scholarly journals Engineering of Marine-derived Antimicrobial Peptides (mAMPs) into Improved Anti-infective Drug Leads: A Mini-review

2021 ◽  
Vol 1192 (1) ◽  
pp. 012013
Author(s):  
L Sukmarini
Keyword(s):  
Antimicrobial Peptides ◽  
Chemical Diversity ◽  
Cytotoxic Activities ◽  
Small Molecular Weight ◽  
Resistance Development ◽  
Drug Candidates ◽  
Bacteria And Fungi ◽  
Drug Leads ◽  
Net Positive Charge

Abstract Marine-derived antimicrobial compounds possess chemical diversity varying from peptides, fatty acids to terpenes, alkaloids, and polyketides. These compounds, especially of peptide origin called antimicrobial peptides (AMPs), are present in the majority of marine organisms, including microbes (bacteria and fungi), invertebrates (molluscs, echinoderms, and sponges), vertebrates (fish and mammals), and plants (marine algae). They are defined by small molecular weight (less than 10 kDa), a net positive charge, and amphipathic structures. Moreover, due to their profound in vitro antimicrobial and cytotoxic activities and a low risk for resistance development, naturally occurring marine-derived AMPs (mAMPs) have been used as drug design templates for a large variety of semi-synthetic or synthetic AMPs, some of which have reached clinical trials. This mini-review aims to discuss AMPs from marine sources, mainly emphasizing the engineering of these peptides with improved pharmacological properties to develop drug candidates. Some selected recent examples of these engineered mAMPs as anti-infective drug leads are herein highlighted.

scholarly journals Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Mark Austin Hanson ◽  
Anna Dostálová ◽  
Camilla Ceroni ◽  
Mickael Poidevin ◽  
Shu Kondo ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Fungal Pathogens ◽  
Gene Editing ◽  
Cationic Peptides ◽  
Gram Negative Bacteria ◽  
Biological Processes ◽  
Gram Negative ◽  
Bacteria And Fungi

Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These short, cationic peptides have been implicated in many biological processes, primarily involving innate immunity. In vitro studies have shown AMPs kill bacteria and fungi at physiological concentrations, but little validation has been done in vivo. We utilized CRISPR gene editing to delete most known immune-inducible AMPs of Drosophila, namely: 4 Attacins, 2 Diptericins, Drosocin, Drosomycin, Metchnikowin and Defensin. Using individual and multiple knockouts, including flies lacking these ten AMP genes, we characterize the in vivo function of individual and groups of AMPs against diverse bacterial and fungal pathogens. We found that Drosophila AMPs act primarily against Gram-negative bacteria and fungi, contributing either additively or synergistically. We also describe remarkable specificity wherein certain AMPs contribute the bulk of microbicidal activity against specific pathogens, providing functional demonstrations of highly specific AMP-pathogen interactions in an in vivo setting.

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 Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach

2018 ◽  
Author(s):  
Mark Austin Hanson ◽  
Anna Dostalova ◽  
Camilla Ceroni ◽  
Mickael Poidevin ◽  
Shu Kondo ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Fungal Pathogens ◽  
Gene Editing ◽  
Cationic Peptides ◽  
Gram Negative Bacteria ◽  
Biological Processes ◽  
Gram Negative ◽  
Bacteria And Fungi

Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These short, cationic peptides have been implicated in many biological processes, primarily involving innate immunity. In vitro studies have shown AMPs kill bacteria and fungi at physiological concentrations, but little validation has been done in vivo. We utilised CRISPR gene editing to delete all known immune inducible AMPs of Drosophila, namely: 4 Attacins, 4 Cecropins, 2 Diptericins, Drosocin, Drosomycin, Metchnikowin and Defensin. Using individual and multiple knockouts, including flies lacking all 14 AMP genes, we characterize the in vivo function of individual and groups of AMPs against diverse bacterial and fungal pathogens. We found that Drosophila AMPs act primarily against Gram-negative bacteria and fungi, acting either additively or synergistically. We also describe remarkable specificity wherein certain AMPs contribute the bulk of microbicidal activity against specific pathogens, providing functional demonstrations of highly specific AMP-pathogen interactions in an in vivo setting.

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.

Exploring Turkish biodiversity: A rich source of chemical diversity for drug leads discovery

2011 ◽  
Vol 83 (9) ◽  
pp. 1699-1707 ◽  
Author(s):  
Bilge Şener ◽  
İlkay Orhan
Keyword(s):  
Inhibitory Activity ◽  
Biological Activities ◽  
Chemical Diversity ◽  
Biological Investigation ◽  
Synthetic Drugs ◽  
Drug Molecules ◽  
Cholinesterase Inhibitory Activity ◽  
Plant Families ◽  
Drug Leads

Bioresources offer tremendous potential by having excellent chemical diversity for drug discovery programs and by serving as templates for synthetic drugs. There are well-known examples of clinically important drugs derived from natural sources. The development of pharmaceutical, nutraceutical, agricultural, and industrial products from bioresources can be used to promote incentives for conservation by providing an economic return to innovative use. Of those sources, medicinal plants have a virtually untapped reserve of original drug molecules, which await determination and chemical and biological investigation. Marine organisms have also gained increasing attention from researchers worldwide due to their chemically diverse secondary metabolites with desirable biological activities. There is still a great need for novel compounds with unique mechanisms of action to treat diseases such as cancer, Alzheimer’s, arthritis, and diabetes. Besides, multiresistance development by the parasites to the present drugs also constitutes another problem for the treatment of parasitic diseases as well as tuberculosis. In this article, 209 plant species belonging to 11 plant families were investigated for cholinesterase inhibitory activity by in vitro Ellman method at 10 μg/ml and 1 mg/ml doses. Among them, Salvia, Rosmarinus, and Fumaria species were found to have the most significant cholinesterase inhibitory activity.

