scholarly journals Interaction of the Gelsolin-Derived Antibacterial PBP 10 Peptide with Lipid Bilayers and Cell Membranes

2006 ◽  
Vol 50 (9) ◽  
pp. 2932-2940 ◽  
Author(s):  
Robert Bucki ◽  
Paul A. Janmey
Keyword(s):  
Antimicrobial Peptides ◽  
Lipid Bilayers ◽  
Cell Membranes ◽  
Plasma Membranes ◽  
Antimicrobial Activities ◽  
Eukaryotic Cells ◽  
Hypotonic Solution ◽  
Antibacterial Peptides ◽  
Bacterial Killing ◽  
Bacterial Membranes

ABSTRACTPBP 10, an antibacterial, cell membrane-permeant rhodamine B-conjugated peptide derived from the polyphosphoinositide binding site of gelsolin, interacts selectively with both lipopolysaccharides (LPS) and lipoteichoic acid (LTA), the distinct components of gram-negative and gram-positive bacteria, respectively. Isolated LPS and LTA decrease the antimicrobial activities of PBP 10, as well as other antimicrobial peptides, such as cathelicidin-LL37 (LL37) and mellitin. In an effort to elucidate the mechanism of bacterial killing by PBP 10, we compared its effects on artificial lipid bilayers and eukaryotic cell membranes with the actions of the mellitin, magainin II, and LL37 peptides. This study reveals that pore formation is unlikely to be involved in PBP 10-mediated membrane destabilization. We also investigated the effects of these peptides on platelets and red blood cells (RBCs). Comparison of these antimicrobial peptides shows that only mellitin has a toxic effect on platelets and RBCs in a concentration range concomitant with its bactericidal activity. The hemolytic activities of the PBP 10 and LL37 peptides significantly increase when RBCs are osmotically swollen in hypotonic solution, indicating that these antibacterial peptides may take advantage of the more extended form of bacterial membranes in exerting their killing activities. Additionally, we found that LL37 hemolytic activity was much higher when RBCs were induced to expose phosphatidylserine to the external leaflet of their plasma membranes. This finding suggests that asymmetrical distribution of phospholipids in the external membranes of eukaryotic cells may represent an important factor in determining the specificity of antibacterial peptides for targeting bacteria rather than eukaryotic cells.

scholarly journals Detection of selective antibacterial peptides by the Polarity Profile method.

2013 ◽  
Vol 60 (2) ◽  
Author(s):  
Carlos Polanco ◽  
Thomas Buhse ◽  
José Lino Samaniego ◽  
Jorge Alberto Castañón-González
Keyword(s):  
Antimicrobial Peptides ◽  
Mammalian Cells ◽  
False Negative ◽  
Antibacterial Peptides ◽  
Index Method ◽  
Profile Method ◽  
Bacterial Membranes ◽  
Polarity Index ◽  
Polarity Profile ◽  
Almost All

Antimicrobial peptides occupy a prominent place in the production of pharmaceuticals, because of their effective contribution to the protection of the immune system against almost all types of pathogens. These peptides are thoroughly studied by computational methods designed to shed light on their main functions. In this paper, we propose a computational approach, named the Polarity Profile method that represents an improvement to the former Polarity Index method. The Polarity Profile method is very effective in detecting the subgroup of antibacterial peptides called selective cationic amphipathic antibacterial peptides (SCAAP) that show high toxicity towards bacterial membranes and exhibit almost zero toxicity towards mammalian cells. Our study was restricted to the peptides listed in the antimicrobial peptides database (APD2) of December 19, 2012. Performance of the Polarity Profile method is demonstrated through a comparison to the former Polarity Index method by using the same sets of peptides. The efficiency of the Polarity Profile method exceeds 85% taking into account the false positive and/or false negative peptides.

scholarly journals Antimicrobial Activities and Structures of Two Linear Cationic Peptide Families with Various Amphipathic β-Sheet and α-Helical Potentials

2005 ◽  
Vol 49 (12) ◽  
pp. 4957-4964 ◽  
Author(s):  
Yi Jin ◽  
Janet Hammer ◽  
Michelle Pate ◽  
Yu Zhang ◽  
Fang Zhu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Plasma Membranes ◽  
Membrane Lipids ◽  
Lipid Vesicles ◽  
Selective Advantage ◽  
Antimicrobial Activities ◽  
Helical Conformation ◽  
Bacterial Cells ◽  
Β Sheet

