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Antimicrobial Peptides: Structure and Mechanism of Biological Activity

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 39198

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Prof. Dr. Masoud Jelokhani-Niaraki

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Department of Chemistry & Biochemistry, Wilfrid Laurier University, Waterloo, ON, Canada
Interests: biophysical chemistry of membrane proteins and membrane interacting peptides; peptide and protein ion transport; antimicrobial peptides
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Dear Colleagues,

Since the early 1960s, the resistance of microbes against antibiotics has been recognized as a potential global health issue. This issue is now critical due to the reemergence of several infectious diseases of microbial origin and prevalence of multidrug-resistant microbes. Antimicrobial peptides (AMPs) have offered a good potential for novel drugs against drug-resistant microbial organisms, and extensive research has been dedicated to the discovery, characterization, de novo design, and assessment of the antimicrobial activity of these peptides since the late 1980s. So far, more than 3000 AMPs have been characterized and documented. These peptides have diverse natural origins and are found in unicellular organisms (bacteria, archaea, protists, and fungi), plants, and animals. Close to 75% of AMPs are found in animals, ~11% in plants, and about the same number in bacteria. Based on the sequences of these naturally found peptides, new chemically modified synthetic peptides have been designed to enhance or modify the biological activity of the original peptides. AMPs are also diverse in their biological activities and can be multifunctional. In addition to their antimicrobial activity, AMPs can have other biological functions, such as antioxidant, anticancer, antimalarial, chemotactic (modulation of immune systems), and wound healing. The diversity of AMPs expands to their physicochemical properties, structure, and mechanism of biological activity, which are the foci of this Special Issue. Most, but not all, AMPs are positively charged, and negatively and neutrally charged peptides can also be found. AMPs have different structures (α-helix, β-sheet, turn, or nonspecific interconvertible dynamic structures), overall hydrophobicity and amphipathicity, and can be linear, cyclic, or a combination of both. Many AMPs interact with the lipid membranes of the microbial/nonmicrobial cells and destroy these cells by disrupting the osmotic balance across the membrane. Some AMPs can pass across cell membranes and interact with intracellular targets such as organelle membranes, receptor proteins, or DNA.

In the late 1980s and during the 1990s, several models were proposed for the mechanism of interaction of AMPs with model cell membranes, which generally include self-association of peptides and/or peptide–lipid association from specific well-defined pores or to induce nonspecific leakage. The mechanisms of translocation of AMPs through cell membranes and their successive interaction with intracellular molecules are less investigated. Understanding and visualizing the structural dynamics (subtle and fast conformational changes prior to and after interaction with cell membranes) and the entirety of the complex biophysical nature of the mechanism of the biological activity of AMPs are essential steps toward the discovery and design of new antimicrobial peptide drugs.

Prof. Dr. Masoud Jelokhani-Niaraki
Guest Editor

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Keywords

antimicrobial peptides
mechanism of biological activity
functional diversity of peptides
structural analysis of peptides
dynamic conformation of peptides
lipid composition of the cell membrane
peptide–lipid interactions
peptide self-association
peptide-lipid complex formation
peptide–intracellular receptor interaction
peptide translocation through membrane
cell morphology
peptide interaction with infectious agents
surface properties of the cell
peptide interaction with the cell in vivo

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15 pages, 1683 KiB

Open AccessArticle

The Inhibition of DNA Viruses by the Amphibian Antimicrobial Peptide Temporin G: A Virological Study Addressing HSV-1 and JPCyV

by Maria Elena Marcocci, Bianka Gabriela Jackowska, Carla Prezioso, Virginia Protto, Marta De Angelis, Francesco Saverio Di Leva, Bruno Casciaro, Alfonso Carotenuto, Maria Luisa Mangoni, Anna Teresa Palamara, Valeria Pietropaolo, Giovanna De Chiara and Lucia Nencioni

Int. J. Mol. Sci. 2022, 23(13), 7194; https://doi.org/10.3390/ijms23137194 - 28 Jun 2022