A multifunctional molecular entity CuII–SnIV heterobimetallic complex as a potential cancer chemotherapeutic agent: DNA binding/cleavage, SOD mimetic, topoisomerase Iα inhibitory and in vitro cytotoxic activities

RSC Advances ◽  
2015 ◽  
Vol 5 (59) ◽  
pp. 47439-47450 ◽  
Author(s):  
Sartaj Tabassum ◽  
Ahmad Asim ◽  
Rais Ahmad Khan ◽  
Farukh Arjmand ◽  
Dhivya Rajakumar ◽  
...  
Keyword(s):  
Chemotherapeutic Agent ◽  
Schiff Base Complexes ◽  
Molecular Entity ◽  
Cytotoxic Activities ◽  
Chemotherapeutic Drug ◽  
Heterocyclic Ligand ◽  
Drug Candidates ◽  
Heterobimetallic Complex ◽  
Potential Cancer

New chiral l-valine-derived Schiff base complexes with the bioactive heterocyclic ligand scaffold pyrazole (Hpz) were designed and synthesized with a view to find their potential as anticancer chemotherapeutic drug candidates.

scholarly journals In silicoidentification of novel peptides with antibacterial activity against multidrug resistantStaphylococcus aureus

2019 ◽  
Author(s):  
Linda B Oyama ◽  
Hamza Olleik ◽  
Ana Carolina Nery Teixeira ◽  
Matheus M Guidini ◽  
James A Pickup ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptides ◽  
In Silico ◽  
Multidrug Resistant ◽  
Biofilm Inhibition ◽  
Methicillin Resistant ◽  
Drug Candidates ◽  
Wide Range

AbstractHerein we report the identification and characterisation of two linear antimicrobial peptides (AMPs), HG2 and HG4, with activity against a wide range of multidrug resistant (MDR) bacteria, especially methicillin resistantStaphylococcus aureus(MRSA) strains, a highly problematic group of Gram-positive bacteria in the hospital and community environment. To identify the novel AMPs presented here, we employed the classifier model design, a feature extraction method using molecular descriptors for amino acids for the analysis, visualization, and interpretation of AMP activities from a rumen metagenomic dataset. This allowed for thein silicodiscrimination of active and inactive peptides in order to define a small number of promising novel lead AMP test candidates for chemical synthesis and experimental evaluation.In vitrodata suggest that the chosen AMPs are fast acting, show strong biofilm inhibition and dispersal activity and are efficacious in anin vivomodel of MRSA USA300 infection, whilst showing little toxicity to human erythrocytes and human primary cell linesex vivo. Observations from biophysical AMP-lipid-interactions and electron microscopy suggest that the newly identified peptides interact with the cell membrane and may be involved in the inhibition of other cellular processes. Amphiphilic conformations associated with membrane disruption are also observed in 3D molecular modelling of the peptides. HG2 and HG4 both preferentially bind to MRSA total lipids rather than with human cell lipids indicating that HG4 may form superior templates for safer therapeutic candidates for MDR bacterial infections.Author SummaryWe are losing our ability to treat multidrug resistant (MDR) bacteria, otherwise known as superbugs. This poses a serious global threat to human health as bacteria are increasingly acquiring resistance to antibiotics. There is therefore urgent need to intensify our efforts to develop new safer alternative drug candidates. We emphasise the usefulness of complementing wet-lab andin silicotechniques for the rapid identification of new drug candidates from environmental samples, especially antimicrobial peptides (AMPs). HG2 and HG4, the AMPs identified in our study show promise as effective therapies for the treatment of methicillin resistantStaphylococcus aureusinfections bothin vitroandin vivowhilst having little cytotoxicity against human primary cells, a step forward in the fight against MDR infections.

scholarly journals In Vitro Evaluation of Antimicrobial Peptides from the Black Soldier Fly ( Hermetia Illucens ) against a Selection of Human Pathogens

2022 ◽  
Author(s):  
Laurence Van Moll ◽  
Jeroen De Smet ◽  
Anne Paas ◽  
Dorothee Tegtmeier ◽  
Andreas Vilcinskas ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Drug Development ◽  
Antimicrobial Peptides ◽  
Human Pathogens ◽  
Resistance Development ◽  
Black Soldier Fly ◽  
In Vitro Evaluation ◽  
Conventional Antibiotics ◽  
Selection Of

With the ever growing antimicrobial resistance, finding new candidates for antimicrobial drug development is indispensable. Antimicrobial peptides have steadily gained attention as alternatives for conventional antibiotics, due to some highly desirable characteristics, such as their low propensity for resistance development.

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