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Rui Wang - One of the best experts on this subject based on the ideXlab platform.

  • Membrane-Active Action Mode of Polybia-CP, a Novel Antimicrobial Peptide Isolated from the Venom of Polybia paulista
    2016
    Co-Authors: Kairong Wang, Wen Dang, Bangzhi Zhang, Jiexi Yan, Ru Chen, Wei Zhang, Jingjing Song, Rui Wang
    Abstract:

    The extensive use of antibiotics in medicine, the food industry, and agriculture has resulted in the frequent emergence of multi-drug-resistant bacteria, which creates an urgent need for new antibiotics. It is now widely recognized that antimicrobial peptides (AMPs) could play a promising role in fighting multidrug-resistant bacteria. Antimicrobial peptide Polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized Polybia-CP and studied its action mode of anti-bacterial activity. Our results revealed that Polybia-CP has potent antibacterial activity against both Gram-positive and Gram-negative bacteria. The results from both the real bacterial membrane and the in vitromodel membrane showed that Polybia-CP is membrane active and that its action target is the membrane of bacteria. It is difficult for bacteria to develop resistance to poly-bia-CP, which may thus offer a new strategy for defending against resistant bacteria in medicine and the food and farming industries. InMay 2011, an increased number of cases of enterohemorrhagicEscherichia coli (EHEC) infections with severe disease courses and fatalities occurred in Europe, which were caused by EHEC-contaminated food (e.g., vegetables, fruits, or meat). This event caused panic all over the world, for the isolated EHEC is resistant to antibiotics and caused severe economic losses in the agriculture industry. As we know, E. coli, one of the bacillus species, is widel

  • dual antifungal properties of cationic antimicrobial peptides Polybia mpi membrane integrity disruption and inhibition of biofilm formation
    Peptides, 2014
    Co-Authors: Kairong Wang, Wen Dang, Bangzhi Zhang, Yanyan Zhao, Wei Chen, Rui Wang
    Abstract:

    Abstract With the increasing emergence of resistant fungi, the discovery and development of novel antifungal therapeutics were urgently needed. Compared with conventional antibiotics, the limited propensity of AMPs to induce resistance in pathogens has attracted great interest. In the present study, the antifungal activity and its mechanism-of-action of Polybia-MPI, a cationic peptide from the venom of Social wasp Polybia Paulista was investigated. We demonstrated that Polybia-MPI could potently inhibit the growth of Candida albicans (C. albicans) and Candida glabrata (C. glabrata). The 50% inhibitory concentrations (IC50) of Polybia-MPI against cancer cells were much higher than the MICs against the tested C. albicans and C. glabrata cells, indicating that Polybia-MPI had high selectivity between the fungal and mammalian cells. Our results also indicated that membrane disturbance mechanism was involved in the antifungal activity. Furthermore, Polybia-MPI could inhibit the bio film forming of C. glabrata, which was frequently associated with clinically significant biofilm. These results suggest that Polybia-MPI has great advantages in the development of antifungal agents.

  • membrane active action mode of Polybia cp a novel antimicrobial peptide isolated from the venom of Polybia paulista
    Antimicrobial Agents and Chemotherapy, 2012
    Co-Authors: Kairong Wang, Wen Dang, Bangzhi Zhang, Jiexi Yan, Ru Chen, Wei Zhang, Jingjing Song, Rui Wang
    Abstract:

    The extensive use of antibiotics in medicine, the food industry, and agriculture has resulted in the frequent emergence of multidrug-resistant bacteria, which creates an urgent need for new antibiotics. It is now widely recognized that antimicrobial peptides (AMPs) could play a promising role in fighting multidrug-resistant bacteria. Antimicrobial peptide Polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized Polybia-CP and studied its action mode of antibacterial activity. Our results revealed that Polybia-CP has potent antibacterial activity against both Gram-positive and Gram-negative bacteria. The results from both the real bacterial membrane and the in vitro model membrane showed that Polybia-CP is membrane active and that its action target is the membrane of bacteria. It is difficult for bacteria to develop resistance to Polybia-CP, which may thus offer a new strategy for defending against resistant bacteria in medicine and the food and farming industries.

  • novel cytotoxity exhibition mode of Polybia cp a novel antimicrobial peptide from the venom of the social wasp Polybia paulista
    Toxicology, 2011
    Co-Authors: Kairong Wang, Wen Dang, Bangzhi Zhang, Rui Wang, Ru Chen, Wei Zhang, Jingjing Song, Jindao Zhang
    Abstract:

    Abstract Antimicrobial peptide Polybia-CP was purified from the venom of the social wasp Polybia paulista. It has an amphipathic sequence ILGTILGLLKSL-NH2 and possesses potent antimicrobial activity against both Gram-positive and Gram-negative bacteria. In this study we synthesized Polybia-CP, studied its cytotoxity on tumor cells and proposed its possible mechanism. Our results revealed that Polybia-CP exerts its cytotoxic efficacy by disrupting the integrity of cell membrane. Furthermore, molecular dynamics (MD) simulations were employed to investigate the mechanism of membrane perturbation. Both the MD simulations and the experimental data indicated that Polybia-CP takes a standard α-helix conformation in the membrane. These findings together with the other experimental results support a speculation of mechanism similar to the “carpet” model.

