scholarly journals Antimicrobial peptides: mechanism of action and lipid-mediated synergistic interactions within membranes

2021 ◽  
Author(s):  
Dennis W. Juhl ◽  
Elise Glattard ◽  
Christopher Aisenbrey ◽  
Burkhard Bechinger

Biophysical and structural studies of peptide–lipid interactions, peptide topology and dynamics have changed our view of how antimicrobial peptides insert and interact with membranes.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tessa B. Moyer ◽  
Ashleigh L. Purvis ◽  
Andrew J. Wommack ◽  
Leslie M. Hicks

Abstract Background Plant defensins are a broadly distributed family of antimicrobial peptides which have been primarily studied for agriculturally relevant antifungal activity. Recent studies have probed defensins against Gram-negative bacteria revealing evidence for multiple mechanisms of action including membrane lysis and ribosomal inhibition. Herein, a truncated synthetic analog containing the γ-core motif of Amaranthus tricolor DEF2 (Atr-DEF2) reveals Gram-negative antibacterial activity and its mechanism of action is probed via proteomics, outer membrane permeability studies, and iron reduction/chelation assays. Results Atr-DEF2(G39-C54) demonstrated activity against two Gram-negative human bacterial pathogens, Escherichia coli and Klebsiella pneumoniae. Quantitative proteomics revealed changes in the E. coli proteome in response to treatment of sub-lethal concentrations of the truncated defensin, including bacterial outer membrane (OM) and iron acquisition/processing related proteins. Modification of OM charge is a common response of Gram-negative bacteria to membrane lytic antimicrobial peptides (AMPs) to reduce electrostatic interactions, and this mechanism of action was confirmed for Atr-DEF2(G39-C54) via an N-phenylnaphthalen-1-amine uptake assay. Additionally, in vitro assays confirmed the capacity of Atr-DEF2(G39-C54) to reduce Fe3+ and chelate Fe2+ at cell culture relevant concentrations, thus limiting the availability of essential enzymatic cofactors. Conclusions This study highlights the utility of plant defensin γ-core motif synthetic analogs for characterization of novel defensin activity. Proteomic changes in E. coli after treatment with Atr-DEF2(G39-C54) supported the hypothesis that membrane lysis is an important component of γ-core motif mediated antibacterial activity but also emphasized that other properties, such as metal sequestration, may contribute to a multifaceted mechanism of action.


Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 421
Author(s):  
Areetha R. D’Souza ◽  
Matthew R. Necelis ◽  
Alona Kulesha ◽  
Gregory A. Caputo ◽  
Olga V. Makhlynets

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.


2013 ◽  
Vol 1828 (8) ◽  
pp. 1802-1813 ◽  
Author(s):  
Evan F. Haney ◽  
Alexandra P. Petersen ◽  
Cheryl K. Lau ◽  
Weiguo Jing ◽  
Douglas G. Storey ◽  
...  

Peptides ◽  
2019 ◽  
Vol 114 ◽  
pp. 50-58 ◽  
Author(s):  
Flavia Anna Mercurio ◽  
Andrea Scaloni ◽  
Simonetta Caira ◽  
Marilisa Leone

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 801
Author(s):  
Guihong Pen ◽  
Na Yang ◽  
Da Teng ◽  
Ruoyu Mao ◽  
Ya Hao ◽  
...  

Viral infectious diseases pose a serious threat to animal husbandry, especially in the pig industry. With the rapid, continuous variation of viruses, a series of therapeutic measures, including vaccines, have quickly lost their efficacy, leading to great losses for animal husbandry. Therefore, it is urgent to find new drugs with more stable and effective antiviral activity. Recently, it has been reported that antimicrobial peptides (AMPs) have great potential for development and application in animal husbandry because of their significant antibacterial and antiviral activity, and the antiviral ability of AMPs has become a research hotspot. This article aims to review the research situation of AMPs used to combat viruses in swine production of animal husbandry, clarify the mechanism of action of AMPs on viruses and raise some questions, and explore the future potential of AMPs in animal husbandry.


Sign in / Sign up

Export Citation Format

Share Document