The Experts below are selected from a list of 522 Experts worldwide ranked by ideXlab platform
Mohamed Amiche - One of the best experts on this subject based on the ideXlab platform.
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Dermaseptins, Multifunctional Antimicrobial Peptides: A Review of Their Pharmacology, Effectivity, Mechanism of Action, and Possible Future Directions
Frontiers in Pharmacology, 2019Co-Authors: Emiel Bartels, Douwe Dekker, Mohamed AmicheAbstract:Dermaseptins are a group of α-helical shaped polycationic peptides isolated from the Hylid frogs, with antimicrobial effects against bacteria, parasites, protozoa, viruses in vitro. Besides, anti-tumor effects have been demonstrated. However, few animal experiments and no clinical trials have been conducted thus far. This review summarizes the current knowledge on the pharmacology, ethno pharmacology, effectivity against infectious pathogens and tumors cells and the mechanism of action of the Dermaseptins. Future research should focus on further clarification of the mechanisms of action, the effectivity of Dermaseptins against several cancer cell lines and their applicability in humans.
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Antitumor and angiostatic activities of the antimicrobial peptide Dermaseptin B2. PLoS One 7
2012Co-Authors: Hanneke Van Zoggel, Yamina Hamma-kourbali, Gilles Carpentier, José Courty, Célia Dos Santos, Mohamed AmicheAbstract:Recently, we have found that the skin secretions of the Amazonian tree frog Phyllomedusa bicolor contains molecules with antitumor and angiostatic activities and identified one of them as the antimicrobial peptide Dermaseptin (Drs) B2. In the present study we further explored the in vitro and in vivo antitumor activity of this molecule and investigated its mechanism of action. We showed that Drs B2 inhibits the proliferation and colony formation of various human tumor cell types, and the proliferation and capillary formation of endothelial cells in vitro. Furthermore, Drs B2 inhibited tumor growth of the human prostate adenocarcinoma cell line PC3 in a xenograft model in vivo. Research on the mechanism of action of Drs B2 on tumor PC3 cells demonstrated a rapid increasing amount of cytosolic lactate dehydrogenase, no activation of caspase-3, and no changes in mitochondrial membrane potential. Confocal microscopy analysis revealed that Drs B2 can interact with the tumor cell surface, aggregate and penetrate the cells. These data together indicate that Drs B2 does not act by apoptosis but possibly by necrosis. In conclusion, Drs B2 could be considered as an interesting and promising pharmacological and therapeutic leader molecule for the treatment of cancer
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Dermaseptin s9 an α helical antimicrobial peptide with a hydrophobic core and cationic termini
Biochemistry, 2006Co-Authors: Olivier Lequin, Pierre Nicolas, Ali Ladram, Ludovic Chabbert, Francine Bruston, Odile Convert, Damien Vanhoye, Gerard Chassaing, Mohamed AmicheAbstract:The Dermaseptins S are closely related peptides with broad-spectrum antibacterial activity that are produced by the skin of the South American hylid frog, Phyllomedusa sauvagei. These peptides are polycationic (Lys-rich), α-helical, and amphipathic, with their polar/charged and apolar amino acids on opposing faces along the long axis of the helix cylinder. The amphipathic α-helical structure is believed to enable the peptides to interact with membrane bilayers, leading to permeation and disruption of the target cell. We have identified new members of the Dermaseptin S family that do not resemble any of the naturally occurring antimicrobial peptides characterized to date. One of these peptides, designated Dermaseptin S9, GLRSKIWLWVLLMIWQESNKFKKM, has a tripartite structure that includes a hydrophobic core sequence encompassing residues 6−15 (mean hydrophobicity, +4.40, determined by the Liu−Deber scale) flanked at both termini by cationic and polar residues. This structure is reminiscent of that of synthet...
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peptide secretion in the cutaneous glands of south american tree frog phyllomedusa bicolor an ultrastructural study
European Journal of Cell Biology, 2000Co-Authors: Claire Lacombe, Pierre Nicolas, Irene Dunia, Carmen Cifuentesdiaz, Michele Auberthomay, Mohamed AmicheAbstract:Summary The development of the dermal glands of the arboreal frog Phyllomedusa bicolor was investigated by immunocytochemistry and electron microscopy. The 3 types of glands (mucous, lipid and serous) differed in size and secretory activity. The mucous and serous glands were apparent in the tadpole skin, whereas the lipid glands developed later in ontogenesis. The peptide antibiotics Dermaseptins and the D-amino acid-containing peptide opioids dermorphins and deltorphins are abundant in the skin secretions of P. bicolor . Although these peptides differ in their structure and activity they are derived from precursors that have very similar preproregions. We used an antibody to the common preproregion of preproDermaseptins and preprodeltorphins and immunofluorescence analysis to show that only the serous glands are specifically involved in the biosynthesis and secretion of Dermaseptins and deltorphins. Scanning and transmission electron microscopy revealed that the serous glands of P. bicolor have morphological features, especially the secretory granules, which differ from those of the glands in Xenopus laevis skin.
