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

Reis, Pablo Victor Mendes Dos; Boff, Daiane; Verly, Rodrigo M.; Melo‐Braga, Marcella Nunes; Cortés, María Esperanza; Santos, Daniel Moreira dos; Pimenta, Adriano Monteiro de Castro; Amaral, Flávio Almeida; Resende, Jarbas M.; Lima, Maria Elena de

doi:10.3389/fmicb.2018.00667

Cited by 31 publications

(44 citation statements)

References 63 publications

(76 reference statements)

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“…Scanning microscopy analyses of U-87 MG cells after treatment with the cationic anticancer peptide bacteriocin LS10 demonstrated cell membrane disintegration, similar to our findings (Baindara et al 2017). LyeTx I-b almost perfect helical structure, as observed from NMR data, also suggests that this peptide is prone to act as a membranolytic peptide (Reis et al 2018). Currently, in vitro studies of LyeTx I-b using large unilamellar vesicles (LUVs) measured by biophysical techniques such as isothermal titration calorimetry (ITC), aiming to better explain the nature of such interactions, are being carried out by our group (to be published elsewhere).…”

Section: Discussionsupporting

confidence: 89%

“…The micrographs shown here are representative of three experiments performed in triplicate of glioblastoma multiform, U-87 MG cells as a model to understand the cytotoxic mechanism of LyeTx I-b peptide and evaluate it anticancer potential. This peptide displayed excellent antimicrobial activities in vitro and in vivo (Reis et al 2018). The aggressive nature of this class of tumor and the poor prognosis of patients with GBM underscore the clear requirement for more precise and powerful treatments (Marqus et al 2017).…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…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. In addition, NMR data revealed that LyeTxI-b adopts a slightly curved helical structure, spanning from the second amino acid residue to its amidated C-terminus, without having, however, an obvious amphipathic secondary structure (Reis et al 2018). To demonstrate the anticancer potential of this peptide, we focused on its cytotoxic activity against brain tumor cells, investigating its mechanism of action on glioma cells (U-87 MG), compared to non-tumoral human cells, as well as morphological studies using scanning and electronic microscopy, supported necroptosis as the main mechanism triggered by the peptide.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…In contrast to LyeTx I, the derived peptide LyeTx I b has an acetylated N-terminal and an amino acid deletion, i.e., a His residue in the sixteenth position, as structural modifications. This change evoked a 10-fold increase in bactericidal activity compared to LyeTx I [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Intravitreal injection of the synthetic peptide LyeTx I b, derived from a spider toxin, into the rabbit eye is safe and prevents neovascularization in a chorio-allantoic membrane model

Silva

Paiva

Dourado

et al. 2018

J Venom Anim Toxins Incl Trop Dis

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BackgroundThe great diversity of molecules found in spider venoms include amino acids, polyamines, proteins and peptides, among others. Some of these compounds can interact with different neuronal receptors and ion channels including those present in the ocular system. To study potential toxicity and safety of intravitreal injection in rabbits of LyeTx I b, a synthetic peptide derived from the toxin LyeTx I found in venom from the spider Lycosa eritrognatha and to evaluate the angiogenic activity on a CAM model.MethodsARPE-19 cells were treated with LyeTx I b (0.36; 0.54; 0.72; 2.89; 4.34 or 9.06 μM). In this study, New Zealand rabbits were used. LyeTx I b (2.89 μM) labeled with FITC dissolved in PBS, or only PBS, were injected into vitreous humor. Electroretinogram (ERG) was recorded 1 day before injection and at 7, 14 and 28 days post-injection. Clinical examination of the retina was conducted through tonometer and eye fundus after ERG. Eyes were enucleated and retinas were prepared for histology in order to assess retinal structure. CAMs were exposed to LyeTx I b (0.54; 0.72; 2.17 or 2.89 μM).ResultsARPE-19 cells exposed to LyeTx I b showed cell viability at the same levels of the control. The fluorescence of LyeTx I b labeled with FITC indicated its retinal localization. Our findings indicate ERG responses from rats injected in the eye with LyeTx I b were very similar to the corresponding responses of those animals injected only with vehicle. Clinical examination found no alterations of intraocular pressure or retinal integrity. No histological damage in retinal layers was observed. CAM presented reduced neovascularization when exposed to LyeTx I b.ConclusionsIntravitreal injection of LyeTx I b is safe for use in the rabbit eye and prevents neovascularization in the CAM model, at Bevacizumab levels. These findings support intravitreal LyeTx I b as a good candidate to develop future alternative treatment for the retina in neovascularization diseases.

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N‐terminal acetylation of antimicrobial peptide L163 improves its stability against protease degradation

Yang

et al. 2021

Journal of Peptide Science

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Antimicrobial peptide L163 was computationally designed by our laboratory; L163 is active against multidrug‐resistant (MDR) bacteria but is easily degraded in the plasma and by trypsin. Amino acid substitution, cyclization, and amino‐terminal (N‐terminal) acetylation were performed to obtain L163 analogs with high stability in the plasma and in trypsin solutions. The stability, antimicrobial activity, and biosafety of L163 and its analogs were investigated. Comparison with unmodified L163 indicated that N‐terminal acetylation enhanced the stability against pH, plasma, and trypsin degradation, and phenylalanine (Phe) substitution for leucine (Leu) and cysteine bridge (S–S) cyclization decreased the stability. N‐terminal acetylation also enhanced antimicrobial activity against MDR Streptococcus Sc181, Listeria monocytogenes, and Enterococcus E1478F; did not change the activity against MDR Staphylococcus aureus 9, Staphylococcus sciuri P254, and Staphylococcus aureus RN4220; and decreased the activity against Candida tropicalis, Candida albicans, and Enterococcus faecalis Fbc35. Phe substitution for Leu and S–S cyclization decreased the antimicrobial activity. The negative effect of these modifications was detected against biofilm formation by the tested microbial strains. Comparison of Phe substitution for Leu and S–S cyclization indicated that N‐terminally acetylated L163 (L163‐Ac) is the best candidate. L163‐Ac peptide had the highest antibacterial activity and enhanced tolerance to temperature, pH, plasma, and trypsin and low toxicity.

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

Cited by 31 publications

References 63 publications

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

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

Intravitreal injection of the synthetic peptide LyeTx I b, derived from a spider toxin, into the rabbit eye is safe and prevents neovascularization in a chorio-allantoic membrane model

N‐terminal acetylation of antimicrobial peptide L163 improves its stability against protease degradation

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