Showing papers on "Antimicrobial peptides published in 1993"
TL;DR: Porcine leukocytes contained three homologous peptides, PG‐1, 2 and 3, that manifested potent microbicidal activity against Escherichia coli, Listeria monocytogenes and Candida albicans in vitro.
491 citations
TL;DR: A new family of cysteine-rich antimicrobial peptides from bovine neutrophils was identified and characterized in this paper, and the peptides are characterized by a highly cationic 38-42-residue chain which includes 6 invariantly spaced cysteines which form three disulfides.
413 citations
TL;DR: The finding of an abundant defensin mRNA in human Paneth cells supports the notion that these epithelial cells may play a key role in host defense of the human bowel and strengthens the hypothesis that peptide‐based host defenses are prevalent at mucosal surfaces in mammals.
337 citations
TL;DR: The SapABCDF system constitutes a novel transporter for enteric bacteria and the first one harboring a periplasmic component with a role in virulence, and shows identity with other periplasmsic solute binding proteins involved in peptide transport.
Abstract: The innate immunity of vertebrates and invertebrates to microbial infection is mediated in part by small cationic peptides with antimicrobial activity. Successful pathogens have evolved mechanisms to withstand the antibiotic activity of these molecules. We have isolated a set of genes from Salmonella typhimurium which are required for virulence and resistance to the antimicrobial peptides melittin and protamine. Sequence analysis of a 5.7 kb segment from the wild-type plasmid conferring resistance to protamine contained five open reading frames: sapA, sapB, sapC, sapD and sapF, organized in an operon structure and transcribed as a 5.3 kb mRNA. SapD and SapF exhibited similarity with the 'ATP binding cassette' family of transporters including the bacterial Opp and SpoOK, involved in the uptake of oligopeptides; the yeast STE6, necessary for the export of a peptide pheromone; and the mammalian mdr, which mediates resistance to chemotherapeutic agents in cancer cells. SapA showed identity with other periplasmic solute binding proteins involved in peptide transport. The SapABCDF system constitutes a novel transporter for enteric bacteria and the first one harboring a periplasmic component with a role in virulence.
224 citations
TL;DR: The structural organization of the TAP gene is reported and it is shown that TAP is a member of a large family of related sequences with high nucleotide identity in the 5' exon, supporting the hypothesis that antimicrobial peptides contribute to host defense of the respiratory tract.
Abstract: We previously reported the isolation and characterization of a broad-spectrum antimicrobial peptide from the bovine tracheal mucosa, which we called tracheal antimicrobial peptide (TAP). We now show the TAP gene is expressed throughout the adult conducting airway, from nasal to bronchiolar tissue, but not in tissues other than airway mucosa, as determined by Northern blot analysis. In situ hybridization of airway sections localizes TAP mRNA to columnar cells of the pseudostratified epithelium. We report the structural organization of the TAP gene and show that TAP is a member of a large family of related sequences with high nucleotide identity in the 5' exon. The data support the hypothesis that antimicrobial peptides contribute to host defense of the respiratory tract.
157 citations
TL;DR: The peptides from R. esculenta show distinctive antibacterial activity against representative Gram‐negative and Gram‐positive bacterial species, and esculentin is the most active against Staphylococcus aureus, and has a much lower hemolytic activity.
134 citations
TL;DR: The cystine motif in BNBD-12 differs from that of classical defensin, and indicates that the beta-defensins and defensins must have differently folded chains, though they share several functional properties.
117 citations
TL;DR: Unlike previously characterized antimicrobial peptides derived from granulocyte proteins, CAP18(106-142) is active in serum and or a derivative peptide may have therapeutic potential for bacterial sepsis.
Abstract: A cationic antimicrobial protein of 18 kDa (CAP18) was originally isolated from rabbit granulocytes by using as an assay the agglutination of Re-lipopolysaccharide-coated erythrocytes. The C-terminal 37 amino acids of CAP18 (CAP18(106-142)) make up the lipopolysaccharide-binding domain. Synthetic CAP18(106-142) has broad antimicrobial activity against both gram-positive (50% inhibitory concentration, 130 to 200 nM) and gram-negative (50% inhibitory concentration, 20 to 100 nM) bacteria. Susceptible strains include Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhimurium. Antimicrobial activity is highly dependent on peptide structure. Although a 32-amino-acid peptide resulting from the truncation of 5 amino acids from the C terminus of CAP18(106-142) is highly active, other fragments of CAP18(106-142), including CAP18(106-142) with a truncated N terminus, do not exhibit antimicrobial activity. Unlike previously characterized antimicrobial peptides derived from granulocyte proteins, CAP18(106-142) is active in serum. CAP18(106-142) or a derivative peptide may have therapeutic potential for bacterial sepsis.