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phylloxin a novel peptide antibiotic of the Dermaseptin family of antimicrobial opioid peptide precursors
FEBS Journal, 2000Co-Authors: Thierry Nicolas Pierre, Mohamed Amiche, Aura Lia A Seon, Pierre NicolasAbstract:A novel family of peptide precursors that have very similar N-terminal preprosequences followed by markedly different C-terminal domains has been identified in the skin of hylid frogs belonging to the genus Phyllomedusinae. Biologically active peptides derived from the variable domains include the Dermaseptins, 28–34-residue peptides that have a broad-spectrum microbicidal activity, and dermorphin and the deltorphins, d-amino acid containing heptapeptides that are very potent agonists for the µ-opioid and δ-opioid receptors, respectively. This report describes the isolation, synthesis and cloning of phylloxin, a prototypical member of a novel family of antimicrobial peptides derived from the processing of a Dermaseptin/dermorphin-like precursor. The structure of phylloxin (GWMSKIASGIGTFLSGIQQ amide) shows no homology to the Dermaseptins, but bears some resemblance to the levitide-precursor fragment and the xenopsin-precursor fragment, two antimicrobial peptides isolated from the skin of an evolutionarily distant frog species, Xenopus laevis. Circular dichroism spectra of phylloxin in low polarity medium, which mimics the lipophilicity of the membrane of target microorganisms, indicated 60–70% α-helical conformation, and predictions of secondary structure suggested that the peptide can be configured as an amphipathic helix spanning residues 1–19. Phylloxin is an addition to the structurally and functionally diverse peptide families encoded by the rapidly evolving C-terminal domains of the dermorphin/Dermaseptin group of precursors.
Tianbao Chen - One of the best experts on this subject based on the ideXlab platform.
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a novel Dermaseptin isolated from the skin secretion of phyllomedusa tarsius and its cationicity enhanced analogue exhibiting effective antimicrobial and anti proliferative activities
Biomolecules, 2019Co-Authors: Miaoran Li, Xinping Xi, Mei Zhou, Tianbao Chen, Xiaoling Chen, James F Burrows, Lei WangAbstract:A novel Dermaseptin peptide, Dermaseptin-PT9 (DPT9), was isolated and identified from Phyllomedusa tarsius by the combination of molecular cloning and LC-MS analysis. Chemically synthesised DPT9 was broadly effective against the tested microorganisms through the disruption of cell membranes and showed weak haemolytic activity towards horse erythrocytes. It also exhibited anti-proliferative effect against various human cancer cells. Moreover, an analogue with enhanced cationicity, K8, 23-DPT9, in which Asp8 and Glu23 were substituted by lysine residues, had a markedly increased antimicrobial effect against all tested microorganisms and disrupted microbial cell membranes. This analogue also showed no haemolysis at its effective antimicrobial concentrations. In addition, K8, 23-DPT9 displayed an enhanced anti-proliferative effect against cancer cells, while displayed weak activity against the normal human cell line, HMEC-1.
