scholarly journals Beneficial Impacts of Incorporating the Non-Natural Amino Acid Azulenyl-Alanine into the Trp-Rich Antimicrobial Peptide buCATHL4B

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 421
Author(s):  
Areetha R. D’Souza ◽  
Matthew R. Necelis ◽  
Alona Kulesha ◽  
Gregory A. Caputo ◽  
Olga V. Makhlynets
Keyword(s):  
Amino Acid ◽  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Mechanism Of Action ◽  
Bactericidal Activity ◽  
Antimicrobial Agents ◽  
Human Cells ◽  
Side Chains ◽  
Natural Amino Acid ◽  
Proteolytic Stability

Antimicrobial peptides (AMPs) present a promising scaffold for the development of potent antimicrobial agents. Substitution of tryptophan by non-natural amino acid Azulenyl-Alanine (AzAla) would allow studying the mechanism of action of AMPs by using unique properties of this amino acid, such as ability to be excited separately from tryptophan in a multi-Trp AMPs and environmental insensitivity. In this work, we investigate the effect of Trp→AzAla substitution in antimicrobial peptide buCATHL4B (contains three Trp side chains). We found that antimicrobial and bactericidal activity of the original peptide was preserved, while cytocompatibility with human cells and proteolytic stability was improved. We envision that AzAla will find applications as a tool for studies of the mechanism of action of AMPs. In addition, incorporation of this non-natural amino acid into AMP sequences could enhance their application properties.

Molecular characterization of lingual antimicrobial peptide gene of local cattle (Bos indicus) of Assam and insilco designing of antimicrobial peptides

2018 ◽  
Author(s):  
D. J. Kalita ◽  
S. Sarma ◽  
A. Baruah
Keyword(s):  
Amino Acid ◽  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Antimicrobial Agents ◽  
Bos Indicus ◽  
Amino Acid Sequences ◽  
Support Vector ◽  
Mature Peptide ◽  
Pcr Product ◽  
Peptide Gene

Mammalian defensin is the one of the important antimicrobial peptides expressed by different epithelial lining of the living organisms. Present study was undertaken to characterize the lingual antimicrobial peptide (LAP) gene of Assam local cattle (Bos indicus ) for insilco designing of peptide for synthesis of novel antimicrobial agents. RNA was isolated from the tongue epithelial of Bos indicus and reverse transcribed with specific primer. The amplified PCR product was purified, cloned and sequenced. The size of the PCR product was 230 bp and cloned cDNA after sequencing revealed the open reading frame (ORF) of 195 bases. The total number of predicted amino acid in the peptide was 64. Aligned amino acid sequences of Bos indicus LAP showed six conserved cysteine residues at different positions. The mature peptide of local cattle LAP had six (6) arginine, three (3) lysine, three (3) proline and one (1) histidin residues. Support vector machine algorithms showed the antimicrobial potency of different segments of the mature peptide and out of them four different most potent peptides were designed. From the present study, it can be concluded that the mature domain of the Bos indicus lingual antimicrobial peptide (LAP) may be use as template for synthesis of new antimicrobial agents.

Antimicrobial Peptides: A Promising Avenue for Human Healthcare

2020 ◽  
Vol 21 (2) ◽  
pp. 90-96 ◽  
Author(s):  
Girish M. Bhopale
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Antimicrobial Agents ◽  
Current Status ◽  
Antimicrobial Drugs ◽  
Spectrum Activity ◽  
Low Levels ◽  
Human Healthcare ◽  
Broad Spectrum Activity ◽  
Promising Avenue

Antimicrobial drugs resistant microbes have been observed worldwide and therefore alternative development of antimicrobial peptides has gained interest in human healthcare. Enormous progress has been made in the development of antimicrobial peptide during the last decade due to major advantages of AMPs such as broad-spectrum activity and low levels of induced resistance over the current antimicrobial agents. This review briefly provides various categories of AMP, their physicochemical properties and mechanism of action which governs their penetration into microbial cell. Further, the recent information on current status of antimicrobial peptide development, their applications and perspective in human healthcare are also described.

scholarly journals Cathelicidin Antimicrobial Peptides with Reduced Activation of Toll-Like Receptor Signaling Have Potent Bactericidal Activity against Colistin-Resistant Bacteria

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Cheng Kao ◽  
Xiaoyan Lin ◽  
Guanghui Yi ◽  
Yunliang Zhang ◽  
Dean A. Rowe-Magnus ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Bactericidal Activity ◽  
Bacterial Infections ◽  
Inflammatory Responses ◽  
Human Cells ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Human Red Blood Cells ◽  
Minor Injuries