  • novel mode of action of Polybia mpi a novel antimicrobial peptide in multi drug resistant leukemic cells
    Cancer Letters, 2009
    Co-Authors: Kairong Wang, Bangzhi Zhang, Rui Wang, Jiexi Yan, Jingjing Song, Pengfei Jia
    Abstract:

    As the frequent emergency of resistant tumor cells during treatment, the development of new agents with new modes of action attracts a great deal of interest. Polybia-MPI was a short cationic α-helical amphiphilic peptide that has selective toxicity toward cancer cells but no hemolytic activity. Its target selectivity is based on the binding preference to membranes containing anionic phospholipids by electrostatic driving. Its ability to make PI and trypan blue permeate into tumor cells at the same rate (within minutes), suggests a killing mechanism that involves plasma membrane perturbation. SEM and confocal microscopy experiments verified that the cell died as a result of acute injury and bursting, suggesting necrosis. As compared to the conventional chemotherapy, Polybia-MPI targets at the cell membrane rather than enters into the cell to exert its action. So it is difficult for tumor cells to develop resistance to Polybia-MPI during treatment and its action is not affected by the common multi-drug resistant mechanism. Although this is an initial study that looked at its in vitro activity rather than the in vivo activity, with the increasing resistance of conventional chemotherapy, Polybia-MPI may offer a novel therapeutic strategy in the treatment of multi-drug resistant cancer.

Kairong Wang - One of the best experts on this subject based on the ideXlab platform.

  • tryptic stability and antimicrobial activity of the derivatives of Polybia cp with fine tuning modification in the side chain of lysine
    International Journal of Peptide Research and Therapeutics, 2021
    Co-Authors: Fengjing Jia, Wenjin Yan, Jiayi Wang, Xiaolei Liang, Lishi Zhang, Jingjing Zhou, Fangfang Zhang, Kairong Wang
    Abstract:

    Antimicrobial peptides (AMPs) were believed to be a class of promising antimicrobials to combat the increasing resistant microbes. However, AMPs could be easily degraded by endogenous proteases, which limited their clinic use. Considering that lysine is the only one cationic amino acid residue in Polybia-CP which were related to the cleavage of trypsin like serine protease’s digestion, we introduced lysine’s mimics which kept the key function group side chain –NH2 and only varied the methylene chains in the sequence of Polybia-CP to investigate the effect of the introduction of non-proteinogenic amino acids on the activity and stability of antimicrobial peptides. In addition, two analogs in which lysine were substituted by the other two proteinogenic cationic amino acids arginine and histidine also were synthesized to evaluate the effect of fine tuning the function group in lysine on its antimicrobial activity and stability. We found that the introduction of amino acids with shortened side chain length of lysine could enhance the trypsin resistance of the derivatives of Polybia-CP, while maintain the same or comparable antimicrobial activity with the parent peptide. In addition, while lysine was substituted by histidine, His-CP demonstrated comparable antimicrobial activity and dramatically improved trypsin resistance. Although the analog exhibited excellent antimicrobial activity while lysine was substituted by Arginine residue (Arg-CP), its enzymatic stability was almost the same as its parent peptide. These results suggest that the fine-tuning of side chain of lysine may offer a promising strategy to improve the tryptic stability and retain the antimicrobial activity of antimicrobial peptide.

  • antimicrobial activity and stability of the d amino acid substituted derivatives of antimicrobial peptide Polybia mpi
    AMB Express, 2016
    Co-Authors: Yanyan Zhao, Kairong Wang, Ranran Zhu, Shuai Qiu, Min Zhang, Jiayi Wang, Jinxiu Peng, Ping Zhao, Hailin Wang, Wenjin Yan
    Abstract:

    Antimicrobial peptide has the potential to be developed as new kind of antimicrobial agents with novel action mechanism. However, the susceptibility to protease is a drawback for potential peptides to be clinical used. d-amino acid substitution can be one way to increase the proteolytic stability of peptides. In the present study, we synthesized the d-lysines substituted analog (d-lys-MPI) and the d-enantiomer of Polybia-MPI (D-MPI) to improve the proteolytic resistance of Polybia-MPI. Our results showed that, the stability of its d-amino acid partially substituted analog d-lys-MPI was increased. However, it lost antimicrobial activity at the tested concentration with the loss of α-helix content. As shown in the CD spectra, after substitution, the spectra of D-MPI is symmetrical to MPI, indicated it turned into left hand α-helical conformation. Excitingly, the stability of D-MPI toward the tested protease was improved greatly. Notably, the antimicrobial activity of D-MPI was comparable to its L-counterpart MPI, even improved. In addition, the hemolytic activity of D-MPI was lowered. This also indicated that the action target of antimicrobial peptide Polybia-MPI was not chiral specific. So, D-MPI may offer a therapeutic strategy to defend the infection of microbes, considering its stability to protease and relatively lower cytotoxicity to human erythrocytes.