Cited by 9 | Viewed by 2174

Abstract

Herpes simplex virus type-1 (HSV-1) and John Cunningham polyomavirus (JCPyV) are widely distributed DNA viruses causing mainly asymptomatic infection, but also mild to very severe diseases, especially when these viruses reach the brain. Some drugs have been developed to inhibit HSV-1 replication in host cells, but their prolonged use may induce resistance phenomena. In contrast, to date, there is no cure for JCPyV. The search for alternative drugs that can reduce viral infections without undermining the host cell is moving toward antimicrobial peptides (AMPs) of natural occurrence. These include amphibian AMPs belonging to the temporin family. Herein, we focus on temporin G (TG), showing that it strongly affects HSV-1 replication by acting either during the earliest stages of its life cycle or directly on the virion. Computational studies have revealed the ability of TG to interact with HSV-1 glycoprotein B. We also found that TG reduced JCPyV infection, probably affecting both the earliest phases of its life cycle and the viral particle, likely through an interaction with the viral capsid protein VP1. Overall, our results are promising for the development of short naturally occurring peptides as antiviral agents used to counteract diseases related to HSV-1 and JCPyV. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity)

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18 pages, 3560 KiB

Open AccessArticle

Antifungal Activity of the Frog Skin Peptide Temporin G and Its Effect on Candida albicans Virulence Factors

by Felicia Diodata D’Auria, Bruno Casciaro, Marta De Angelis, Maria Elena Marcocci, Anna Teresa Palamara, Lucia Nencioni and Maria Luisa Mangoni

Int. J. Mol. Sci. 2022, 23(11), 6345; https://doi.org/10.3390/ijms23116345 - 6 Jun 2022

Cited by 6 | Viewed by 2863

Abstract

The increasing resistance to conventional antifungal drugs is a widespread concern, and a search for new compounds, active against different species of fungi, is demanded. Antimicrobial peptides (AMPs) hold promises in this context. Here we investigated the activity of the frog skin AMP Temporin G (TG) against a panel of fungal strains, by following the Clinical and Laboratory Standards Institute protocols. TG resulted to be active against (i) Candida species and Cryptococcus neoformans, with MIC₅₀ between 4 µM and 64 µM after 24 h of incubation; (ii) dermatophytes with MIC₈₀ ranging from 4 to 32 µM, and (iii) Aspergillus strains with MIC₈₀ of 128 µM. In addition, our tests revealed that TG reduced the metabolic activity of Candida albicans cells, with moderate membrane perturbation, as proven by XTT and Sytox Green assays, respectively. Furthermore, TG was found to be effective against some C. albicans virulence factors; indeed, at 64 µM it was able to inhibit ~90% of yeast–mycelial switching, strongly prevented biofilm formation, and led to a 50% reduction of metabolic activity in mature biofilm cells, and ~30–35% eradication of mature biofilm biomass. Even though further studies are needed to deepen our knowledge of the mechanisms of TG antifungal activity, our results suggest this AMP as an attractive lead compound for treatment of fungal diseases. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity)

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12 pages, 1057 KiB

Open AccessCommunication

Garvicins AG1 and AG2: Two Novel Class IId Bacteriocins of Lactococcus garvieae Lg-Granada

by Antonio Maldonado-Barragán, Estíbaliz Alegría-Carrasco, María del Mar Blanco, Ana Isabel Vela, José Francisco Fernández-Garayzábal, Juan Miguel Rodríguez and Alicia Gibello

Int. J. Mol. Sci. 2022, 23(9), 4685; https://doi.org/10.3390/ijms23094685 - 23 Apr 2022