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evaluating the bioactivity of a novel antimicrobial and anticancer peptide Dermaseptin ps4 der ps4 from the skin secretion of phyllomedusa sauvagii
Molecules, 2019Co-Authors: Dong Chen, Mei Zhou, Lei Wang, Xiaowei Zhou, Linyuan Huang, Xi Chen, Tianbao ChenAbstract:Dermaseptins belonging to a large family of cationic membrane-disruption antimicrobial peptides display extensive antibacterial and antiproliferative activities depending on a coil-to-helix transition and the specific structural parameters. Herein, a novel Dermaseptin peptide named Der-PS4 was discovered from the skin secretion of the waxy monkey tree frog, Phyllomedusa sauvagii. The complementary DNA (cDNA)-encoding precursor was obtained relying on "shotgun" cloning, and afterwards, a mature peptide amino acid sequence was identified by reverse-phase high performance liquid chromatography (RP-HPLC) and MS/MS. Specimens were chemically synthesized and applied for further functional studies. Structural analysis demonstrated a higher α-helical content in the membrane-mimetic environment compared with that in the ammonium acetate/water circumstance. Der-PS4 displayed a broad spectrum of antimicrobial activities against tested pathogenic microorganisms, however, exhibiting slight membrane-damaging effectiveness towards horse red blood cells. Coincident with the inhibitory activities on pathogens, Der-PS4 also showed considerable biofilm eradicating impact. Also, Der-PS4 penetrated cell membrane in a relative short period under each minimum bactericidal concentration. In addition, Der-PS4 possessed antiproliferative capacity against five cancer cell lines, while presenting slight suppressing effect on human microvascular endothelial, HMEC-1. These findings provide a promising insight for the discovery and development of novel drugs from a natural source.
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biological activities of cationicity enhanced and hydrophobicity optimized analogues of an antimicrobial peptide Dermaseptin ps3 from the skin secretion of phyllomedusa sauvagii
Toxins, 2018Co-Authors: Yining Tan, Mei Zhou, Lei Wang, Hang Fai Kwok, Xiaoling Chen, James F Burrows, Tianbao ChenAbstract:The skin secretions of the subfamily Phyllomedusinae have long been known to contain a number of compounds with antimicrobial potential. Herein, a biosynthetic Dermaseptin-precursor cDNA was obtained from a Phyllomedusa sauvagii skin secretion-derived cDNA library, and thereafter, the presence of the mature peptide, namely Dermaseptin-PS3 (DPS3), was confirmed by LC⁻MS/MS. Moreover, this naturally occurring peptide was utilized to design two analogues, K5, 17-DPS3 (introducing two lysine residues at positions 5 and 17 to replace acidic amino acids) and L10, 11-DPS3 (replacing two neutral amino acids with the hydrophobic amino acid, leucine), improving its cationicity on the polar/unipolar face and hydrophobicity in a highly conserved sequence motif, respectively. The results in regard to the two analogues show that either increasing cationicity, or hydrophobicity, enhance the antimicrobial activity. Also, the latter analogue had an enhanced anticancer activity, with pretreatment of H157 cells with 1 µM L10, 11-DPS3 decreasing viability by approximately 78%, even though this concentration of peptide exhibited no haemolytic effect. However, it must be noted that in comparison to the initial peptide, both analogues demonstrate higher membrane-rupturing capacity towards mammalian red blood cells.
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Discovery of two skin-derived Dermaseptins and design of a TAT-fusion analogue with broad-spectrum antimicrobial activity and low cytotoxicity on healthy cells