ABSTRACT The world is at the precipice of a postantibiotic era in which medical procedures and minor injuries can result in bacterial infections that are no longer effectively treated by antibiotics. Cathelicidins are peptides produced by animals to combat bacterial infections and to regulate innate immune responses. However, cathelicidins are potent activators of the inflammatory response. Cathelicidins with reduced proinflammatory activity and potent bactericidal activity in the low micromolar range against Gram-negative bacteria have been identified. Motifs in cathelicidins that impact bactericidal activity and cytotoxicity to human cells have been elucidated and used to generate peptides that have reduced activation of proinflammatory cytokine production and reduced cytotoxicity to human cells. The resultant peptides have bactericidal activities comparable to that of colistin and can kill colistin-resistant bacteria. IMPORTANCE Cathelicidins are antimicrobial peptides that can also increase inflammatory responses. This combination of activities can cause complications in the treatment of bacterial infections despite the pressing need for new antimicrobials. We have identified cathelicidins with decreased activation of inflammatory responses. The peptides kill Gram-negative bacteria at low micromolar concentrations by binding to and perturbing the integrity of the bacterial membrane. The peptides were also engineered to further decrease lysis of human red blood cells. The peptides have activities comparable to those of the polymyxins, a class of antibiotics to which plasmid-borne resistance is rapidly spreading and can kill colistin-resistant bacteria. These peptides are promising candidates for the development of novel antibacterial agents.

scholarly journals A Uniform In Vitro Efficacy Dataset to Guide Antimicrobial Peptide Design

Data ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 27 ◽  
Author(s):  
Deepesh Nagarajan ◽  
Tushar Nagarajan ◽  
Neha Nanajkar ◽  
Nagasuma Chandra
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Antimicrobial Agents ◽  
Multi Drug Resistance ◽  
Peptide Design ◽  
Drug Candidates ◽  
The Face ◽  
Conventional Antibiotics ◽  
Different Sources

Antimicrobial peptides are ubiquitous molecules that form the innate immune system of organisms across all kingdoms of life. Despite their prevalence and early origins, they continue to remain potent natural antimicrobial agents. Antimicrobial peptides are therefore promising drug candidates in the face of overwhelming multi-drug resistance to conventional antibiotics. Over the past few decades, thousands of antimicrobial peptides have been characterized in vitro, and their efficacy data are now available in a multitude of public databases. Computational antimicrobial peptide design attempts typically use such data. However, utilizing heterogenous data aggregated from different sources presents significant drawbacks. In this report, we present a uniform dataset containing 20 antimicrobial peptides assayed against 30 organisms of Gram-negative, Gram-positive, mycobacterial, and fungal origin. We also present circular dichroism spectra for all antimicrobial peptides. We draw simple inferences from this data, and we discuss what characteristics are essential for antimicrobial peptide efficacy. We expect our uniform dataset to be useful for future projects involving computational antimicrobial peptide design.

scholarly journals A uniform in vitro efficacy dataset to guide antimicrobial peptide design

2018 ◽  
Author(s):  
Deepesh Nagarajan ◽  
Tushar Nagarajan ◽  
Neha Nanajkar ◽  
Nagasuma Chandra
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Antimicrobial Agents ◽  
Multi Drug Resistance ◽  
Peptide Design ◽  
Drug Candidates ◽  
The Face ◽  
Conventional Antibiotics ◽  
Different Sources

ABSTRACTAntimicrobial peptides are ubiquitous molecules that form the innate immune system of organisms across all kingdoms of life. Despite their prevalence and early origins, they continue to remain potent natural antimicrobial agents. Antimicrobial peptides are therefore promising drug candidates in the face of overwhelming multi-drug resistance to conventional antibiotics. Over the past few decades, thousands of antimicrobial peptides have been characterized in vitro, and their efficacy data is now available in a multitude of public databases. Computational antimicrobial peptide design attempts typically use such data. However, utilizing heterogenous data aggregated from different sources presents significant drawbacks. In this report, we present a uniform dataset containing 20 antimicrobial peptides assayed against 30 organisms spanning gram positive, gram negative, fungal, and mycobacterial origin. We draw inferences from the results of 600 individual MIC assays, and discuss what characteristics are essential for antimicrobial peptide efficacy. We expect our uniform dataset to be useful for future projects involving computational antimicrobial peptide design.