ABSTRACT Many naturally occurring antimicrobial peptides comprise cationic linear sequences with the potential to adopt an amphipathic α-helical conformation. We designed a linear 18-residue peptide that adopted an amphipathic β-sheet structure when it was bound to lipids. In comparison to a 21-residue amphipathic α-helical peptide of equal charge and hydrophobicity, this peptide possessed more similar antimicrobial activity and greater selectivity in binding to and inducing leakage in vesicles composed of bacterial membrane lipids than vesicles composed of mammalian membrane lipids (J. Blazyk, R. Weigand, J. Klein, J. Hammer, R. M. Epand, R. F. Epand, W. L. Maloy, and U. P. Kari, J. Biol. Chem. 276:27899-27906, 2001). Here, we compare two systematically designed families of linear cationic peptides to evaluate the importance of amphipathicity for determination of antimicrobial activity. Each peptide contains six lysine residues and is amidated at the carboxyl terminus. The first family consists of five peptides with various capacities to form amphipathic β-sheet structures. The second family consists of six peptides with various potentials to form amphipathic α helices. Only those peptides that can form a highly amphipathic structure (either a β sheet or an α helix) possessed significant antimicrobial activities. Striking differences in the abilities to bind to and induce leakage in membranes and lipid vesicles were observed for the two families. Overall, the amphipathic β-sheet peptides are less lytic than their amphipathic α-helical counterparts, particularly toward membranes containing phosphatidylcholine, a lipid commonly found in mammalian plasma membranes. Thus, it appears that antimicrobial peptides that can form an amphipathic β-sheet conformation may offer a selective advantage in targeting bacterial cells.

scholarly journals Yersinia pestis lipopolysaccharide remodeling confers resistance to a Xenopsylla cheopis cecropin

2021 ◽  
Author(s):  
Basil Mathew ◽  
Kari L. Aoyagi ◽  
Mark A. Fisher
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Bacterial Infections ◽  
Antimicrobial Activities ◽  
Innate Immune Responses ◽  
Binding Assays ◽  
Bacterial Killing ◽  
Bacterial Membranes ◽  
Xenopsylla Cheopis ◽  
In The Wild

Fleas are major vectors of Yersinia pestis, the causative agent of plague. It has been proposed that Y. pestis has developed the ability to overcome the innate immune responses of fleas. Despite the fact that they transmit a number of bacterial infections, very little is known about the immune responses in fleas. In this study, we describe the antimicrobial activities of cecropin from Xenopsylla cheopis (cheopin), a major vector for Y. pestis in the wild. This is the first cecropin-class antimicrobial peptide described from Siphonaptera insects. Cheopin showed potent activity against Gram-negative bacteria, but little activity against wild-type Y. pestis KIM6+. Deletion of the aminoarabinose operon, which is responsible for the 4-amino-4-deoxy-L-arabinose (Ara4N) modification of LPS, rendered Y. pestis highly susceptible to cheopin. Confocal microscopy and whole cell binding assays indicated that Ara4N modification reduces the affinity of cheopin for Y. pestis. Further, cheopin only permeabilized bacterial membranes in the absence of Ara4N-modified LPS, which was correlated with bacterial killing. This study provides insights into innate immunity of the flea and evidence for the crucial role of Ara4N modification of Y. pestis LPS in conferring resistance against flea antimicrobial peptides.

scholarly journals Revealing the Mechanisms of Synergistic Action of Two Magainin Antimicrobial Peptides

2020 ◽  
Vol 2 ◽  
Author(s):  
Burkhard Bechinger ◽  
Dennis Wilkens Juhl ◽  
Elise Glattard ◽  
Christopher Aisenbrey
Keyword(s):  
Antimicrobial Peptides ◽  
Cooperative Behavior ◽  
Membrane Surface ◽  
Pharmaceutical Formulations ◽  
Antimicrobial Activities ◽  
Therapeutic Window ◽  
Response Curves ◽  
Bacterial Killing ◽  
Synergistic Enhancement ◽  
Bacterial Lipid