'PeerJ', 2018Co-Authors: Haohao Zhu, Mei Zhou, Lei Wang, Xiyan Ding, Roberta Burden, Tianbao ChenAbstract:Two novel peptides belonging to the Dermaseptin family, namely DRS-CA-1 and DRS-DU-1, were encoded from cDNA libraries derived from the skin secretions of Phyllomedusa camba and Callimedusa (Phyllomedusa) duellmani. Both natural peptides are highly-conserved and exhibited high potency against wild-type Gram-positive, Gram-negative bacteria, yeast and antibiotic-resistant bacteria (MRSA and Pseudomonas aeruginosa) (MICs 4–8 µM) with no obvious hemolytic activity. Collectively these results suggest that both peptides may have potential as novel antibiotics. Additionally, DRS-DU-1 exhibited selective cytotoxicity to tumor cells. The truncated analogue, DP-1 and TAT-fused DP-1 (namely DP-2) were subsequently synthesised. It showed that DP-1 had low antimicrobial activity, no hemolytic and cytotoxicity to tumor cells. However, DP-2 possessed strong antimicrobial activity and the similar selective, no obvious hemolytic activity and cytotoxicity on normal human cells, but enhanced cytotoxicity to tumor cells of DRS-DU-1. These findings indicate that the N-terminus of the Dermaseptins may contribute to their bioactivity, and that addition of the TAT peptide can improve biological activity. The results provide a new insight for designing novel peptide-based antimicrobial or anticancer agents with low hemolytic activity and cytotoxicity
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Dermaseptin ph a novel peptide with antimicrobial and anticancer activities from the skin secretion of the south american orange legged leaf frog pithecopus phyllomedusa hypochondrialis
Molecules, 2017Co-Authors: Linyuan Huang, Xinping Xi, Tianbao Chen, C Shaw, Lei Wang, Dong Chen, Mei ZhouAbstract:The Dermaseptin peptides, mainly derived from the skin secretions of Hylidae frogs, belong to a superfamily of antimicrobial peptides and exhibit diverse antimicrobial and anticancer activities with low cytotoxicity. Here, we reported a novel Dermaseptin peptide, from the South American orange-legged leaf frogs, Pithecopus (Phyllomedusa) hypochondrialis, processing the shortest peptide length, namely Dermaseptin-PH. The complementary DNA (cDNA) encoding biosynthetic precursor of Dermaseptin-PH was initially identified by the rapid amplification of cDNA ends PCR (RACE-PCR) technique from the skin secretion. The predicted primary structure was confirmed by a combination of reverse-phase high performance liquid chromatography (RP-HPLC) and MS/MS fragmentation from the skin secretion. Chemically-synthetic Dermaseptin-PH was investigated using a range of bioactivity assessment assays to evaluate the biological activities and cytotoxicity of Dermaseptin-PH. Dermaseptin-PH inhibited the growth of Gram-negative bacteria, Gram-positive bacteria, and pathogenic yeast Candida albicans. In addition, Dermaseptin-PH showed a broad-spectrum of anticancer activities against several cancer cell lines including MCF-7, H157, U251MG, MDA-MB-435S, and PC-3. The potent antimicrobial and anticancer activities of Dermaseptin-PH make it a promising candidate in the discovery of new drugs for clinical applications, and the relatively short sequence of Dermaseptin-PH can provide new insight for the research and structural modification of new peptide drugs.
José Roberto S. A. Leite - One of the best experts on this subject based on the ideXlab platform.
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Antiviral activity of Dermaseptin 01 against Dengue virus type 2, Herpes simplex virus type 1 and Vaccinia virus [Abstract in English]
Scientia Medica, 2013Co-Authors: João Luiz Macedo De Souza Cardoso, José Roberto S. A. Leite, Maria José Dos Santos Soares, Luiz Cosme Cotta Malaquias, Luiz Felipe Leomil CoelhoAbstract:AIMS: Determine the in vitro antiviral activity of Dermaseptin-1 an antimicrobial peptide discovered in the skin secretion of Phyllomedusa hypochondrialis frogs against Herpes simplex virus type 1, Vaccinia virus and Dengue virus type 2. METHODS: The Peptide Dermaseptin-1 was used for the cytotoxic assays using Vero, LLCMK2 and C6/36 cells. The antiviral activity was evaluated using (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay for Herpes simplex virus type 1 and Vaccinia virus in VERO cells and for Dengue virus type 2 in LLCMK2 cells. The antiviral activity of Dermaseptin-1was also evaluated in C6/36 cells infected with Dengue virus type 2 by cytopathic effect reduction. RESULTS: The 50% cytotoxicity concentration of Dermaseptin-1 was 105 µg/ml in insect cells (C6/36) and more than 1000 µg/ml in mammalian cells (VERO and LLCMK2). DS-01 displayed antiviral effect only against Dengue virus type 2 with a 50% effective concentration of 15 µg/ml in C6/36 cells and 60 µg/ml in LLCMK2 cells. CONCLUSIONS: These data suggested that Dermaseptin 01 have an in vitro antiviral action against Dengue virus type 2 but not against Herpes simplex virus type 1 or Vaccinia virus .
