scholarly journals Antibacterial Peptides

Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 142
Author(s):  
Jean-Marc Sabatier
Keyword(s):  
Antimicrobial Peptides ◽  
Host Defense ◽  
Life Forms ◽  
Natural Host ◽  
Gram Negative Bacteria ◽  
Antibacterial Peptides ◽  
Chemotherapeutic Drugs ◽  
Gram Positive ◽  
Defense Compounds ◽  
Gram Negative

As natural host defense compounds produced by numerous prokaryotic and eukaryotic life forms, antimicrobial peptides (AMPs) are now emerging as solid candidate chemotherapeutic drugs to fight against the various types of pathogenic Gram-positive and Gram-negative bacteria, especially those resistant to current antibiotics [...]

scholarly journals Cathelicidin Peptides Restrict Bacterial Growth via Membrane Perturbation and Induction of Reactive Oxygen Species

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Dean A. Rowe-Magnus ◽  
Adenine Y. Kao ◽  
Antonio Cembellin Prieto ◽  
Meng Pu ◽  
Cheng Kao
Keyword(s):  
Reactive Oxygen Species ◽  
Antimicrobial Peptides ◽  
Single Cell ◽  
Reactive Oxygen ◽  
Cellular Damage ◽  
Primary Effect ◽  
Gram Negative Bacteria ◽  
Oxygen Species ◽  
Gram Positive ◽  
Gram Negative

ABSTRACT All metazoans produce antimicrobial peptides (AMPs) that have both broad antimicrobial and immunomodulatory activity. Cathelicidins are AMPs that preferentially kill Gram-negative bacteria in vitro, purportedly by assembling into higher-order structures that perforate the membrane. We utilized high-resolution, single-cell fluorescence microscopy to examine their mechanism of action in real time. Engineered cathelicidins rapidly bound to Gram-negative and Gram-positive cells and penetrated the cytoplasmic membrane. Rapid failure of the peptidoglycan superstructure in regions of active turnover caused leakage of cytoplasmic contents and the formation of membrane-bound blebs. A mutation anticipated to destabilize interactions between cathelicidin subunits had no effect on bactericidal activity, suggesting that cathelicidins have activities beyond perforating the membrane. Nanomolar concentrations of cathelicidins, although not bactericidal, reduced the growth rate of Gram-negative and Gram-positive bacteria. The cells exhibited expression changes in multiple essential processes, including protein synthesis, peptidoglycan biosynthesis, respiration, and the detoxification of reactive oxygen species (ROS). Time-lapse imaging revealed that ROS accumulation preceded bleb formation, and treatments that reduced cellular ROS levels overcame these bactericidal effects. We propose that that the primary effect of cathelicidins is to induce the production of ROS that damage bacterial molecules, leading to slowed growth or cell death. Given their low circulating levels in vivo, AMPs may serve to slow bacterial population expansion so that cellular immunity systems can respond to and battle the infection. IMPORTANCE Antimicrobial peptides (AMPs) are an important part of the mammalian innate immune system in the battle against microbial infection. How AMPs function to control bacteria is not clear, as nearly all activity studies use nonphysiological levels of AMPs. We monitored peptide action in live bacterial cells over short time frames with single-cell resolution and found that the primary effect of cathelicidin peptides is to increase the production of oxidative molecules that cause cellular damage in Gram-positive and Gram-negative bacteria.

Characterization and identification of antimicrobial peptides with different functional activities

2019 ◽  
Vol 21 (3) ◽  
pp. 1098-1114 ◽  
Author(s):  
Chia-Ru Chung ◽  
Ting-Rung Kuo ◽  
Li-Ching Wu ◽  
Tzong-Yi Lee ◽  
Jorng-Tzong Horng
Keyword(s):  
Antimicrobial Peptides ◽  
Hot Spot ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Van Der Waals Volume ◽  
Gram Negative ◽  
Functional Activities ◽  
Wide Range ◽  
Anti Cancer ◽  
Anti Fungal