The study of peptide-lipid and peptide-peptide interactions as well as their topology and dynamics using biophysical and structural approaches have changed our view how antimicrobial peptides work and function. It has become obvious that both the peptides and the lipids arrange in soft supramolecular arrangements which are highly dynamic and able to change and mutually adapt their conformation, membrane penetration, and detailed morphology. This can occur on a local and a global level. This review focuses on cationic amphipathic peptides of the magainin family which were studied extensively by biophysical approaches. They are found intercalated at the membrane interface where they cause membrane thinning and ultimately lysis. Interestingly, mixtures of two of those peptides namely magainin 2 and PGLa which occur naturally as a cocktail in the frog skin exhibit synergistic enhancement of antimicrobial activities when investigated together in antimicrobial assays but also in biophysical experiments with model membranes. Detailed dose-response curves, presented here for the first time, show a cooperative behavior for the individual peptides which is much increased when PGLa and magainin are added as equimolar mixture. This has important consequences for their bacterial killing activities and resistance development. In membranes that carry unsaturations both peptides align parallel to the membrane surface where they have been shown to arrange into mesophases involving the peptides and the lipids. This supramolecular structuration comes along with much-increased membrane affinities for the peptide mixture. Because this synergism is most pronounced in membranes representing the bacterial lipid composition it can potentially be used to increase the therapeutic window of pharmaceutical formulations.

scholarly journals Unveiling the Multifaceted Mechanisms of Antibacterial Activity of Buforin II and Frenatin 2.3S Peptides from Skin Micro-Organs of the Orinoco Lime Treefrog (Sphaenorhynchus lacteus)

2018 ◽  
Vol 19 (8) ◽  
pp. 2170 ◽  
Author(s):  
Carolina Muñoz-Camargo ◽  
Vivian Salazar ◽  
Laura Barrero-Guevara ◽  
Sandra Camargo ◽  
Angela Mosquera ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Lipid Bilayers ◽  
Bacterial Resistance ◽  
Interaction Mechanism ◽  
Antimicrobial Activities ◽  
Immune Defense ◽  
Bacterial Cells ◽  
Amphibian Skin ◽  
Resistance Response ◽  
Membrane Destabilization

Amphibian skin is a rich source of natural compounds with diverse antimicrobial and immune defense properties. Our previous studies showed that the frog skin secretions obtained by skin micro-organs from various species of Colombian anurans have antimicrobial activities against bacteria and viruses. We purified for the first time two antimicrobial peptides from the skin micro-organs of the Orinoco lime treefrog (Sphaenorhynchus lacteus) that correspond to Buforin II (BF2) and Frenatin 2.3S (F2.3S). Here, we have synthesized the two peptides and tested them against Gram-negative and Gram-positive bacteria, observing an effective bactericidal activity at micromolar concentrations. Evaluation of BF2 and F2.3S membrane destabilization activity on bacterial cell cultures and synthetic lipid bilayers reveals a distinct membrane interaction mechanism. BF2 agglutinates E. coli cells and synthetic vesicles, whereas F2.3S shows a high depolarization and membrane destabilization activities. Interestingly, we found that F2.3S is able to internalize within bacterial cells and can bind nucleic acids, as previously reported for BF2. Moreover, bacterial exposure to both peptides alters the expression profile of genes related to stress and resistance response. Overall, these results show the multifaceted mechanism of action of both antimicrobial peptides that can provide alternative tools in the fight against bacterial resistance.

scholarly journals Regulation of Antimicrobial Peptide Activity via Tuning Deformation Fields by Membrane-Deforming Inclusions

2021 ◽  
Vol 23 (1) ◽  
pp. 326
Author(s):  
Oleg V. Kondrashov ◽  
Sergey A. Akimov
Keyword(s):  
Antimicrobial Peptides ◽  
Statistical Model ◽  
Antimicrobial Peptide ◽  
Plasma Membranes ◽  
Eukaryotic Cell ◽  
Gramicidin A ◽  
Eukaryotic Cells ◽  
Amphipathic Peptides ◽  
Transmembrane Peptides