  • Membrane-Active Action Mode of Polybia-CP, a Novel Antimicrobial Peptide Isolated from the Venom of Polybia paulista
    2016
    Co-Authors: Kairong Wang, Wen Dang, Bangzhi Zhang, Jiexi Yan, Ru Chen, Wei Zhang, Jingjing Song, Rui Wang
    Abstract:

    The extensive use of antibiotics in medicine, the food industry, and agriculture has resulted in the frequent emergence of multi-drug-resistant bacteria, which creates an urgent need for new antibiotics. It is now widely recognized that antimicrobial peptides (AMPs) could play a promising role in fighting multidrug-resistant bacteria. Antimicrobial peptide Polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized Polybia-CP and studied its action mode of anti-bacterial activity. Our results revealed that Polybia-CP has potent antibacterial activity against both Gram-positive and Gram-negative bacteria. The results from both the real bacterial membrane and the in vitromodel membrane showed that Polybia-CP is membrane active and that its action target is the membrane of bacteria. It is difficult for bacteria to develop resistance to poly-bia-CP, which may thus offer a new strategy for defending against resistant bacteria in medicine and the food and farming industries. InMay 2011, an increased number of cases of enterohemorrhagicEscherichia coli (EHEC) infections with severe disease courses and fatalities occurred in Europe, which were caused by EHEC-contaminated food (e.g., vegetables, fruits, or meat). This event caused panic all over the world, for the isolated EHEC is resistant to antibiotics and caused severe economic losses in the agriculture industry. As we know, E. coli, one of the bacillus species, is widel

  • antifungal effect and action mechanism of antimicrobial peptide Polybia cp
    Journal of Peptide Science, 2016
    Co-Authors: Kairong Wang, Wen Dang, Yanyan Zhao, Fengjing Jia, Ranran Zhu, Mengyang Sun, Shuai Qiu, Yuanyuan Zhu, Jiexi Yan, Ziqing Kong
    Abstract:

    The incidence of life-threatening invasive fungal infections increased significantly in recent years. However, the antifungal therapeutic options are very limited. Antimicrobial peptides are a class of potential lead chemical for the development of novel antifungal agents. Antimicrobial peptide Polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized Polybia-CP and determined its antifungal effects against a series of Candidian species. Our results showed that Polybia-CP has potent antifungal activity and fungicidal activity against the tested fungal cells with a proposed membrane-active action mode. In addition, Polybia-CP could induce the increase of cellular reactive oxygen species production, which would attribute to its antifungal activity. In conclusion, the present study suggests that Polybia-CP has potential as an antifungal agent or may offer a new strategy for antifungal therapeutic option.

  • dual antifungal properties of cationic antimicrobial peptides Polybia mpi membrane integrity disruption and inhibition of biofilm formation
    Peptides, 2014
    Co-Authors: Kairong Wang, Wen Dang, Bangzhi Zhang, Yanyan Zhao, Wei Chen, Rui Wang
    Abstract:

    Abstract With the increasing emergence of resistant fungi, the discovery and development of novel antifungal therapeutics were urgently needed. Compared with conventional antibiotics, the limited propensity of AMPs to induce resistance in pathogens has attracted great interest. In the present study, the antifungal activity and its mechanism-of-action of Polybia-MPI, a cationic peptide from the venom of Social wasp Polybia Paulista was investigated. We demonstrated that Polybia-MPI could potently inhibit the growth of Candida albicans (C. albicans) and Candida glabrata (C. glabrata). The 50% inhibitory concentrations (IC50) of Polybia-MPI against cancer cells were much higher than the MICs against the tested C. albicans and C. glabrata cells, indicating that Polybia-MPI had high selectivity between the fungal and mammalian cells. Our results also indicated that membrane disturbance mechanism was involved in the antifungal activity. Furthermore, Polybia-MPI could inhibit the bio film forming of C. glabrata, which was frequently associated with clinically significant biofilm. These results suggest that Polybia-MPI has great advantages in the development of antifungal agents.

Herbert Hildebrandt - One of the best experts on this subject based on the ideXlab platform.