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in vitro synergistic interaction between amide piplartine and antimicrobial peptide Dermaseptin against schistosoma mansoni schistosomula and adult worms
Current Medicinal Chemistry, 2012Co-Authors: Josue De Moraes, José Roberto S. A. Leite, Katrin Ingram, Claudete Catanhede Do Nascimento, Lydia F Yamaguchi, Clicia Ramos Bittencourt, Marcelo P Bemquerer, Massuo J Kato, Eliana NakanoAbstract:Schistosomiasis is one of the world's major public health problems, and praziquantel is the only available drug to treat this notable neglected disease. Drug combinations have been considered an important strategy for treatment of infectious diseases, which might enhance therapeutic efficacy and delaying resistance. In this study, we have examined the in vitro activities of the amide piplartine and the antimicrobial peptide Dermaseptin 01 administered singly or in combination against Schistosoma mansoni of different ages including 3-hour-old and 7-day-old schistosomula and 49-day-old adult schistosomes as well as on egg output by adult worms. We calculated the median lethal concentrations (LC(50)) of 7.87 and 17.99 μM on 49-day-old adults, 11.02 and 71.58 μM on 7-day-old schistosomula, and 70.87 and 98.42 μM on 3-hour-old schistosomula for piplartine and Dermaseptin, respectively. Most Piplartine/Dermaseptin combinations showed synergistic effect, with combination index (CI) values less than 0.9 when S. mansoni adults or schistosomula were simultaneously incubated with both drugs in vitro; synergy between these two compounds was also indicated using isobolograms. Additionally, we observed alterations on the tegumental surface of schistosomula and adult schistosomes by means of laser scanning confocal microscopy. Furthermore, egg laying of surviving worms was considerably more reduced when exposed to the piplartine/Dermaseptin combinations than each drug alone, and this inhibition was irreversible. This is the first report on the synergistic effect between piplartine and Dermaseptin against S. mansoni and opens the route to further studies (e.g. in vivo) to characterize this combination in greater detail.
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development of a novel biosensor using cationic antimicrobial peptide and nickel phthalocyanine ultrathin films for electrochemical detection of dopamine
International Journal of Analytical Chemistry, 2012Co-Authors: Maysa F Zampa, José Roberto S. A. Leite, Ines M S Araujo, Jose Ribeiro Dos Santos, Valtencir Zucolotto, Carla EirasAbstract:The antimicrobial peptide Dermaseptin 01 (DS 01), from the skin secretion of Phyllomedusa hypochondrialis frogs, was immobilized in nanostructured layered films in conjunction with nickel tetrasulfonated phthalocyanines (NiTsPc), widely used in electronic devices, using layer-by-layer technique. The films were used as a biosensor to detect the presence of dopamine (DA), a neurotransmitter associated with diseases such as Alzheimer's and Parkinson's, with detection limits in the order of 10−6 mol L−1. The use of DS 01 in LbL film generated selectivity in the detection of DA despite the presence of ascorbic acid found in biological fluids. This work is the first to report that the antimicrobial peptide and NiTsPc LbL film exhibits electroanalytical activity to DA oxidation. The selectivity in the detection of DA is a fundamental aspect for the development of electrochemical sensors with potential applications in the biomedical and pharmaceutical industries.
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evaluation of the in vitro activity of Dermaseptin 01 a cationic antimicrobial peptide against schistosoma mansoni
Chemistry & Biodiversity, 2011Co-Authors: José Roberto S. A. Leite, Josue De Moraes, Carlos Nascimento, Leiz M C V Miura, Eliana Nakano, Toshie KawanoAbstract:Schistosomiasis is a neglected tropical disease that remains a considerable public health problem worldwide. Since the mainstay of schistosomiasis control is chemotherapy with a single drug, praziquantel, drug resistance is a concern. Here, we examined the in vitro effects of Dermaseptin 01 (DS 01), an antimicrobial peptide found in the skin secretion of frogs of the genus Phyllomedusa, on Schistosoma mansoni adult worms. DS 01 at a concentration of 100 μg/ml reduced the worm motor activity and caused the death of all worms within 48 h in RPMI 1640 medium. At the highest sublethal concentration of antimicrobial peptide (75 μg/ml), a 100% reduction in egg output of paired female worms was observed. Additionally, DS 01 induced morphological alterations on the tegument of S. mansoni, and a quantitative analysis carried out by confocal microscopy revealed extensive destruction of the tubercles in a dose-dependent manner over the concentration range of 50–200 μg/ml. It was the first time that an anthelmintic activity towards schistosomes has been reported for a Dermaseptin.
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Dermaseptins from phyllomedusa oreades and phyllomedusa distincta secondary structure antimicrobial activity and mammalian cell toxicity
Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2008Co-Authors: Guilherme D Brand, Graciella R Martins, Wilian R C Bento, Antonio L T Araujo, Luciano P. Silva, José Roberto S. A. Leite, Selma Aparecida Souza Kuckelhaus, Andreia M LazzariAbstract:Abstract The present study reports the structural characteristics, the biological activities, and preliminary clinical investigations of three synthetic members of the Dermaseptin family of antimicrobial peptides. The three peptides showed similar tendencies to form α-helical structures in non-polar media. The antimicrobial activity towards bacteria and fungi was determined in the micromolar concentration and the peptides did not influenced peritoneal cells viability. One of the peptides was intravenously administered in mice at concentrations similar to those of antibiotics employed in bacterial/fungal infections and it did not cause any detectable changes in cells and tissues.
