Functional characterization of two novel peptides and their analogs identified from the skin secretion of Indosylvirana aurantiaca, an endemic frog species of Western Ghats, India

Shyla, G; Vineethkumar, T. V.; Arun, V.; Divya, M; Thomas, Sabu; George, Sanil

doi:10.1007/s00049-019-00287-z

Cited by 7 publications

(8 citation statements)

References 30 publications

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“…This was consistent with other reports, which suggest that membrane-penetrated peptides may also block the formation of pathogen biofilms [49,50]. C-terminal amidation of the peptides has been reported to enhance its antibiofilm activity [51]. Similarly, in this study, CTP-NH 2 showed better antibiofilm activity than CTP and CTPQ (Figure 9).…”

Section: Discussionsupporting

confidence: 93%

Novel Hybrid Peptide Cathelicidin 2 (1-13)-Thymopentin (TP5) and Its Derived Peptides with Effective Antibacterial, Antibiofilm, and Anti-Adhesion Activities

Guo

Tong

Wang

et al. 2021

IJMS

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The increasing numbers of infections caused by multidrug-resistant (MDR) pathogens highlight the urgent need for new alternatives to conventional antibiotics. Antimicrobial peptides have the potential to be promising alternatives to antibiotics because of their effective bactericidal activity and highly selective toxicity. The present study was conducted to investigate the antibacterial, antibiofilm, and anti-adhesion activities of different CTP peptides (CTP: the original hybrid peptide cathelicidin 2 (1-13)-thymopentin (TP5); CTP-NH2: C-terminal amidated derivative of cathelicidin 2 (1-13)-TP5; CTPQ: glutamine added at the C-terminus of cathelicidin 2 (1-13)-TP5) by determining the minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), propidium iodide uptake, and analysis by scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy). The results showed that CTPs had broad-spectrum antibacterial activity against different gram-positive and gram-negative bacteria, with MICs against the tested strains varying from 2 to 64 μg/mL. CTPs at the MBC (2 × MIC 64 μg/mL) showed strong bactericidal effects on a standard methicillin-resistant Staphylococcus aureus strain ATCC 43300 after co-incubation for 6 h through disruption of the bacterial membrane. In addition, CTPs at 2 × MIC also displayed effective inhibition activity of several S. aureus strains with a 40–90% decrease in biofilm formation by killing the bacteria embedded in the biofilms. CTPs had low cytotoxicity on the intestinal porcine epithelial cell line (IPEC-J2) and could significantly decrease the rate of adhesion of S. aureus ATCC 43300 on IPEC-J2 cells. The current study proved that CTPs have effective antibacterial, antibiofilm, and anti-adhesion activities. Overall, this study contributes to our understanding of the possible antibacterial and antibiofilm mechanisms of CTPs, which might be an effective anti-MDR drug candidate.

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Section: Discussionsupporting

confidence: 93%

Novel Hybrid Peptide Cathelicidin 2 (1-13)-Thymopentin (TP5) and Its Derived Peptides with Effective Antibacterial, Antibiofilm, and Anti-Adhesion Activities

Guo

Tong

Wang

et al. 2021

IJMS

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“…Identi cation of antitumor peptides from the skin secretion of Indosylvirana aurantiaca Skin secretion from Indosylvirana aurantiaca was used to construct a cDNA library by shotgun cloning [20]. The 14 mature peptides identi ed from the frog's skin secretion (Supplementary Table 1) were chemically synthesized to check the antitumor activity.…”

Section: Resultsmentioning

confidence: 99%

“…Hemolytic assays of SSTP1 was carried out as described [20]. Brie y, fresh human RBCs were resuspended in PBS to make 4% (v/v) solution and exposed to serially diluted peptides in PBS at 37°C.…”

Section: Hemolytic Assaymentioning

confidence: 99%

SSTP1, A Host Defense Peptide, Exploits the Immunomodulatory Il6 Pathway to Induce Apoptosis in Cancer Cells