  • polysialic acid modification of the synaptic cell adhesion molecule syncam 1 in human embryonic stem cell derived oligodendrocyte precursor cells
    Stem Cell Research, 2015
    Co-Authors: Sebastian Werneburg, Martina Mühlenhoff, Falk F R Buettner, Herbert Hildebrandt
    Abstract:

    Oligodendrocyte precursor cells (OPCs) are the progenitors of myelinating oligodendrocytes in brain development and repair. Successful myelination depends on the control of adhesiveness during OPC migration and axon contact formation. The decoration of cell surface proteins with the glycan polysialic acid (polySia) is a key regulatory element of OPC interactions during development and under pathological conditions. By far the major protein carrier of polySia is the neural cell adhesion molecule NCAM, but recently, polysialylation of the synaptic cell adhesion molecule SynCAM 1 has been detected in the developing mouse brain. In mice, polySia-SynCAM 1 is associated with cells expressing NG2, a marker of a heterogeneous precursor cell population, which is the primary source for oligodendrocytes in development and myelin repair but can also give rise to astrocytes and possibly neurons. It is not yet clear if polySia-SynCAM 1 is expressed by OPCs and its occurrence in humans is elusive. By generating uniform human embryonic stem cell-derived OPC cultures, we demonstrate that polySia is present on human OPCs but down-regulated during differentiation into myelin basic protein-positive oligodendrocytes. PolySia on NCAM resides on the isoforms NCAM-180 and NCAM-140, and SynCAM 1 is identified as a novel polySia acceptor in human OPCs.

  • synaptic cell adhesion molecule syncam 1 is a target for polysialylation in postnatal mouse brain
    Proceedings of the National Academy of Sciences of the United States of America, 2010
    Co-Authors: Sebastian P. Galuska, Herbert Hildebrandt, Birgit Weinhold, Manuela Rollenhagen, Imke Oltmannnorden, Moritz Kaup, Katinka Eggers, Miriam Schiff, Maike Hartmann, Rudolf Geyer
    Abstract:

    Among the large set of cell surface glycan structures, the carbohydrate polymer polysialic acid (polySia) plays an important role in vertebrate brain development and synaptic plasticity. The main carrier of polySia in the nervous system is the neural cell adhesion molecule NCAM. As polySia with chain lengths of more than 40 sialic acid residues was still observed in brain of newborn Ncam−/− mice, we performed a glycoproteomics approach to identify the underlying protein scaffolds. Affinity purification of polysialylated molecules from Ncam−/− brain followed by peptide mass fingerprinting led to the identification of the synaptic cell adhesion molecule SynCAM 1 as a so far unknown polySia carrier. SynCAM 1 belongs to the Ig superfamily and is a powerful inducer of synapse formation. Importantly, the appearance of polysialylated SynCAM 1 was not restricted to the Ncam−/− background but was found to the same extent in perinatal brain of WT mice. PolySia was located on N-glycans of the first Ig domain, which is known to be involved in homo- and heterophilic SynCAM 1 interactions. Both polysialyltransferases, ST8SiaII and ST8SiaIV, were able to polysialylate SynCAM 1 in vitro, and polysialylation of SynCAM 1 completely abolished homophilic binding. Analysis of serial sections of perinatal Ncam−/− brain revealed that polySia-SynCAM 1 is expressed exclusively by NG2 cells, a multifunctional glia population that can receive glutamatergic input via unique neuron-NG2 cell synapses. Our findings sug-gest that polySia may act as a dynamic modulator of SynCAM 1 functions during integration of NG2 cells into neural networks.

  • genesis of rods in the zebrafish retina occurs in a microenvironment provided by polysialic acid expressing muller glia
    The Journal of Comparative Neurology, 2010
    Co-Authors: S Kustermann, Herbert Hildebrandt, Sylvia Bolz, Katja Dengler, Konrad Kohler
    Abstract:

    Polysialic acid (polySia) is a posttranslational modification of the neural cell adhesion molecule NCAM, which in the vertebrate brain is dynamically regulated during development and crucially involved in developmental and adult neurogenesis. In the fish retina, new neurons are persistently generated, but the possible contribution of polySia has not yet been addressed. Here we used immunohistochemistry with NCAM- and polySia-specific antibodies to study spatiotemporal expression patterns of NCAM and polySia in the developing and mature zebrafish retina. As early as 2.3 days postfertilization (dpf), NCAM but not polySia was detected on cell somata and fibers of the developing retina. At 4.3 dpf polySia immunoreactivity first appeared in the ventral retina and was localized to the nascent outer nuclear layer (ONL). In mature zebrafish, polySia immunoreactivity in the ONL extended to the entire retina. Colocalization with rhodopsin-EGFP in transgenic zebrafish or the Muller glia-specific protein cellular retinaldehyde-binding protein (CRALBP) revealed that polySia immunoreactivity was confined to the compartment of radial Muller glia processes crossing the ONL and to a small band of processes positioned proximal to the horizontal cell layer of the mature retina. As shown by 5-bromo-2-deoxyuridine (BrdU) labeling, both newly generated rod precursors within the mature ONL and precursors of the marginal zone were polySia-negative. Thus, polySia-negative rod precursors of the mature zebrafish retina face a polySia-NCAM-positive microenvironment presented by radial Muller glia. In view of the prominent role of polySia in other neurogenic systems, this pattern indicates that polySia provides environmental cues that are relevant for the generation of new rods. J. Comp. Neurol. 518:636–646, 2010. © 2009 Wiley-Liss, Inc.