84 citations
TL;DR: The cDNA sequence of a 172 amino acid residue pig myeloid protein showing a similar pro-sequence of 101 residues is reported, identical to the mature form of the proline- and arginine-rich antibacterial peptide named PR-39, isolated from pig intestine.
79 citations
TL;DR: ProBac7 is a monocyte‐selective chemoattractant, potentially contributing to the recruitment of these cells to infection sites, whereas proBac5 efficiently inhibits the in vitro activity of cathepsin L, a cysteine proteinase thought to contribute to tissue injury in inflammation.
72 citations
TL;DR: A review of peptides synthesized by pathways that involve posttranslational modification of ribosomally synthesized precursor peptides for antimicrobial activity in prokaryotic and eukaryotic organisms and proposes future trends of research.
Abstract: Peptides that have antimicrobial activity are synthesized by many prokaryotic and eukaryotic organisms. Antimicrobial peptides commonly contain unusual amino acids that contribute to their properties and functions. Although bacteria synthesize most of these peptides by nonribosomal mechanisms, this review focuses on those that are synthesized by pathways that involve posttranslational modification of ribosomally synthesized precursor peptides. A particularly interesting class of these antimicrobial peptides is the lantibiotics, of which nisin and subtilin are the longest-known examples, although nearly a dozen new lantibiotics have been discovered in recent years. The fact that the lantibiotic structures are derived from gene-encoded peptides means that structural analogs of natural lantibiotics can be constructed by mutagenesis of their structural genes. Recent advances in our understanding of the molecular genetics of lantibiotics has made the construction of novel lantibiotics with enhanced chemical and antimicrobial properties possible. This review describes these advances and proposes future trends of research, as well as potential application of engineered lantibiotics, in the context of the general field of antimicrobial peptides.
TL;DR: A novel cDNA sequence of porcine bone marrow origin is reported, encoding a protein characterized by a cathelin-like domain that appears to be the precursor of a recently isolated antimicrobial peptide named protegrin PG-2.
TL;DR: Indolicidin and bactenecin might function as local regulators inhibiting clonal expansion of T lymphocytes during ongoing immune responses, and appear to be of limited potential as immunosuppressive agents in the treatment of autoimmune disease.
TL;DR: Small antimicrobial peptides are abundantly produced by leukocytes and are active against a broad range of pathogens, notably bacteria, fungi, and enveloped viruses, but hardly anything is known about their physiological and pathophysiological relevance.
Abstract: Small antimicrobial peptides are abundantly produced by leukocytes. These peptides are active against a broad range of pathogens, notably bacteria, fungi, and enveloped viruses, but hardly anything is known about their physiological and pathophysiological relevance. We observed that bactenecin, a dodecapeptide, is strongly cytotoxic to rat embryonic neurons, fetal rat astrocytes and human glioblastoma cells. This neurotoxicity is unique to bactenecin, as a panel of antibacterial peptides from vertebrates and invertebrates, like defensins, corticostatin, indolicidin, cecropin P1, tachyplesin I, the magainins, or apidaecins did not impair neuronal viability.
TL;DR: Structural and conformational homologies that are observed between adenoregulin and the dermaseptins, antimicrobial peptides exhibiting strong membranolytic activities against various pathogenic agents, suggest that adenorgulin is an additional member of the growing family of cytotropic antimicro peptides that allow vertebrate animals to defend themselves against microorganisms.
TL;DR: The phagocytic and microbicidal functions of neutrophils and macrophages provide an essential component of the host’s defense against colonization by a diverse spectrum of potential pathogens.
Abstract: Macrophages and neutrophils are phagocytic leukocytes of myeloid lineage, arising from hematopoietic precursors in the bone marrow. Neutrophils are short-lived cells which are terminally differentiated as they enter the circulation, whereas macrophages derive from circulating monocytes which mature into specialized cells in various tissues including lung, liver and skin. The phagocytic and microbicidal functions of neutrophils and macrophages provide an essential component of the host’s defense against colonization by a diverse spectrum of potential pathogens.
TL;DR: The designed cyclic model peptides show antibacterial activity but accompany no hemolysis indicates that an appropriate hydrophobicity together with a proper orientation of hydrophilic and hydrophobic groups in cyclic beta-structural molecules can hold antimicrobial activity against both types of bacteria without damaging eukaryotic cells.
TL;DR: Experiments with C18G and 399 revealed that their activity was indeed reduced in the presence of human serum, but that significant lytic activity remained even at relatively high serum concentrations, and low-density lipoprotein was found to be a potent inhibitor of peptide-mediated cell lysis.