Shyla

Mohan

et al. 2021

Preprint

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Background: The anticancer activities of host defense peptides (HDPs) are mainly attributed to their cell penetrating activity. Accordingly, several approaches based on machine learning, calculating the membrane pore formation ability, have been proposed for the anti-cancer peptide identification. Since the membranolytic activity can lead to nonspecific effects, like hemolysis, the therapeutic application of such molecules is limited. In this context, we considered the immunomodulatory activity of HDPs, which is regulated by specific membrane targets and immunomodulatory pathways in immune cells. As many immunomodulators are aberrantly expressed in cancer cells, the possibility of the activation of an immunomodulatory pathway was investigated for a novel anticancer HDP, SSTP1.Methods: The fourteen mature peptides identified by shotgun cloning from the frog-skin secretions were screened for cytotoxicity in oral cancer cells. The mechanism of action of the selected peptide, SSTP1 was investigated in comparison to its inactive mutant, SSTP2. An RNA-Seq coupled with pathway enrichment analysis was performed to identify the upstream signaling leading to the mitochondrial pathway of apoptosis. Since the activation of the IL6/IL6R pathway was suggested, we performed in silico docking studies to find the binding of SSTP1 to the IL6/IL6Rα/gp130 complex. The dynamic simulation predicted the conformational changes in the active site residues. The confocal co-localization studies, pull-down assay, FRET analysis, western blot and reporter assays were performed to elucidate the role of the IL6/IL6R pathway in SSTP1-induced apoptosis. Specific small molecule inhibitors and neutralizing antibodies were used to ascertain the role of the IL6/IL6Rα/gp130 complex in the activation of JNK/AP1 pathway-dependent cell death.Results: SSTP1, a novel temporin, modulates the IL6 pathway and induces apoptosis when it binds to IL6Rα on the active IL6/IL6Rα/gp130 complex, rearranging the active site residues. In contrast to the IL6 blockers inhibiting JAK/STAT activity, SSTP1 shifts the proliferative IL6/JAK/STAT signaling to the apoptotic IL6/JNK/AP1 pathway. In IL6Rα-overexpressing cancer cells, apoptosis is preferred over the membranolytic activity, upon SSTP1 treatment.Conclusions: Here, we provide the evidence of an HDP-induced signaling through immunomodulators, leading to apoptosis in cancer cells. Our study also implies the importance of identifying the targets of HDPs for their clinical application

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“…C-terminal amidation is one of the most commonly found post-translational modifications in bioactive peptides from different origins [ 1 , 37 ]. It has been reported that amidation results in greater biological activity of peptides, including inhibitory effects against pathogenic bacteria, but also increases deleterious effects such as hemolysis [ 38 ]. Using circular dichroism and molecular dynamics simulations, Mura et al showed that Aurein analogs with C-terminal amidation are more likely to form α-helices than the same peptides in the acidic form [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Figainin 1, a Novel Amphibian Skin Peptide with Antimicrobial and Antiproliferative Properties

et al. 2020

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Amphibian skin secretions are abundant in bioactive compounds, especially antimicrobial peptides. These molecules are generally cationic and rich in hydrophobic amino acids, have an amphipathic structure and adopt an α-helical conformation when in contact with microorganisms membranes. In this work, we purified and characterized Figainin 1, a novel antimicrobial and antiproliferative peptide from the cutaneous secretion of the frog Boana raniceps. Figainin 1 is a cationic peptide with eighteen amino acid residues—rich in leucine and isoleucine, with an amidated C-terminus—and adopts an α-helical conformation in the presence of trifluoroethanol (TFE). It displayed activity against Gram-negative and especially Gram-positive bacteria, with MIC values ranging from 2 to 16 µM, and showed an IC50 value of 15.9 µM against epimastigote forms of T. cruzi; however, Figanin 1 did not show activity against Candida species. This peptide also showed cytolytic effects against human erythrocytes with an HC50 of 10 µM, in addition to antiproliferative activity against cancer cells and murine fibroblasts, with IC50 values ranging from 10.5 to 13.7 µM. Despite its adverse effects on noncancerous cells, Figainin 1 exhibits interesting properties for the development of new anticancer agents and anti-infective drugs against pathogenic microorganisms.

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Functional characterization of two novel peptides and their analogs identified from the skin secretion of Indosylvirana aurantiaca, an endemic frog species of Western Ghats, India

Cited by 7 publications

References 30 publications

Novel Hybrid Peptide Cathelicidin 2 (1-13)-Thymopentin (TP5) and Its Derived Peptides with Effective Antibacterial, Antibiofilm, and Anti-Adhesion Activities

Novel Hybrid Peptide Cathelicidin 2 (1-13)-Thymopentin (TP5) and Its Derived Peptides with Effective Antibacterial, Antibiofilm, and Anti-Adhesion Activities

SSTP1, A Host Defense Peptide, Exploits the Immunomodulatory Il6 Pathway to Induce Apoptosis in Cancer Cells

Figainin 1, a Novel Amphibian Skin Peptide with Antimicrobial and Antiproliferative Properties

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