  • impact of the polysialyltransferases st8siaii and st8siaiv on polysialic acid synthesis during postnatal mouse brain development
    Journal of Biological Chemistry, 2008
    Co-Authors: Imke Oltmannnorden, Herbert Hildebrandt, Rita Gerardyschahn, Sebastian P. Galuska, Rudolf Geyer, Hildegard Geyer, Martina Mühlenhoff
    Abstract:

    Abstract Polysialic acid (polySia), a post-translational modification of the neural cell adhesion molecule (NCAM), is the key regulator of NCAM-mediated functions and crucial for normal brain development, postnatal growth, and survival. Two polysialyltransferases, ST8SiaII and ST8SiaIV, mediate polySia biosynthesis. To dissect the impact of each enzyme during postnatal brain development, we monitored the developmental changes in NCAM polysialylation in wild-type, ST8SiaII-, and ST8SiaIV-deficient mice using whole brain lysates obtained at 10 time points from postnatal days 1 to 21 and from adult mice. In wild-type and ST8SiaIV-null brain, polySia biosynthesis kept pace with the rapid increase in brain weight until day 9, and nearly all NCAM was polysialylated. Thereafter, polySia dropped by ∼70% within 1 week, accompanied by the first occurrence of polySia-free NCAM-140 and NCAM-180. In ST8SiaII-null brain, polySia declined immediately after birth, leading to 60% less polySia at day 9 combined with the untimely appearance of polySia-free NCAM. Polysialyltransferase deficiency did not alter NCAM expression level or isoform pattern. In all three genotypes, NCAM-140 and NCAM-180 were expressed at constant levels from days 1 to 21 and provided the major polySia acceptors. By contrast, NCAM-120 first appeared at day 5, followed by a strong up-regulation inverse to the decrease in polySia. Together, we provide a comprehensive quantitative analysis of the developmental changes in polySia level, NCAM polysialylation status, and polysialyltransferase transcript levels and show that the predominant role of ST8SiaII during postnatal brain development is restricted to the first 15 days.

  • dissecting polysialic acid and ncam functions in brain development
    Journal of Neurochemistry, 2007
    Co-Authors: Herbert Hildebrandt, Martina Mühlenhoff, Birgit Weinhold, Rita Gerardyschahn
    Abstract:

    The unique modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is tightly associated with nervous system development and plasticity. The prevailing view that this large carbohydrate polymer acts as an anti-adhesive factor seems straightforward at first sight. However, during almost 25 years of polySia research it became increasingly clear that the impact of polySia on cell surface interactions can not be explained by one unifying mechanism. Recent progress in the generation of mouse models, which partially or completely lack polySia due to ablation of one or both of the two polySia synthesizing enzymes, provides novel insights into the function of this unique post-translational modification. The present review is focused on a phenotype comparison between the newly established mouse strains which combine polySia-deficiency with normal NCAM expression and the well-characterized NCAM negative mouse model. Analysis of shared and individual phenotypes allows a clear distinction between NCAM and polySia functions and revealed that polySia plays a vital role as a specific control element of NCAM-mediated interactions.

Bangzhi Zhang - One of the best experts on this subject based on the ideXlab platform.

  • Membrane-Active Action Mode of Polybia-CP, a Novel Antimicrobial Peptide Isolated from the Venom of Polybia paulista
    2016
    Co-Authors: Kairong Wang, Wen Dang, Bangzhi Zhang, Jiexi Yan, Ru Chen, Wei Zhang, Jingjing Song, Rui Wang
    Abstract:

    The extensive use of antibiotics in medicine, the food industry, and agriculture has resulted in the frequent emergence of multi-drug-resistant bacteria, which creates an urgent need for new antibiotics. It is now widely recognized that antimicrobial peptides (AMPs) could play a promising role in fighting multidrug-resistant bacteria. Antimicrobial peptide Polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized Polybia-CP and studied its action mode of anti-bacterial activity. Our results revealed that Polybia-CP has potent antibacterial activity against both Gram-positive and Gram-negative bacteria. The results from both the real bacterial membrane and the in vitromodel membrane showed that Polybia-CP is membrane active and that its action target is the membrane of bacteria. It is difficult for bacteria to develop resistance to poly-bia-CP, which may thus offer a new strategy for defending against resistant bacteria in medicine and the food and farming industries. InMay 2011, an increased number of cases of enterohemorrhagicEscherichia coli (EHEC) infections with severe disease courses and fatalities occurred in Europe, which were caused by EHEC-contaminated food (e.g., vegetables, fruits, or meat). This event caused panic all over the world, for the isolated EHEC is resistant to antibiotics and caused severe economic losses in the agriculture industry. As we know, E. coli, one of the bacillus species, is widel

