Venom, Shows Potent Antibiotic Activity in Vitro and in Vivo

LyeTxI-b, a Synthetic Peptide Derived From Lycosa erythrognatha Spider Venom, Shows Potent Antibiotic Activity in Vitro and in Vivo

The synthetic peptide LyeTxI-b derived from Lycosa erythrognatha spider venom is cytotoxic to U-87 MG glioblastoma cells

Shortened derivatives from native antimicrobial peptide LyeTx I: In vitro and in vivo biological activity assessment

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