Cited by 7 | Viewed by 2452

Abstract

Lactococcus garvieae causes infectious diseases in animals and is considered an emerging zoonotic pathogen involved in human clinical conditions. In silico analysis of plasmid pLG50 of L. garvieae Lg-Granada, an isolate from a patient with endocarditis, revealed the presence of two gene clusters (orf46–47 and orf48–49), each one encoding a novel putative bacteriocin, i.e., garvicin AG1 (GarAG1; orf46) and garvicin AG2 (GarAG2; orf48), and their corresponding immunity proteins (orf47 and orf49). The chemically synthesised bacteriocins GarAG1 and GarAG2 presented inhibitory activity against pathogenic L. garvieae strains, with AG2 also being active against Listeria monocytogenes, Listeria ivanovii and Enterococcus faecalis. Genetic organisation, amino acid sequences and antimicrobial activities of GarAG1 and GarAG2 indicate that they belong to linear non-pediocin-like one-peptide class IId bacteriocins. Gram-positive bacteria that were sensitive to GarAG2 were also able to ferment mannose, suggesting that this bacteriocin could use the mannose phosphotransferase transport system (Man-PTS) involved in mannose uptake as a receptor in sensitive strains. Intriguingly, GarAG1 and GarAG2 were highly active against their own host, L. garvieae Lg-Granada, which could be envisaged as a new strategy to combat pathogens via their own weapons. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity)

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15 pages, 14285 KiB

Open AccessArticle

Diagnostic and Therapeutic Potential for HNP-1, HBD-1 and HBD-4 in Pregnant Women with COVID-19

by Mariarita Brancaccio, Cristina Mennitti, Mariella Calvanese, Alessandro Gentile, Roberta Musto, Giulia Gaudiello, Giulia Scamardella, Daniela Terracciano, Giulia Frisso, Raffaela Pero, Laura Sarno, Maurizio Guida and Olga Scudiero

Int. J. Mol. Sci. 2022, 23(7), 3450; https://doi.org/10.3390/ijms23073450 - 22 Mar 2022

Cited by 8 | Viewed by 2986

Abstract

Pregnancy is characterized by significant immunological changes and a cytokine profile, as well as vitamin deficiencies that can cause problems for the correct development of a fetus. Defensins are small antimicrobial peptides that are part of the innate immune system and are involved in several biological activities. Following that, this study aims to compare the levels of various cytokines and to investigate the role of defensins between pregnant women with confirmed COVID-19 infection and pregnant women without any defined risk factor. TNF-α, TGF-β, IL-2 and IL-10, β-defensins, have been evaluated by gene expression in our population. At the same time, by ELISA assay IL-6, IL-8, defensin alpha 1, defensin beta 1 and defensin beta 4 have been measured. The data obtained show that mothers affected by COVID-19 have an increase in pro-inflammatory factors (TNF-α, TGF-β, IL-2, IL-6, IL-8) compared to controls; this increase could generate a sort of “protection of the fetus” from virus attacks. Contemporarily, we have an increase in the anti-inflammatory cytokine IL-10 and an increase in AMPs, which highlights how the mother’s body is responding to the viral attack. These results allow us to hypothesize a mechanism of “trafficking” of antimicrobial peptides from the mother to the fetus that would help the fetus to protect itself from the infection in progress. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity)

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15 pages, 4007 KiB

Open AccessArticle

Influence of Substitutions in the Binding Motif of Proline-Rich Antimicrobial Peptide ARV-1502 on 70S Ribosome Binding and Antimicrobial Activity

by Alexandra Brakel, Andor Krizsan, Renke Itzenga, Carl N. Kraus, Laszlo Otvos, Jr. and Ralf Hoffmann

Int. J. Mol. Sci. 2022, 23(6), 3150; https://doi.org/10.3390/ijms23063150 - 15 Mar 2022