  • dual antifungal properties of cationic antimicrobial peptides Polybia mpi membrane integrity disruption and inhibition of biofilm formation
    Peptides, 2014
    Co-Authors: Kairong Wang, Wen Dang, Bangzhi Zhang, Yanyan Zhao, Wei Chen, Rui Wang
    Abstract:

    Abstract With the increasing emergence of resistant fungi, the discovery and development of novel antifungal therapeutics were urgently needed. Compared with conventional antibiotics, the limited propensity of AMPs to induce resistance in pathogens has attracted great interest. In the present study, the antifungal activity and its mechanism-of-action of Polybia-MPI, a cationic peptide from the venom of Social wasp Polybia Paulista was investigated. We demonstrated that Polybia-MPI could potently inhibit the growth of Candida albicans (C. albicans) and Candida glabrata (C. glabrata). The 50% inhibitory concentrations (IC50) of Polybia-MPI against cancer cells were much higher than the MICs against the tested C. albicans and C. glabrata cells, indicating that Polybia-MPI had high selectivity between the fungal and mammalian cells. Our results also indicated that membrane disturbance mechanism was involved in the antifungal activity. Furthermore, Polybia-MPI could inhibit the bio film forming of C. glabrata, which was frequently associated with clinically significant biofilm. These results suggest that Polybia-MPI has great advantages in the development of antifungal agents.

  • membrane active antimicrobial activity and molecular dynamics study of a novel cationic antimicrobial peptide Polybia mpi from the venom of Polybia paulista
    Peptides, 2013
    Co-Authors: Kairong Wang, Wen Dang, Bangzhi Zhang, Jiexi Yan, Ru Chen, Wei Zhang, Jindao Zhang, Xin Liu, Ming Kai, Wenjin Yan
    Abstract:

    As the frequent emergence of the resistant bacteria, the development of new agents with a new action mode attracts a great deal of interest. It is now widely accepted that antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics. In this study, antimicrobial peptide Polybia-MPI and its analogs were synthesized and their antibacterial activity was studied. Our results revealed that Polybia-MPI has potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Its ability to make PI permeate into bacteria and lead to the leakage of calcein from model membrane LUVs, suggests a killing mechanism involving membrane perturbation. SEM and TEM microscopy experiments verified that the morphology of bacteria was changed greatly under the treatment of Polybia-MPI. Compared with the conventional chemotherapy, Polybia-MPI targets the cell membrane rather than entering into the cell to exert its antibacterial activity. Furthermore, molecular dynamics (MD) simulations were employed to investigate the mechanism of membrane perturbation. The results indicated that the α-helical conformation in the membrane is required for the exhibition of antibacterial activity and the membrane disturbance by Polybia-MPI is a cooperative process. In conclusion, with the increasing resistance to conventional antibiotics, there is no doubt that Polybia-MPI could offer a new strategy to defend the resistant bacteria.

  • membrane active action mode of Polybia cp a novel antimicrobial peptide isolated from the venom of Polybia paulista
    Antimicrobial Agents and Chemotherapy, 2012
    Co-Authors: Kairong Wang, Wen Dang, Bangzhi Zhang, Jiexi Yan, Ru Chen, Wei Zhang, Jingjing Song, Rui Wang
    Abstract:

    The extensive use of antibiotics in medicine, the food industry, and agriculture has resulted in the frequent emergence of multidrug-resistant bacteria, which creates an urgent need for new antibiotics. It is now widely recognized that antimicrobial peptides (AMPs) could play a promising role in fighting multidrug-resistant bacteria. Antimicrobial peptide Polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized Polybia-CP and studied its action mode of antibacterial activity. Our results revealed that Polybia-CP has potent antibacterial activity against both Gram-positive and Gram-negative bacteria. The results from both the real bacterial membrane and the in vitro model membrane showed that Polybia-CP is membrane active and that its action target is the membrane of bacteria. It is difficult for bacteria to develop resistance to Polybia-CP, which may thus offer a new strategy for defending against resistant bacteria in medicine and the food and farming industries.

  • novel cytotoxity exhibition mode of Polybia cp a novel antimicrobial peptide from the venom of the social wasp Polybia paulista
    Toxicology, 2011
    Co-Authors: Kairong Wang, Wen Dang, Bangzhi Zhang, Rui Wang, Ru Chen, Wei Zhang, Jingjing Song, Jindao Zhang
    Abstract:

    Abstract Antimicrobial peptide Polybia-CP was purified from the venom of the social wasp Polybia paulista. It has an amphipathic sequence ILGTILGLLKSL-NH2 and possesses potent antimicrobial activity against both Gram-positive and Gram-negative bacteria. In this study we synthesized Polybia-CP, studied its cytotoxity on tumor cells and proposed its possible mechanism. Our results revealed that Polybia-CP exerts its cytotoxic efficacy by disrupting the integrity of cell membrane. Furthermore, molecular dynamics (MD) simulations were employed to investigate the mechanism of membrane perturbation. Both the MD simulations and the experimental data indicated that Polybia-CP takes a standard α-helix conformation in the membrane. These findings together with the other experimental results support a speculation of mechanism similar to the “carpet” model.