Peter J Coote - One of the best experts on this subject based on the ideXlab platform.
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an amphibian derived cationic α helical antimicrobial peptide kills yeast by caspase independent but aif dependent programmed cell death
Molecular Microbiology, 2007Co-Authors: Oliver C Morton, Sandra Dos C Santos, Peter J CooteAbstract:Summary The Dermaseptins are a family of antimicrobial peptides from the tree-frog Phyllomedusa sauvagii. Yeast exposed to Dermaseptin S3(1-16), a truncated derivative of Dermaseptin S3 with full activity, showed diagnostic markers of yeast apoptosis: the appearance of reactive oxygen species and fragmentation of nuclear DNA. This process was independent of the yeast caspase, Yca1p. Screening of a non-essential gene deletion collection in yeast identified genes that conferred resistance to Dermaseptin S3(1-16): izh2Δ, izh3Δ, stm1Δ and aif1Δ, all known to be involved in regulating yeast apoptosis. The appearance of apoptotic markers was reduced in these strains when exposed to the peptide. Dermaseptin S3(1-16) was shown to interact with DNA, and cause DNA damage in vivo, a process known to trigger apoptosis. Supporting this, a Dermaseptin S3(1-16) affinity column specifically purified Stm1p, Mre11p and Htb2p; DNA-binding proteins implicated in yeast apoptosis and DNA repair. Thus, amphibians may have evolved a mechanism to induce cell suicide in invading fungal pathogens.
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inhibitory action of a truncated derivative of the amphibian skin peptide Dermaseptin s3 on saccharomyces cerevisiae
Antimicrobial Agents and Chemotherapy, 1998Co-Authors: Peter J Coote, Dudley P. Ferdinando, Caroline D Holyoak, Dani Bracey, James A. PearceAbstract:The inhibitory activity of a truncated derivative of the natural amphibian skin peptide Dermaseptin s3-(1-16)-NH2 [DS s3 (1-16)] against Saccharomyces cerevisiae was studied. Significant growth inhibition was observed after exposure to 3.45 microgram of the peptide per ml at pH 6.0 and 7.0, with complete growth inhibition occurring at 8.63 microgram of peptide per ml for all pH values tested. Using confocal scanning laser microscopy, we have shown that DS s3 (1-16) disrupted the yeast cell membrane resulting in the gross permeabilization of the cell to the nuclear stain ethidium bromide. However, the principal inhibitory action of the peptide was not due to disruption of intracellular pH homeostasis. Instead, growth inhibition by the peptide correlated with the efflux of important cellular constituents such as ADP, ATP, RNA, and DNA into the surrounding medium. The combination of DS s3 (1-16) with mild heating temperatures as low as 35 degreesC significantly enhanced the inhibitory effect of the peptide (8.63 microgram/ml), and at 45 degreesC greater than 99% of the population was killed in 10 min. In summary, a derivative of a natural antimicrobial peptide has potential, either alone or in combination with mild heating, to prevent the growth of or kill spoilage yeast.
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inhibitory action of a truncated derivative of the amphibian skin peptide Dermaseptin s3 on saccharomyces cerevisiae
Antimicrobial Agents and Chemotherapy, 1998Co-Authors: Peter J Coote, Dudley P. Ferdinando, Caroline D Holyoak, Dani Bracey, James A. PearceAbstract:The inhibitory activity of a truncated derivative of the natural amphibian skin peptide Dermaseptin s3-(1-16)-NH 2 [DS s3 (1-16)] against Saccharomyces cerevisiae was studied. Significant growth inhibition was observed after exposure to 3.45 μg of the peptide per ml at pH 6.0 and 7.0, with complete growth inhibition occurring at 8.63 μg of peptide per ml for all pH values tested. Using confocal scanning laser microscopy, we have shown that DS s3 (1-16) disrupted the yeast cell membrane resulting in the gross permeabilization of the cell to the nuclear stain ethidium bromide. However, the principal inhibitory action of the peptide was not due to disruption of intracellular pH homeostasis. Instead, growth inhibition by the peptide correlated with the efflux of important cellular constituents such as ADP, ATP, RNA, and DNA into the surrounding medium. The combination of DS s3 (1-16) with mild heating temperatures as low as 35°C significantly enhanced the inhibitory effect of the peptide (8.63 μg/ml), and at 45°C greater than 99% of the population was killed in 10 min. In summary, a derivative of a natural antimicrobial peptide has potential, either alone or in combination with mild heating, to prevent the growth of or kill spoilage yeast.