Abstract In recent years, antimicrobial peptides (AMPs) have become an emerging area of focus when developing therapeutics hot spot residues of proteins are dominant against infections. Importantly, AMPs are produced by virtually all known living organisms and are able to target a wide range of pathogenic microorganisms, including viruses, parasites, bacteria and fungi. Although several studies have proposed different machine learning methods to predict peptides as being AMPs, most do not consider the diversity of AMP activities. On this basis, we specifically investigated the sequence features of AMPs with a range of functional activities, including anti-parasitic, anti-viral, anti-cancer and anti-fungal activities and those that target mammals, Gram-positive and Gram-negative bacteria. A new scheme is proposed to systematically characterize and identify AMPs and their functional activities. The 1st stage of the proposed approach is to identify the AMPs, while the 2nd involves further characterization of their functional activities. Sequential forward selection was employed to extract potentially informative features that are possibly associated with the functional activities of the AMPs. These features include hydrophobicity, the normalized van der Waals volume, polarity, charge and solvent accessibility—all of which are essential attributes in classifying between AMPs and non-AMPs. The results revealed the 1st stage AMP classifier was able to achieve an area under the receiver operating characteristic curve (AUC) value of 0.9894. During the 2nd stage, we found pseudo amino acid composition to be an informative attribute when differentiating between AMPs in terms of their functional activities. The independent testing results demonstrated that the AUCs of the multi-class models were 0.7773, 0.9404, 0.8231, 0.8578, 0.8648, 0.8745 and 0.8672 for anti-parasitic, anti-viral, anti-cancer, anti-fungal AMPs and those that target mammals, Gram-positive and Gram-negative bacteria, respectively. The proposed scheme helps facilitate biological experiments related to the functional analysis of AMPs. Additionally, it was implemented as a user-friendly web server (AMPfun, http://fdblab.csie.ncu.edu.tw/AMPfun/index.html) that allows individuals to explore the antimicrobial functions of peptides of interest.

scholarly journals Physicochemical Properties That Enhance Discriminative Antibacterial Activity of Short Dermaseptin Derivatives

2006 ◽  
Vol 50 (8) ◽  
pp. 2666-2672 ◽  
Author(s):  
Shahar Rotem ◽  
Inna Radzishevsky ◽  
Amram Mor
Keyword(s):  
Antimicrobial Peptides ◽  
Physicochemical Properties ◽  
Culture Media ◽  
Gram Negative Bacteria ◽  
Terminal Sequence ◽  
Binding Properties ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Cytoplasmic Membranes

ABSTRACT Antimicrobial peptides are widely believed to exert their effects by nonspecific mechanisms. We assessed the extent to which physicochemical properties can be exploited to promote discriminative activity by manipulating the N-terminal sequence of the 13-mer dermaseptin derivative K4-S4(1-13) (P). Inhibitory activity determined in culture media against 16 strains of bacteria showed that when its hydrophobicity and charge were changed, P became predominantly active against either gram-positive or gram-negative bacteria. Thus, conjugation of various aminoacyl-lysin moieties (e.g., aminohexyl-K-P) led to inactivity against gram-positive bacteria (MIC50 > 50 μM) but potent activity against gram-negative bacteria (MIC50, 6.2 μM). Conversely, conjugation of equivalent acyls to the substituted analog M4-S4(1-13) (e.g., hexyl-M4-P) led to inactivity against gram-negative bacteria (MIC50 > 50 μM) but potent activity against gram-positive bacteria (MIC50, 3.1 μM). Surface plasmon resonance experiments, used to investigate peptides' binding properties to lipopolysaccharide-containing idealized phospholipid membranes, suggest that although the acylated derivatives have increased lipophilic properties with parallel antibacterial behavior, hydrophobic derivatives are prevented from reaching the cytoplasmic membranes of gram-negative bacteria. Moreover, unlike modifications that enhanced the activity against gram-positive bacteria, which also enhanced hemolysis, we found that modifications that enhanced activity against gram-negative bacteria generally reduced hemolysis. Thus, compared with the clinically tested peptides MSI-78 and IB-367, the dermaseptin derivative aminohexyl-K-P performed similarly in terms of potency and bactericidal kinetics but was significantly more selective in terms of discrimination between bacteria and human erythrocytes. Overall, the data suggest that similar strategies maybe useful to derive potent and safe compounds from known antimicrobial peptides.

scholarly journals Antimicrobial Peptide Resistance Genes in the Plant Pathogen Dickeya dadantii

2016 ◽  
Vol 82 (21) ◽  
pp. 6423-6430 ◽  
Author(s):  
Caroline Pandin ◽  
Martine Caroff ◽  
Guy Condemine
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Soft Rot ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Dickeya Dadantii ◽  
Gram Negative ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
New Genes