Mario Sergio Palma - One of the best experts on this subject based on the ideXlab platform.

  • Hyperalgesic and edematogenic effects of peptides isolated from the venoms of honeybee (Apis mellifera) and neotropical social wasps (Polybia paulista and Protonectarina sylveirae)
    Amino Acids, 2011
    Co-Authors: P. Brigatte, Y. Cury, B. M. Souza, N. B. Baptista-saidemberg, D. M. Saidemberg, V. P. Gutierrez, Mario Sergio Palma
    Abstract:

    Stings by bees and wasps, including Brazilian species, are a severe public health problem. The local reactions observed after the envenoming includes typical inflammatory response and pain. Several studies have been performed to identify the substances, including peptides that are responsible for such phenomena. The aim of the present study is to characterize the possible nociceptive (hyperalgesic) and edematogenic effects of some peptides isolated from the venoms of the honeybee ( Apis mellifera ) and the social wasps Polybia paulista and Protonectarina sylveirae , in addition to characterize some of the mechanisms involved in these phenomena. For this purpose, different doses of the peptides mellitin ( Apis mellifera ), Polybia-MP-I, N-2-Polybia-MP-I ( Polybia paulista ), Protonectarina-MP-NH2 and Protonectarina-MP-OH ( Protonectarina sylveirae) were injected into the hind paw of mice. Hyperalgesia and edema were determined after peptide application, by using an electronic von Frey apparatus and a paquimeter. Carrageenin and saline were used as controls. Results showed that melittin, Polybia-MP-I, N-2-Polybia-MP-I, Protonectarina-MP-NH_2 and Protonectarina-MP-OH peptides produced a dose- and time-related hyperalgesic and edematogenic responses. Both phenomena are detected 2 h after melittin, Polybia-MP-I, N-2-Polybia-MP-I injection; their effects lasted until 8 h. In order to evaluate the role of prostanoids and the involvement of lipidic mediators in hyperalgesia induced by the peptides, indomethacin and zileuton were used. Results showed that zileuton blocked peptide-induced hyperalgesia and induced a decrease of the edematogenic response. On the other hand, indomethacin did not interfere with these phenomena. These results indicate that melittin, Polybia-MP-I, N-2-Polybia-MP-I, Protonectarina-MP-NH_2, and Protonectarina-MP-OH peptides could contribute to inflammation and pain induced by insect venoms.

  • Inflammation and apoptosis induced by mastoparan Polybia-MPII on skeletal muscle
    Toxicon : official journal of the International Society on Toxinology, 2010
    Co-Authors: Thalita Rocha, Bibiana Monson De Souza, Mario Sergio Palma, Luciano Libardi Soares De Barros, Karina Fontana, Maria Alice Cruz-höfling
    Abstract:

    Mastoparan firstly described as an inducer of mast cell granules exocytosis has been also related to many essential mechanisms of cell function. In skeletal muscle tissue the best characterization of mastoparan effect was induction of myonecrosis. We examined the ability of mastoparan Polybia-MPII from Polybia paulista wasp venom to induce apoptosis and inflammation in mouse tibial anterior muscle. The activation of caspase 3 and 9, the expression of TNF-alpha, IFN-gamma, CD68 and CD163 proteins, specific of resident and migrant macrophages, respectively, were examined (3h to 21d). TUNEL-positive nuclei were found both in damaged and normal-looking muscle fibres, whereas the caspases, cytokines and macrophages proteins were only in damaged fibres. The caspase 3 and 9 expression and the immunolabelled areas of TNF-alpha and IFN-gamma were significantly higher compared to control. TUNEL-positive nuclei and TNF-alpha expression were also present in regenerating fibres. CD68 and CD163 signalize necrotic debris removal, release of chemo-attractants and cytokines which have been considered a pre-requisite for muscle regeneration. High levels of cytokines coincided with the intense muscle proteolysis by mastoparan (3-24h) and the climax of regeneration (3 d) whereas cytokines decline corresponded to periods of tissue remodeling and intense fibre protein synthesis (7-21 d). We conclude that the mastoparan Polybia-MPII causes myonecrosis and apoptosis, the latter probably involving caspases signalling, corroborated by mitochondrial damage, and cytokines activation.