Cited by 6 | Viewed by 2856

Abstract

Proline-rich antimicrobial peptides (PrAMPs) are promising candidates to treat bacterial infections. The designer peptide ARV-1502 exhibits strong antimicrobial effects against Enterobacteriaceae both in vitro and in vivo. Since the inhibitory effects of ARV-1502 reported for the 70 kDa heat-shock protein DnaK do not fully explain the antimicrobial activity of its 176 substituted analogs, we further studied their effect on the bacterial 70S ribosome of Escherichia coli, a known target of PrAMPs. ARV-1502 analogues, substituted in positions 3, 4, and 8 to 12 (underlined) of the binding motif D³KPRPYLPRP¹² with aspartic acid, lysine, serine, phenylalanine or leucine, were tested in a competitive fluorescence polarization (FP) binding screening assay using 5(6)-carboxyfluorescein-labeled (Cf-) ARV-1502 and the 70S ribosome isolated from E. coli BW25113. While their effect on ribosomal protein expression was studied for green fluorescent protein (GFP) in a cell-free expression system (in vitro translation), the importance of known PrAMP transporters SbmA and MdtM was investigated using E. coli BW25113 and the corresponding knockout mutants. The dissociation constant (K_d) of 201 ± 16 nmol/L obtained for Cf-ARV-1502 suggests strong binding to the E. coli 70S ribosome. An inhibitory binding assay indicated that the binding site overlaps with those of other PrAMPs including Onc112 and pyrrhocoricin as well as the non-peptidic antibiotics erythromycin and chloramphenicol. All these drugs and drug candidates bind to the exit-tunnel of the 70S ribosome. Substitutions of the C-terminal fragment of the binding motif YLPRP reduced binding. At the same time, inhibition of GFP expression increased with net peptide charge. Interestingly, the MIC values of wild-type and ΔsbmA and ΔmdtM knockout mutants indicated that substitutions in the ribosomal binding motif altered also the bacterial uptake, which was generally improved by incorporation of hydrophobic residues. In conclusion, most substituted ARV-1502 analogs bound weaker to the 70S ribosome than ARV-1502 underlining the importance of the YLPRP binding motif. The weaker ribosomal binding correlated well with decreased antimicrobial activity in vitro. Substituted ARV-1502 analogs with a higher level of hydrophobicity or positive net charge improved the ribosome binding, inhibition of translation, and bacterial uptake. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity)

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12 pages, 2036 KiB

Open AccessArticle

Development of Bactericidal Peptides against Multidrug-Resistant Acinetobacter baumannii with Enhanced Stability and Low Toxicity

by Prakash Kishore Hazam, Chin-Cheng Cheng, Chu-Yi Hsieh, Wen-Chun Lin, Po-Hsien Hsu, Te-Li Chen, Yi-Tzu Lee and Jyh-Yih Chen

Int. J. Mol. Sci. 2022, 23(4), 2191; https://doi.org/10.3390/ijms23042191 - 16 Feb 2022

Cited by 17 | Viewed by 2604

Abstract

Pathogenic superbugs are the root cause of untreatable complex infections with limited or no treatment options. These infections are becoming more common as clinical antibiotics have lost their effectiveness over time. Therefore, the development of novel antibacterial agents is urgently needed to counter these microbes. Antimicrobial peptides (AMPs) are a viable treatment option due to their bactericidal potency against multiple microbial classes. AMPs are naturally selected physiological microbicidal agents that are found in all forms of organisms. In the present study, we developed two tilapia piscidin 2 (TP2)-based AMPs for antimicrobial application. Unlike the parent peptide, the redesigned peptides showed significant antimicrobial activity against multidrug-resistant bacterial species. These peptides also showed minimal cytotoxicity. In addition, they were significantly active in the presence of physiological salts, 50% human serum and elevated temperature. The designed peptides also showed synergistic activity when combined with clinical antibiotics. The current approach demonstrates a fruitful strategy for developing potential AMPs for antimicrobial application. Such AMPs have potential for progression to further trials and drug development investigations. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity)

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23 pages, 4189 KiB

Open AccessArticle

Design and Characterization of Myristoylated and Non-Myristoylated Peptides Effective against Candida spp. Clinical Isolates

by Francesca Bugli, Federica Massaro, Francesco Buonocore, Paolo Roberto Saraceni, Stefano Borocci, Francesca Ceccacci, Cecilia Bombelli, Maura Di Vito, Rosalba Marchitiello, Melinda Mariotti, Riccardo Torelli, Maurizio Sanguinetti and Fernando Porcelli