ABSTRACTModification of teichoic acid through the incorporation ofd-alanine confers resistance in Gram-positive bacteria to antimicrobial peptides (AMPs). This process involves the products of thedltXABCDgenes. These genes are widespread in Gram-positive bacteria, and they are also found in a few Gram-negative bacteria. Notably, these genes are present in all soft-rot enterobacteria (PectobacteriumandDickeya) whosedltDXBACoperons have been sequenced. We studied the function and regulation of these genes inDickeya dadantii.dltBexpression was induced in the presence of the AMP polymyxin. It was not regulated by PhoP, which controls the expression of some genes involved in AMP resistance, but was regulated by ArcA, which has been identified as an activator of genes involved in AMP resistance. However,arcAwas not the regulator responsible for polymyxin induction of these genes in this bacterium, which underlines the complexity of the mechanisms controlling AMP resistance inD. dadantii. Two other genes involved in resistance to AMPs have also been characterized,phoSandphoH.dltB,phoS,phoH, andarcAbut notdltDmutants were more sensitive to polymyxin than the wild-type strain. Decreased fitness of thedltB,phoS, andphoHmutants in chicory leaves indicates that their products are important for resistance to plant AMPs.IMPORTANCEGram-negative bacteria can modify their lipopolysaccharides (LPSs) to resist antimicrobial peptides (AMPs). Soft-rot enterobacteria (DickeyaandPectobacteriumspp.) possess homologues of thedltgenes in their genomes which, in Gram-positive bacteria, are involved in resistance to AMPs. In this study, we show that these genes confer resistance to AMPs, probably by modifying LPSs, and that they are required for the fitness of the bacteria during plant infection. Two other new genes involved in resistance were also analyzed. These results show that bacterial resistance to AMPs can occur in bacteria through many different mechanisms that need to be characterized.

scholarly journals Identification of Ly2 members as antimicrobial peptides from zebrafish Danio rerio

2017 ◽  
Vol 37 (1) ◽  
Author(s):  
Xuemin Liu ◽  
Xuwen Cao ◽  
Su Wang ◽  
Guangdong Ji ◽  
Shicui Zhang ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Recombinant Proteins ◽  
Mammalian Cells ◽  
Multidrug Resistant ◽  
Scatchard Analysis ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
Gram Positive Bacteria

The emergence of multidrug-resistant (MDR) microbes caused by overuse of antibiotics leads to urgent demands for novel antibiotics exploration. Our recent data showed that Ly2.1–3 (a novel lymphocyte antigen 6 (Ly6) gene cluster) were proteins with cationic nature and rich in cysteine content, that are characteristic of antimicrobial peptides (AMPs) and their expression were all significantly up-regulated after challenge with lipopolysaccharide (LPS). These strongly suggested that Ly2.1–3 are potential AMPs, but firm evidence are lacking. Here, we clearly showed that the recombinant proteins of Ly2.1–3 were capable of killing Gram-negative bacteria Aeromonas hydrophila and Escherichia coli, while they had little bactericidal activity against the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis. We also showed that recombinant proteins Ly2.1–3 (rLy2.1–3) were able to bind to the Gram-negative bacteria A. hydrophila, E. coli and the microbial signature molecule LPS, but not to the Gram-positive bacteria S. aureus and B. subtilis as well as the microbial signature molecule LTA. Moreover, the Scatchard analysis revealed that rLy2.1–3 could specifically bind to LPS. Finally, we found that Ly2.1–3 were not cytotoxic to mammalian cells. All these together indicate that Ly2.1–3 can function as AMPs.

scholarly journals Purification and Properties of Proline-Rich Antimicrobial Peptides from Sheep and Goat Leukocytes

1999 ◽  
Vol 67 (8) ◽  
pp. 4106-4111 ◽  
Author(s):  
Olga Shamova ◽  
Kim A. Brogden ◽  
Chengquan Zhao ◽  
Tung Nguyen ◽  
Vladimir N. Kokryakov ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Host Defense ◽  
Defense Mechanisms ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Purification And Properties

ABSTRACT We purified three proline-rich antimicrobial peptides from elastase-treated extracts of sheep and goat leukocytes and subjected two of them, OaBac5α and ChBac5, to detailed analysis. OaBac5α and ChBac5 were homologous to each other and to bovine Bac5. Both exhibited potent, broad-spectrum antimicrobial activity under low-concentration salt conditions. While the peptides remained active againstEscherichia coli, Pseudomonas aeruginosa,Bacillus subtilis, and Listeria monocytogenesin 100 mM NaCl, they lost activity against Staphylococcus aureus and Candida albicans under these conditions. ChBac5 was shown to bind lipopolysaccharide, a property that could enhance its ability to kill gram-negative bacteria. Proline-rich Bac5 peptides are highly conserved in ruminants and may contribute significantly to their innate host defense mechanisms.

scholarly journals Increasing the Antimicrobial Activity of Nisin-Based Lantibiotics against Gram-Negative Pathogens

2018 ◽  
Vol 84 (12) ◽  
Author(s):  
Qian Li ◽  
Manuel Montalban-Lopez ◽  
Oscar P. Kuipers
Keyword(s):  
Antimicrobial Peptides ◽  
Outer Membrane ◽  
Rational Design ◽  
Bacterial Species ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Lipid Ii

ABSTRACTLantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial compounds containing lanthionine and methyl-lanthionine residues. Nisin, one of the most extensively studied and used lantibiotics, has been shown to display very potent activity against Gram-positive bacteria, and stable resistance is rarely observed. By binding to lipid II and forming pores in the membrane, nisin can cause the efflux of cellular constituents and inhibit cell wall biosynthesis. However, the activity of nisin against Gram-negative bacteria is much lower than that against Gram-positive bacteria, mainly because lipid II is located at the inner membrane, and the rather impermeable outer membrane in Gram-negative bacteria prevents nisin from reaching lipid II. Thus, if the outer membrane-traversing efficiency of nisin could be increased, the activity against Gram-negative bacteria could, in principle, be enhanced. In this work, several relatively short peptides with activity against Gram-negative bacteria were selected from literature data to be fused as tails to the C terminus of either full or truncated nisin species. Among these, we found that one of three tails (tail 2 [T2; DKYLPRPRPV], T6 [NGVQPKY], and T8 [KIAKVALKAL]) attached to a part of nisin displayed improved activity against Gram-negative microorganisms. Next, we rationally designed and reengineered the most promising fusion peptides. Several mutants whose activity significantly outperformed that of nisin against Gram-negative pathogens were obtained. The activity of the tail 16 mutant 2 (T16m2) construct against several important Gram-negative pathogens (i.e.,Escherichia coli,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,Enterobacter aerogenes) was increased 4- to 12-fold compared to that of nisin. This study indicates that the rational design of nisin can selectively and significantly improve its outer membrane-permeating capacity as well as its activity against Gram-negative pathogens.IMPORTANCELantibiotics are antimicrobial peptides that are highly active against Gram-positive bacteria but that have relatively poor activity against most Gram-negative bacteria. Here, we modified the model lantibiotic nisin by fusing parts of it to antimicrobial peptides with known activity against Gram-negative bacteria. The appropriate selection of peptidic moieties that could be attached to (parts of) nisin could lead to a significant increase in its inhibitory activity against Gram-negative bacteria. Using this strategy, hybrids that outperformed nisin by displaying 4- to 12-fold higher levels of activity against relevant Gram-negative bacterial species were produced. This study shows the power of modified peptide engineering to alter target specificity in a desired direction.

scholarly journals Novel Cathelicidin Antimicrobial Peptides from Paa robertingeri

2019 ◽  
pp. 1-10
Author(s):  
Qinghua Luo ◽  
Huaiqing Deng ◽  
Mengguang Yin ◽  
Chen Chen ◽  
Jiang Zhou
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Hemolytic Activity ◽  
Fungal Species ◽  
Human Erythrocytes ◽  
Clinical Strain ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Novel Antibiotics

This study aimed to describe two cathelicidins (cathelicidin-PR1 and cathelicidin-PR2) from the skin of Paa robertingeri (Anura: Ranidae). The deduced mature peptides cathelicidin-PR1 and cathelicidin-PR2 were composed of 29 and 25 residues, respectively. Cathelicidin - PR1 has higher antimicrobial activity it could kill Gram-positive and Gram-negative bacteria and even some fungal species. Cathelicidin-PR1 exhibited more effective than AMP in antimicrobial activity against Pseydomonas maltophilia clinical strain. On the contrary, cathelicidin-PR2 had very weak antimicrobial activity. Furthermore, cathelicidin-PR1 and cathelicidin-PR2 exhibited very low hemolytic activity against human erythrocytes and little hemagglutinating activity. The results suggested that the cathelicidin-PR1 might serve as a template for developing novel antibiotics.

Rapid demonstration of septic or infectious arthritis due to Gram-negative bacteria

1992 ◽  
Vol 50 (1) ◽  
pp. 686-687
Author(s):  
Jacob S. Hanker ◽  
Paul R. Gross ◽  
Beverly L. Giammara
Keyword(s):  
Chronic Arthritis ◽  
Blood Cultures ◽  
Gram Negative Bacteria ◽  
Infectious Arthritis ◽  
Bacterial Arthritis ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

Blood cultures are positive in approximately only 50 per cent of the patients with nongonococcal bacterial infectious arthritis and about 20 per cent of those with gonococcal arthritis. But the concept that gram-negative bacteria could be involved even in chronic arthritis is well-supported. Gram stains are more definitive in staphylococcal arthritis caused by gram-positive bacteria than in bacterial arthritis due to gram-negative bacteria. In the latter situation where gram-negative bacilli are the problem, Gram stains are helpful for 50% of the patients; they are only helpful for 25% of the patients, however, where gram-negative gonococci are the problem. In arthritis due to gram-positive Staphylococci. Gramstained smears are positive for 75% of the patients.

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