  • characterization of two novel polyfunctional mastoparan peptides from the venom of the social wasp Polybia paulista
    Peptides, 2009
    Co-Authors: Bibiana Monson De Souza, Marcia Perez Dos Santos Cabrera, Joao Ruggiero Neto, Alessandra Silva, Virginia Maria Ferreira Resende, Helen Andrade Arcuri, Mario Sergio Palma
    Abstract:

    Hymenoptera venoms are complex mixtures of biochemically and pharmacologically active components such as biogenic amines, peptides and proteins. Polycationic peptides generally constitute the largest group of Hymenoptera venom toxins, and the mastoparans constitute the most abundant and important class of peptides in the venom of social wasps. These toxins are responsible for histamine release from mast cells, serotonin from platelets, and catecholamines and adenylic acids from adrenal chromafin cells. The present work reports the structural and functional characterization of two novel mastoparan peptides identified from the venom of the neotropical social wasp Polybia paulista. The mastoparans Polybia-MP-II and -III were purified, sequenced and synthesized on solid phase using Fmoc chemistry and the synthetic peptides used for structural and functional characterizations. Polybia-MP-II and -III are tetradecapeptides, amidated at their C-termini, and form amphipathic α-helical conformations under membrane-mimetic conditions. Both peptides were polyfunctional, causing pronounced cell lysis of rat mast cells and erythrocytes, in addition to having antimicrobial activity against both Gram-positive and Gram-negative bacteria.

  • influence of the bilayer composition on the membrane disruption effect of Polybia mp1 a mastoparan peptide with antimicrobial and leukemic cell selectivity
    Biophysical Journal, 2009
    Co-Authors: Marcia Perez Dos Santos Cabrera, Bibiana Monson De Souza, Joao Ruggiero Neto, Mario Sergio Palma, Manoel Arcisiomiranda, Renata Gorjao, Natalia Bueno Leite, Rui Cury, Joaquim Procopio
    Abstract:

    Unlike other mastoparans, Polybia-MP1 (IDWKKLLDAAKQIL), from the venom Polybia paulista (wasp), is highly selective for bacterial cells. By flow cytometry, we also found out this selective behavior: Polybia-MP1 promoted a decrease of 60 % cell viability at 25 μM in Jurkat (leukemic) cells, while it was not altered in primary human lymphocytes. The mechanism of selectivity was studied in the interaction with different bilayers. Ion channel-like activity was detected at 0.12 μM peptide concentration with anionic lipid membranes of azolectin, showing conductance in the range of 250 pS. On zwitterionic diphytanoylphosphatidylcholine-(DPhPC) it required 0.18 μM for the same conductance level. Further experiments with DPhPC bilayers containing 30% phophatidylserine or cardiolipin required higher peptide concentration to induce single channel events at slightly lower conductance levels. However, the presence of 20 mol% cholesterol in the mixture significantly reduced the ion channel-like activity, dropped the average conductance to around 120 pS and required 0.30 μM. On vesicles the activity of Polybia-MP1 also shows greater rate of leakage on the anionic over the zwitterionic, impaired by the presence of cholesterol; the lytic activity is characterized by a threshold peptide to lipid molar ratio that depends on the phospholipid composition. Preliminary results of changes in DPH anisotropy and acrylamide quenching of Trp fluorescence show a slight decrease in the anisotropy, and a significant quenching of the Trp fluorescence, indicating small influence on the lipid packing associated to preferential interaction with the lipid head group region. Results suggest that the selectivity of Polybia-MP1 is a consequence of a shallow interaction with zwitterionic bilayers, favored by the presence and position of negatively charged Asp residues, which is not possible for other mastoparan peptides.Support: CAPES, CNPq, FAPESP

  • selectivity in the mechanism of action of antimicrobial mastoparan peptide Polybia mp1
    European Biophysics Journal, 2008
    Co-Authors: Bibiana Monson De Souza, Marcia Perez Dos Santos Cabrera, Mario Sergio Palma, Sabrina Thais Broggio Costa, Jose Roberto Ruggiero, Joao Ruggiero Neto
    Abstract:

    Many potent antimicrobial peptides also present hemolytic activity, an undesired collateral effect for the therapeutic application. Unlike other mastoparan peptides, Polybia-MP1 (IDWKKLLDAAKQIL), obtained from the venom of the social wasp Polybia paulista, is highly selective of bacterial cells. The study of its mechanism of action demonstrated that it permeates vesicles at a greater rate of leakage on the anionic over the zwitterionic, impaired by the presence of cholesterol or cardiolipin; its lytic activity is characterized by a threshold peptide to lipid molar ratio that depends on the phospholipid composition of the vesicles. At these particular threshold concentrations, the apparent average pore number is distinctive between anionic and zwitterionic vesicles, suggesting that pores are similarly formed depending on the ionic character of the bilayer. To prospect the molecular reasons for the strengthened selectivity in Polybia-MP1 and its absence in Mastoparan-X, MD simulations were carried out. Both peptides presented amphipathic α-helical structures, as previously observed in Circular Dichroism spectra, with important differences in the extension and stability of the helix; their backbone solvation analysis also indicate a different profile, suggesting that the selectivity of Polybia-MP1 is a consequence of the distribution of the charged and polar residues along the peptide helix, and on how the solvent molecules orient themselves according to these electrostatic interactions. We suggest that the lack of hemolytic activity of Polybia-MP1 is due to the presence and position of Asp residues that enable the equilibrium of electrostatic interactions and favor the preference for the more hydrophilic environment.