scholarly journals Measuring thousands of single vesicle leakage events reveals the mode of action of antimicrobial peptides

2021 ◽  
Author(s):  
Kareem Al Nahas ◽  
Marcus Fletcher ◽  
Katharine Hammond ◽  
Christian Nehls ◽  
Jehangir Cama ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Host Defense ◽  
Mode Of Action ◽  
Antimicrobial Agents ◽  
Spatiotemporal Resolution ◽  
Detailed Understanding ◽  
Modes Of Action ◽  
Structure Activity ◽  
Single Vesicle

Host defense or antimicrobial peptides hold promise for providing new pipelines of effective antimicrobial agents. Their activity quantified against model phospholipid membranes is fundamental to a detailed understanding of their structure-activity relationships. However, existing characterization assays lack the resolution necessary to achieve this insight. Leveraging a highly parallelized microfluidic platform for trapping and studying thousands of giant unilamellar vesicles, we conducted quantitative long-term microscopy studies to monitor the membrane-disruptive activity of archetypal antimicrobial peptides with a high spatiotemporal resolution. We described the modes of action of these peptides via measurements of the disruption of the vesicle population under the conditions of continuous peptide dosing using a range of concentrations, and related the observed modes with the molecular activity mechanisms of these peptides. The study offers an effective approach for characterizing membrane-targeting antimicrobial agents in a standardized manner, and for assigning specific modes of action to the corresponding antimicrobial mechanisms.

scholarly journals A Review on Microorganisms-Derived Products as Potential Antimicrobial Agents

2021 ◽  
Author(s):  
Alka Rani ◽  
Khem Chand Saini ◽  
Felix Bast ◽  
Sunita Varjani ◽  
Sanjeet Mehariya ◽  
...  
Keyword(s):  
Cell Wall ◽  
Antimicrobial Peptides ◽  
Bioactive Compounds ◽  
Mode Of Action ◽  
Antimicrobial Agents ◽  
State Of The Art ◽  
Drug Resistant ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Streptomyces Sp

Microorganisms including actinomycetes, archaea, bacteria, fungi, yeast, and micro algae are the auspicious source of vital bioactive compounds. In this review, the existing state of the art re-garding antimicrobial molecules from microorganisms has been summarized. The potential an-timicrobial compounds from actinomycetes, particularly Streptomyces sp.; archaea; fungi including endophytic and marine-derived fungi, mushroom; yeast, and microalgae were briefly described. Furthermore, this review briefly summarized the activity and mode of action of bacteriocins, a ribosomally synthesized antimicrobial peptides product of Eurotium sp., Streptomyces parvulus, S. thermophiles, Lactococcus lactis, etc. Bacteriocins have inherent properties such as targeting multi-ple-drug resistant pathogens, which allows them to be considered next-generation antibiotics. Similarly, Glarea lozoyensis derived antifungal lipohexpeptides i.e., pneumocandins, inhibits 1,3-β-glucan synthase of the fungal cell wall and acts as a precursor for the synthesis of caspo-fungin, is also elaborated. In conclusion, this review highlights the possibility of using microor-ganisms as an antimicrobial resource for biotechnological, nutraceutical, and pharmaceutical ap-plications. However, more investigations are still required to separate, purify, and characterize these bioactive compounds and transfer these primary drugs into clinically approved antibiotics.

scholarly journals The Antimicrobial Activity of Cannabinoids

Antibiotics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 406
Author(s):  
John A. Karas ◽  
Labell J. M. Wong ◽  
Olivia K. A. Paulin ◽  
Amna C. Mazeh ◽  
Maytham H. Hussein ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Natural Products ◽  
Antimicrobial Agents ◽  
Cannabis Sativa ◽  
Antimicrobial Properties ◽  
Herbaceous Plant ◽  
Structure Activity Relationships ◽  
Modes Of Action ◽  
Structure Activity ◽  
Rapid Emergence

A post-antibiotic world is fast becoming a reality, given the rapid emergence of pathogens that are resistant to current drugs. Therefore, there is an urgent need to discover new classes of potent antimicrobial agents with novel modes of action. Cannabis sativa is an herbaceous plant that has been used for millennia for medicinal and recreational purposes. Its bioactivity is largely due to a class of compounds known as cannabinoids. Recently, these natural products and their analogs have been screened for their antimicrobial properties, in the quest to discover new anti-infective agents. This paper seeks to review the research to date on cannabinoids in this context, including an analysis of structure–activity relationships. It is hoped that it will stimulate further interest in this important issue.

scholarly journals Anti-Pseudomonas Activity of Frog Skin Antimicrobial Peptides in a Caenorhabditis elegans Infection Model: a Plausible Mode of Action In Vitro and In Vivo

2010 ◽  
Vol 54 (9) ◽  
pp. 3853-3860 ◽  
Author(s):  
Daniela Uccelletti ◽  
Elena Zanni ◽  
Ludovica Marcellini ◽  
Claudio Palleschi ◽  
Donatella Barra ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Antimicrobial Peptides ◽  
Mode Of Action ◽  
Frog Skin ◽  
Infection Model ◽  
Significant Activity ◽  
Experimental Conditions ◽  
Modes Of Action