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Inhibitory action of a truncated derivative of the amphibian skin peptide Dermaseptin s3 on Saccharomyces cerevisiae." Antimicrobial Agents and Chemotherapy
1998Co-Authors: Peter J Coote, Dudley P. Ferdinando, James A. PearceAbstract:Inhibitory action of a truncated derivative of the amphibian skin peptide Dermaseptin s3 on Saccharomyces cerevisia
Mei Zhou - One of the best experts on this subject based on the ideXlab platform.
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a novel Dermaseptin isolated from the skin secretion of phyllomedusa tarsius and its cationicity enhanced analogue exhibiting effective antimicrobial and anti proliferative activities
Biomolecules, 2019Co-Authors: Miaoran Li, Xinping Xi, Mei Zhou, Tianbao Chen, Xiaoling Chen, James F Burrows, Lei WangAbstract:A novel Dermaseptin peptide, Dermaseptin-PT9 (DPT9), was isolated and identified from Phyllomedusa tarsius by the combination of molecular cloning and LC-MS analysis. Chemically synthesised DPT9 was broadly effective against the tested microorganisms through the disruption of cell membranes and showed weak haemolytic activity towards horse erythrocytes. It also exhibited anti-proliferative effect against various human cancer cells. Moreover, an analogue with enhanced cationicity, K8, 23-DPT9, in which Asp8 and Glu23 were substituted by lysine residues, had a markedly increased antimicrobial effect against all tested microorganisms and disrupted microbial cell membranes. This analogue also showed no haemolysis at its effective antimicrobial concentrations. In addition, K8, 23-DPT9 displayed an enhanced anti-proliferative effect against cancer cells, while displayed weak activity against the normal human cell line, HMEC-1.
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evaluating the bioactivity of a novel antimicrobial and anticancer peptide Dermaseptin ps4 der ps4 from the skin secretion of phyllomedusa sauvagii
Molecules, 2019Co-Authors: Dong Chen, Mei Zhou, Lei Wang, Xiaowei Zhou, Linyuan Huang, Xi Chen, Tianbao ChenAbstract:Dermaseptins belonging to a large family of cationic membrane-disruption antimicrobial peptides display extensive antibacterial and antiproliferative activities depending on a coil-to-helix transition and the specific structural parameters. Herein, a novel Dermaseptin peptide named Der-PS4 was discovered from the skin secretion of the waxy monkey tree frog, Phyllomedusa sauvagii. The complementary DNA (cDNA)-encoding precursor was obtained relying on "shotgun" cloning, and afterwards, a mature peptide amino acid sequence was identified by reverse-phase high performance liquid chromatography (RP-HPLC) and MS/MS. Specimens were chemically synthesized and applied for further functional studies. Structural analysis demonstrated a higher α-helical content in the membrane-mimetic environment compared with that in the ammonium acetate/water circumstance. Der-PS4 displayed a broad spectrum of antimicrobial activities against tested pathogenic microorganisms, however, exhibiting slight membrane-damaging effectiveness towards horse red blood cells. Coincident with the inhibitory activities on pathogens, Der-PS4 also showed considerable biofilm eradicating impact. Also, Der-PS4 penetrated cell membrane in a relative short period under each minimum bactericidal concentration. In addition, Der-PS4 possessed antiproliferative capacity against five cancer cell lines, while presenting slight suppressing effect on human microvascular endothelial, HMEC-1. These findings provide a promising insight for the discovery and development of novel drugs from a natural source.