Antimicrobial peptide bsn-37 inhibits the growth of Escherichia coli by targeting its cell wall and membrane

2020 ◽  
Vol 10 (8) ◽  
pp. 1260-1264
Author(s):  
Jingyu Fu ◽  
Hao Yang ◽  
Hongliang Wang ◽  
Jun Ke ◽  
Debao Kong
Keyword(s):  
Escherichia Coli ◽  
Cell Wall ◽  
Antimicrobial Peptides ◽  
Nucleic Acids ◽  
Antimicrobial Peptide ◽  
Mechanism Of Action ◽  
E Coli ◽  
Colony Counting ◽  
Kinetics Of ◽  
Growth And Reproduction

To understand the mechanism of action of the antimicrobial peptide bsn-37 on Escherichia coli (E. coli), we investigated its effects on leakage of ultraviolet-absorbing substances, proteins, and nucleic acids from E. coli CVCC1568. The bacteriostatic kinetics of antimicrobial peptides was determined by colony counting. Our study showed that bsn-37 could effectively inhibit the growth and reproduction of E. coli by disrupting its cell wall and membrane.

scholarly journals Improving the Activity of Antimicrobial Peptides Against Aquatic Pathogen Bacteria by Amino Acid Substitutions and Changing the Ratio of Hydrophobic Residues

2021 ◽  
Vol 12 ◽  
Author(s):  
Rong Tan ◽  
Meiru Wang ◽  
Huiqin Xu ◽  
Lu Qin ◽  
Jun Wang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Antimicrobial Peptides ◽  
Antimicrobial Agents ◽  
Micrococcus Luteus ◽  
Vibrio Anguillarum ◽  
Intestinal Flora ◽  
Resistant Bacteria ◽  
Optimization Strategy ◽  
Drug Resistant Bacteria ◽  
The Stability

With the increasing number of drug-resistant bacteria, there is an urgent need for new antimicrobial agents, and antimicrobial peptides (AMPs), which exist in the human non-specific immune system, are one of the most promising candidates. It is an effective optimization strategy to modify antimicrobial peptides (AMPs) according to the distribution of amino acids and hydrophobic characteristics. The addition of bacterial pheromones to the N short peptide can increase the ability to recognize bacteria. In this study, we designed and synthesized AMP1–6 by amino acid substitution of mBjAMP1. Additionally, P-6, S-6, and L-6 were designed and synthesized by adding bacterial pheromones based on 1–6. Functional tests showed that the four AMPs had the ability to kill Gram-negative Vibrio anguillarum, Pseudomonas mendocina, and Vibrio parahaemolyticus, and Gram-positive Micrococcus luteus and Listeria monocytogenes. Additionally, all four AMPs induced permeabilization and depolarization of bacterial cell membranes and increased intracellular reactive oxygen species (ROS) levels. Importantly, they had little or no mammalian cytotoxicity. At the same time, 1–6 and L-6 protected the stability of intestinal flora in Sebastes schlegelii and increased the relative abundance of Lactobacillaceae. In summary, our results indicate that the designed AMPs have broad application prospects as a new type of polypeptide antimicrobial agent.

scholarly journals Dimerization of Antimicrobial Peptides: A Promising Strategy to Enhance Antimicrobial Peptide Activity

2019 ◽  
Vol 26 (2) ◽  
pp. 98-107 ◽  
Author(s):  
Esteban N. Lorenzon ◽  
Julia P. Piccoli ◽  
Norival A. Santos-Filho ◽  
Eduardo M. Cilli
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Mechanism Of Action ◽  
Antimicrobial Agents ◽  
Membrane Disruption ◽  
Promising Strategy ◽  
Peptide Dimerization ◽  
The Relationship ◽  
Intracellular Targets ◽  
Global Health Problem

Antimicrobial resistance is a global health problem with strong social and economic impacts. The development of new antimicrobial agents is considered an urgent challenge. In this regard, Antimicrobial Peptides (AMPs) appear to be novel candidates to overcome this problem. The mechanism of action of AMPs involves intracellular targets and membrane disruption. Although the exact mechanism of action of AMPs remains controversial, most AMPs act through membrane disruption of the target cell. Several strategies have been used to improve AMP activity, such as peptide dimerization. In this review, we focus on AMP dimerization, showing many examples of dimerized peptides and their effects on biological activity. Although more studies are necessary to elucidate the relationship between peptide properties and the dimerization effect on antimicrobial activity, dimerization constitutes a promising strategy to improve the effectiveness of AMPs.

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