Abstract: Antimicrobial peptides that can form amphiphilic alpha helices were tested for their ability to lyse various human tumor cell lines in vitro. These peptides include C18G, whose sequence is a derivative of the carboxyl terminus of human platelet factor IV, and 399, an idealized amphiphilic alpha helix. Both peptides exhibited potent antitumor activity against all cell lines tested, unlike magainin 2, a naturally occurring antimicrobial peptide of similar structure, which was relatively inactive under the same conditions. Also, the lytic activity of C18G is specific for tumor cells versus human red blood cells. The effects of serum can be important when evaluating the potency of lytic peptides, since other tumoricidal peptides have been shown to be completely inactivated by low serum levels. Experiments with C18G and 399 revealed that their activity was indeed reduced in the presence of human serum, but that significant lytic activity remained even at relatively high serum concentrations. Various serum components were tested for their inhibitory activity. Whereas albumin and high-density lipoprotein had only slight inhibitory properties, low-density lipoprotein was found to be a potent inhibitor of peptide-mediated cell lysis. The peptide 399, which is more sensitive to serum inhibition than C18G, also binds more extensively to all serum components tested.
Patent•
09 Dec 1993
TL;DR: In this paper, the use of these antimicrobial peptides to provide organisms, and, in particular, plants, with protection from microbial pathogens is discussed, and a screening method which may be useful for determining the phytotoxity of an antimacterial peptide is proposed.
Abstract: The present invention relates to several types of antimicrobial peptides including reverse antimicrobial peptides, antimicrobial oligopeptides and other antimicrobial compositions, such as cecropin P1. The present invention also relates to the use of these antimicrobial peptides to provide organisms, and, in particular, plants, with protection from microbial pathogens. Finally, the present invention relates to a screening method which may be useful for determining the phytotoxity of an antimicrobial peptide.
TL;DR: Bac5 and Bac7 are antimicrobial peptides of bovine neutrophils that act on enteric gram-negative bacteria and, although both peptides bind to Borrelia burgdorferi, the organism is resistant to their action.
Abstract: Bac5 and Bac7 are antimicrobial peptides of bovine neutrophils that act on enteric gram-negative bacteria. We report here that these two peptides immobilize and kill Leptospira interrogans and Leptospira biflexa with MBCs of 6 to 25 micrograms/ml. Conversely, although both peptides bind to Borrelia burgdorferi, the organism is resistant to their action.
TL;DR: The magainins (or magainin analogues) are the most advanced in terms of commercial development and have a greater chance of reaching the clinic than do other host defence peptides.
Abstract: Recently a number of endogenous host defence molecules with antimicrobial activity have been identified in mammals, invertebrates and amphibians (for reviews see Ganz, Selsted Within this group of anti-microbial agents there are several small peptides (2-4K.) that include the defensins (found predominantly in mammalian phago-cytes), cecropins, diptericins, attacins, apidae-cins, abaecin, royalisin (all from insect sources) and the magainins (amphibian source). A number of semi-synthetic magainins are currently under development as topical anti-microbial agents with potential dermatolo-gical, ophthalmic and periodontal applications (Anonymous, 1992). This article briefly reviews the current status of the magainins, and considers the structure, mode of action and antimicrobial spectrum of these peptides. Amongst the defensins, the magainins (or magainin analogues) are the most advanced in terms of commercial development (Rennie, 1993). It is for this reason that this article focuses on the magainins since they have a greater chance of reaching the clinic than do other host defence peptides. Magainins were identified in the skin secretions of the African clawed frog, Xenopus laevis, by Zasloff and co-workers (Zasloff, 1987; Zasloff, Martin & Chen, 1988). These host defense peptides are secreted by granular glands in the skin of the frog in response to tissue injury (MacDonald, Berkowitz & Jacob, 1990). Magainins 1 and 2 (mgn 1 and 2) (also known as PGS-peptides beginning with glycine and ending with serine) are 23 residue peptides with the following sequences (Zasloff el al., (peptide beginning with glycine and ending with leucine amide), is another antimicrobial peptide (21 residues) isolated from frog skin (Williams et al. Little sequence homology with mgnl or mgn2 these peptides are all positively charged and can form amphiphilic helices about 30 A in length (Williams et al., 1990). Because these features are common to polypeptides that bind to lipid bilayers it has been suggested that magainins and PGLa act as transmembrane helical channel former that dissipate the membrane potential (Zasloff, 1987). Subsequent membrane depolarization studies in Escherichia coli using tetraphenyl phosphonium ion (TPP +) to measure the membrane potential have indeed confirmed that mgn2 and PGLa dissipate the membrane potential (Westerhoff et al., 1989; Jurectic, 1990). Although mgnl was not specifically examined in these studies (Westerhoff et al., 1989; Jurectic, 1990) its structural similarity to mgn2 implies a similar mode of action. Antimicrobial agents that dissipate the membrane potential invariably have secondary effects on bacterial metabolism leading to stimulation of autolytic enzyme activity, bacterial lysis and cell …
Patent•
11 May 1993TL;DR: In this article, a new class of polypeptides with antimicrobial activity, termed tracheal antimicrobial peptides (tracheal ACP), were proposed. But their methods for the production and use of the peptides were not described.