Antimicrobial peptides (AMPs) are considered prospective antibiotics. Some AMPs fight bacteria via cooperative formation of pores in their plasma membranes. Most AMPs at their working concentrations can induce lysis of eukaryotic cells as well. Gramicidin A (gA) is a peptide, the transmembrane dimers of which form cation-selective channels in membranes. It is highly toxic for mammalians as being majorly hydrophobic gA incorporates and induces leakage of both bacterial and eukaryotic cell membranes. Both pore-forming AMPs and gA deform the membrane. Here we suggest a possible way to reduce the working concentrations of AMPs at the expense of application of highly-selective amplifiers of AMP activity in target membranes. The amplifiers should alter the deformation fields in the membrane in a way favoring the membrane-permeabilizing states. We developed the statistical model that allows describing the effect of membrane-deforming inclusions on the equilibrium between AMP monomers and cooperative membrane-permeabilizing structures. On the example of gA monomer-dimer equilibrium, the model predicts that amphipathic peptides and short transmembrane peptides playing the role of the membrane-deforming inclusions, even in low concentration can substantially increase the lifetime and average number of gA channels.

scholarly journals Plant antimicrobial peptides: structures, functions, and applications

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Junpeng Li ◽  
Shuping Hu ◽  
Wei Jian ◽  
Chengjian Xie ◽  
Xingyong Yang
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Agricultural Production ◽  
Food Additives ◽  
Antimicrobial Activities ◽  
Gram Positive Bacteria ◽  
Potential Applications ◽  
Potential Applicability ◽  
Bacteria And Fungi ◽  
Positively Charged

AbstractAntimicrobial peptides (AMPs) are a class of short, usually positively charged polypeptides that exist in humans, animals, and plants. Considering the increasing number of drug-resistant pathogens, the antimicrobial activity of AMPs has attracted much attention. AMPs with broad-spectrum antimicrobial activity against many gram-positive bacteria, gram-negative bacteria, and fungi are an important defensive barrier against pathogens for many organisms. With continuing research, many other physiological functions of plant AMPs have been found in addition to their antimicrobial roles, such as regulating plant growth and development and treating many diseases with high efficacy. The potential applicability of plant AMPs in agricultural production, as food additives and disease treatments, has garnered much interest. This review focuses on the types of plant AMPs, their mechanisms of action, the parameters affecting the antimicrobial activities of AMPs, and their potential applications in agricultural production, the food industry, breeding industry, and medical field.

scholarly journals Long-term effects of the proline-rich antimicrobial peptide Oncocin112 on the Escherichia coli translation machinery

2020 ◽  
Vol 295 (38) ◽  
pp. 13314-13325
Author(s):  
Yanyu Zhu ◽  
James C. Weisshaar ◽  
Mainak Mustafi
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptides ◽  
Binding Site ◽  
Elongation Factor ◽  
Microscopy Study ◽  
Single Step ◽  
Long Term Effects ◽  
Bacterial Membranes

Proline-rich antimicrobial peptides (PrAMPs) are cationic antimicrobial peptides unusual for their ability to penetrate bacterial membranes and kill cells without causing membrane permeabilization. Structural studies show that many such PrAMPs bind deep in the peptide exit channel of the ribosome, near the peptidyl transfer center. Biochemical studies of the particular synthetic PrAMP oncocin112 (Onc112) suggest that on reaching the cytoplasm, the peptide occupies its binding site prior to the transition from initiation to the elongation phase of translation, thus blocking further initiation events. We present a superresolution fluorescence microscopy study of the long-term effects of Onc112 on ribosome, elongation factor-Tu (EF-Tu), and DNA spatial distributions and diffusive properties in intact Escherichia coli cells. The new data corroborate earlier mechanistic inferences from studies in vitro. Comparisons with the diffusive behavior induced by the ribosome-binding antibiotics chloramphenicol and kasugamycin show how the specific location of each agent's ribosomal binding site affects the long-term distribution of ribosomal species between 30S and 50S subunits versus 70S polysomes. Analysis of the single-step displacements from ribosome and EF-Tu diffusive trajectories before and after Onc112 treatment suggests that the act of codon testing of noncognate ternary complexes (TCs) at the ribosomal A-site enhances the dissociation rate of such TCs from their L7/L12 tethers. Testing and rejection of noncognate TCs on a sub-ms timescale is essential to enable incorporation of the rare cognate amino acids into the growing peptide chain at a rate of ∼20 aa/s.

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