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biological activities of cationicity enhanced and hydrophobicity optimized analogues of an antimicrobial peptide Dermaseptin ps3 from the skin secretion of phyllomedusa sauvagii
Toxins, 2018Co-Authors: Yining Tan, Mei Zhou, Lei Wang, Hang Fai Kwok, Xiaoling Chen, James F Burrows, Tianbao ChenAbstract:The skin secretions of the subfamily Phyllomedusinae have long been known to contain a number of compounds with antimicrobial potential. Herein, a biosynthetic Dermaseptin-precursor cDNA was obtained from a Phyllomedusa sauvagii skin secretion-derived cDNA library, and thereafter, the presence of the mature peptide, namely Dermaseptin-PS3 (DPS3), was confirmed by LC⁻MS/MS. Moreover, this naturally occurring peptide was utilized to design two analogues, K5, 17-DPS3 (introducing two lysine residues at positions 5 and 17 to replace acidic amino acids) and L10, 11-DPS3 (replacing two neutral amino acids with the hydrophobic amino acid, leucine), improving its cationicity on the polar/unipolar face and hydrophobicity in a highly conserved sequence motif, respectively. The results in regard to the two analogues show that either increasing cationicity, or hydrophobicity, enhance the antimicrobial activity. Also, the latter analogue had an enhanced anticancer activity, with pretreatment of H157 cells with 1 µM L10, 11-DPS3 decreasing viability by approximately 78%, even though this concentration of peptide exhibited no haemolytic effect. However, it must be noted that in comparison to the initial peptide, both analogues demonstrate higher membrane-rupturing capacity towards mammalian red blood cells.
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Discovery of two skin-derived Dermaseptins and design of a TAT-fusion analogue with broad-spectrum antimicrobial activity and low cytotoxicity on healthy cells
'PeerJ', 2018Co-Authors: Haohao Zhu, Mei Zhou, Lei Wang, Xiyan Ding, Roberta Burden, Tianbao ChenAbstract:Two novel peptides belonging to the Dermaseptin family, namely DRS-CA-1 and DRS-DU-1, were encoded from cDNA libraries derived from the skin secretions of Phyllomedusa camba and Callimedusa (Phyllomedusa) duellmani. Both natural peptides are highly-conserved and exhibited high potency against wild-type Gram-positive, Gram-negative bacteria, yeast and antibiotic-resistant bacteria (MRSA and Pseudomonas aeruginosa) (MICs 4–8 µM) with no obvious hemolytic activity. Collectively these results suggest that both peptides may have potential as novel antibiotics. Additionally, DRS-DU-1 exhibited selective cytotoxicity to tumor cells. The truncated analogue, DP-1 and TAT-fused DP-1 (namely DP-2) were subsequently synthesised. It showed that DP-1 had low antimicrobial activity, no hemolytic and cytotoxicity to tumor cells. However, DP-2 possessed strong antimicrobial activity and the similar selective, no obvious hemolytic activity and cytotoxicity on normal human cells, but enhanced cytotoxicity to tumor cells of DRS-DU-1. These findings indicate that the N-terminus of the Dermaseptins may contribute to their bioactivity, and that addition of the TAT peptide can improve biological activity. The results provide a new insight for designing novel peptide-based antimicrobial or anticancer agents with low hemolytic activity and cytotoxicity
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Dermaseptin ph a novel peptide with antimicrobial and anticancer activities from the skin secretion of the south american orange legged leaf frog pithecopus phyllomedusa hypochondrialis
Molecules, 2017Co-Authors: Linyuan Huang, Xinping Xi, Tianbao Chen, C Shaw, Lei Wang, Dong Chen, Mei ZhouAbstract:The Dermaseptin peptides, mainly derived from the skin secretions of Hylidae frogs, belong to a superfamily of antimicrobial peptides and exhibit diverse antimicrobial and anticancer activities with low cytotoxicity. Here, we reported a novel Dermaseptin peptide, from the South American orange-legged leaf frogs, Pithecopus (Phyllomedusa) hypochondrialis, processing the shortest peptide length, namely Dermaseptin-PH. The complementary DNA (cDNA) encoding biosynthetic precursor of Dermaseptin-PH was initially identified by the rapid amplification of cDNA ends PCR (RACE-PCR) technique from the skin secretion. The predicted primary structure was confirmed by a combination of reverse-phase high performance liquid chromatography (RP-HPLC) and MS/MS fragmentation from the skin secretion. Chemically-synthetic Dermaseptin-PH was investigated using a range of bioactivity assessment assays to evaluate the biological activities and cytotoxicity of Dermaseptin-PH. Dermaseptin-PH inhibited the growth of Gram-negative bacteria, Gram-positive bacteria, and pathogenic yeast Candida albicans. In addition, Dermaseptin-PH showed a broad-spectrum of anticancer activities against several cancer cell lines including MCF-7, H157, U251MG, MDA-MB-435S, and PC-3. The potent antimicrobial and anticancer activities of Dermaseptin-PH make it a promising candidate in the discovery of new drugs for clinical applications, and the relatively short sequence of Dermaseptin-PH can provide new insight for the research and structural modification of new peptide drugs.