Abstract: The present invention provides a new class of polypeptides with antimicrobial activity, termed "tracheal antimicrobial peptides," DNA and cDNA sequences encoding for the peptides and methods for the production and use thereof.
Patent•
26 Mar 1993TL;DR: In this article, the authors proposed a method to synthesize hybrid peptides, which are a mixture of naturally occurring peptides such as cecropins, attacins, magainins, sarcotoxin, sapecin, bactenecins, alamethidicins, defensins and PGLa, and toxins such as streptolysins, melittin, barbatolysin, paradaxins and delta hemolysin.
Abstract: The invention relates to antibacterial and antimalarial peptides which are hybrids peptides which a of naturally occurring peptides such as cecropins, attacins, magainins, sarcotoxin, sapecin, bactenecins, alamethidicins, defensins and PGLa, and toxins such as streptolysins, melittin, barbatolysin, paradaxins and delta hemolysin. The hybrid peptides of the present invention are easily synthesized and have reduced toxicity. Also included in the invention are pharmaceutical compositions containing such hybrid peptides, and methods of treating patients infected with an organism against which these peptides are active.
TL;DR: It is concluded that charge distribution, but not chirality or net charge, is an important determinant in the antibiotic efficacy of IIGGR, and peptide antibiotics derived from cathepsin G may have therapeutic value against periodontal gram-negative, facultative bacteria.
Abstract: Actinobacillus actinomycetemcomitans and Capnocytophaga spp. are gram-negative bacteria implicated in the etiology of periodontal disease (particularly in individuals with neutrophil defects) and life-threatening systemic infections. They are resistant to many antibiotics of microbial origin but are sensitive to the nonoxidative microbicidal action of neutrophils. These organisms are susceptible to the microbicidal effect of cathepsin G but are killed by two distinct mechanisms. The purpose of this study was to assess their sensitivity to the antibiotic effects of IIGGR and HPQYNQR, antimicrobial peptides derived from human neutrophil cathepsin G. The efficacies of the synthetic peptides IIGGR and HPQYNQR were tested by single-dose screening, dose-response, and kinetic assays against three representative strains (each) of A. actinomycetemcomitans and Capnocytophaga spp. and one strain of Eikenella corrodens. Strains of A. actinomycetemcomitans were sensitive to IIGGR and HPQYNQR at equal concentrations (wt/vol), whereas strains of Capnocytophaga and E. corrodens were more sensitive to IIGGR than to HPQYNQR. These differential antibiotic effects occurred over both time and dose ranges too narrow to be of therapeutic significance but are consistent with the premise that cathepsin G kills these oral bacteria by two distinct mechanisms. Except for IVGGR, congeners of IIGGR, including AIGGR, IAGGR, IIAGR, IIGAR, IIGGA, IQGGR, ILGGR, and I-norleucyl-GGR (InLGGR), were microbicidal at 500 micrograms/ml. IIGGR-amide exhibited no antibiotic activity. The D-enantiomer of IIGGR, DIDIGGDR, was as potent as IIGGR itself. APQYNQR exhibited antibiotic activity but somewhat less than HPQYNQR. We conclude that charge distribution, but not chirality or net charge, is an important determinant in the antibiotic efficacy of IIGGR. Moreover, peptide antibiotics derived from cathepsin G may have therapeutic value against periodontal gram-negative, facultative bacteria.
Patent•
19 Mar 1993TL;DR: In this article, a new family of cysteine-rich antimicrobial peptides isolated from bovine neutrophils was presented, named beta defensins. And thirteen structurally homologous peptides were purified to homogeneity from a granule-rich cytoplasmic fraction of purified blood neutrophILS.
Abstract: The present invention provides a new family of cysteine-rich antimicrobial peptides isolated from bovine neutrophils herein named beta defensins. Thirteen structurally homologous peptides were purified to homogeneity from a granule-rich cytoplasmic fraction of purified blood neutrophils. These antimicrobial compounds are useful in human and veterinary medicine, and as agents in agricultural, food science, and industrial applications.
Journal Article•
01 Jan 1993
TL;DR: Mortkawa et al. as mentioned in this paper described three peptides from a Japanese frog, two of which are similar to brevinm-1 and two of them are different types of peptides, one is 46 residues long and represents a different type of peptide.
Abstract: Two of them show similarity to brevinm-1 and brevinm-2. respectively. two antimrcrobial peptides recently isolated from a Japanese frog [Mortkawa. N., Hagiwara, K. and Nakajima. T. (1992) Biochem. Biophys. Res. Commun 189. 1841901. The third one, named esculentin, is 46 residues long and represents a different type of peptide. All these peptides have as a common motif an intramolecular dtsulfide bridge located at the COOH-terminal end. The peptides from
01 Jan 1993