ABSTRACT The emergence of multidrug-resistant (MDR) microorganisms makes it increasingly difficult to treat infections. These infections include those associated with Pseudomonas aeruginosa, which are hard to eradicate, especially in patients with a compromised immune system. Naturally occurring membrane-active cationic antimicrobial peptides (CAMPs) serve as attractive candidates for the development of new therapeutic agents. Amphibian skin is one of the richest sources for such peptides, but only a few studies on their in vivo activities and modes of action have been reported. We investigated (i) the activity and mechanism underlying the killing of short CAMPs from frog skin (e.g., temporins and esculentin fragments) on an MDR clinical isolate of P. aeruginosa and (ii) their in vivo antibacterial activities and modes of action, using the minihost model of Caenorhabditis elegans. Our data revealed that in vivo, both temporin-1Tb and esculentin(1-18) were highly active in promoting the survival of Pseudomonas-infected nematodes, although temporin-1Tb did not show significant activity in vitro under the experimental conditions used. Importantly, esculentin(1-18) permeated the membrane of Pseudomonas cells within the infected nematode. To the best of our knowledge, this is the first report showing the ability of a CAMP to permeate the microbial membrane within a living organism. Besides shedding light on a plausible mode of action of frog skin CAMPs in vivo, our data suggest that temporins and esculentins would be attractive molecules as templates for the development of new therapeutics against life-threatening infections.

Antimicrobial Peptides of Marine Crustaceans: The Potential and Challenges of Developing Therapeutic Agents

2018 ◽  
Vol 25 (19) ◽  
pp. 2245-2259 ◽  
Author(s):  
Negar T. Zanjani ◽  
Monica Miranda-Saksena ◽  
Anthony L. Cunningham ◽  
Fariba Dehghani
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Innate Immune System ◽  
Antimicrobial Agents ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Innate Immune ◽  
Genetic Composition ◽  
Structure Activity ◽  
Marine Crustaceans

The alarming increase of antimicrobial resistance has led to a growing number of studies aiming to develop novel antimicrobial therapeutics. Natural antimicrobial peptides possess a potent and broad-spectrum antimicrobial activity combined with diverse and unique structural motifs, which confer their different mechanisms of action. These peptides are ubiquitous in organisms and are integral to the innate immune system. Recently, identification of antimicrobial peptides from marine crustaceans has become the centre of attention of many researchers. This increasing interest stems from the remarkable diversity in the structural and genetic composition of these peptides compared to terrestrial counterparts. Thus, peptides from marine crustaceans can serve as future templates for novel antimicrobial agents. Here, we provide an overview of various antimicrobial peptides from the marine crustaceans, their antimicrobial activity and structure- activity relationships. We also discuss the potential and challenges of their development as new antimicrobial agents.

scholarly journals Fragments of the Nonlytic Proline-Rich Antimicrobial Peptide Bac5 KillEscherichia coliCells by Inhibiting Protein Synthesis

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Mario Mardirossian ◽  
Quentin Barrière ◽  
Tatiana Timchenko ◽  
Claudia Müller ◽  
Sabrina Pacor ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Antimicrobial Peptides ◽  
Binding Site ◽  
Mode Of Action ◽  
Antimicrobial Agents ◽  
Bacterial Membrane ◽  
Main Mode ◽  
Content Type ◽  
Inhibitor Of Protein Synthesis

ABSTRACTUnlike most antimicrobial peptides (AMPs), the main mode of action of the subclass of proline-rich antimicrobial peptides (PrAMPs) is not based on disruption of the bacterial membrane. Instead, PrAMPs exploit the inner membrane transporters SbmA and YjiL/MdtM to pass through the bacterial membrane and enter the cytosol of specific Gram-negative bacteria, where they exert an inhibitory effect on protein synthesis. Despite sharing a high proline and arginine content with other characterized PrAMPs, the PrAMP Bac5 has a low sequence identity with them. Here we investigated the mode of action of three N-terminal Bac5 fragments, Bac5(1-15), Bac5(1-25), and Bac5(1-31). We show that Bac5(1-25) and Bac5(1-31) retained excellent antimicrobial activity towardEscherichia coliand low toxicity toward eukaryotic cells, whereas Bac5(1-15) was inactive. Bac5(1-25) and Bac5(1-31) inhibited bacterial protein synthesisin vitroandin vivo. Competition assays suggested that the binding site of Bac5 is within the ribosomal tunnel, where it prevents the transition from the initiation to the elongation phase of translation, as reported for other PrAMPs, such as the bovine PrAMP Bac7. Surprisingly, unlike Bac7, Bac5(1-25) exhibited species-specific inhibition, being an excellent inhibitor of protein synthesis onE. coliribosomes but a poor inhibitor onThermus thermophilusribosomes. This indicates that while Bac5 most likely has an overlapping binding site with Bac7, the mode of interaction is distinct, suggesting that Bac5 fragments may be interesting alternative lead compounds for the development 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.

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