Int. J. Mol. Sci. 2022, 23(4), 2164; https://doi.org/10.3390/ijms23042164 - 16 Feb 2022

Cited by 11 | Viewed by 2683

Abstract

The increasing resistance of fungi to antibiotics is a severe challenge in public health, and newly effective drugs are required. Promising potential medications are lipopeptides, linear antimicrobial peptides (AMPs) conjugated to a lipid tail, usually at the N-terminus. In this paper, we investigated the in vitro and in vivo antifungal activity of three short myristoylated and non-myristoylated peptides derived from a mutant of the AMP Chionodracine. We determined their interaction with anionic and zwitterionic membrane-mimicking vesicles and their structure during this interaction. We then investigated their cytotoxic and hemolytic activity against mammalian cells. Lipidated peptides showed a broad spectrum of activity against a relevant panel of pathogen fungi belonging to Candida spp., including the multidrug-resistant C. auris. The antifungal activity was also observed vs. biofilms of C. albicans, C. tropicalis, and C. auris. Finally, a pilot efficacy study was conducted on the in vivo model consisting of Galleria mellonella larvae. Treatment with the most-promising myristoylated peptide was effective in counteracting the infection from C. auris and C. albicans and the death of the larvae. Therefore, this myristoylated peptide is a potential candidate to develop antifungal agents against human fungal pathogens. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity)

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17 pages, 2135 KiB

Open AccessArticle

Real-Time Fluorescence Microscopy on Living E. coli Sheds New Light on the Antibacterial Effects of the King Penguin β-Defensin AvBD103b

by Céline Landon, Yanyu Zhu, Mainak Mustafi, Jean-Baptiste Madinier, Dominique Lelièvre, Vincent Aucagne, Agnes F. Delmas and James C. Weisshaar

Int. J. Mol. Sci. 2022, 23(4), 2057; https://doi.org/10.3390/ijms23042057 - 12 Feb 2022

Cited by 2 | Viewed by 3592

Abstract

(1) Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics. Among AMPs, the disulfide-rich β-defensin AvBD103b, whose antibacterial activities are not inhibited by salts contrary to most other β-defensins, is particularly appealing. Information about the mechanisms of action is mandatory for the development and approval of new drugs. However, data for non-membrane-disruptive AMPs such as β-defensins are scarce, thus they still remain poorly understood. (2) We used single-cell fluorescence imaging to monitor the effects of a β-defensin (namely AvBD103b) in real time, on living E. coli, and at the physiological concentration of salts. (3) We obtained key parameters to dissect the mechanism of action. The cascade of events, inferred from our precise timing of membrane permeabilization effects, associated with the timing of bacterial growth arrest, differs significantly from the other antimicrobial compounds that we previously studied in the same physiological conditions. Moreover, the AvBD103b mechanism does not involve significant stereo-selective interaction with any chiral partner, at any step of the process. (4) The results are consistent with the suggestion that after penetrating the outer membrane and the cytoplasmic membrane, AvBD103b interacts non-specifically with a variety of polyanionic targets, leading indirectly to cell death. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity)

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17 pages, 29244 KiB

Open AccessArticle

Multi-Omics Analysis Reveals Anti-Staphylococcus aureus Activity of Actinomycin D Originating from Streptomyces parvulus

by Yuqi Lin, Li Huang, Xiaoyong Zhang, Jiajia Yang, Xiaodan Chen, Fengming Li, Jun Liu and Riming Huang

Int. J. Mol. Sci. 2021, 22(22), 12231; https://doi.org/10.3390/ijms222212231 - 12 Nov 2021

Cited by 14 | Viewed by 2956

Abstract

Staphylococcus aureus (S. aureus) is a common pathogen that causes various serious diseases, including chronic infections. Discovering new antibacterial agents is an important aspect of the pharmaceutical field because of the lack of effective antibacterial drugs. In our research, we found that one anti-S. aureus substance is actinomycin D, originating from Streptomyces parvulus (S. parvulus); then, we further focused on the anti-S. aureus ability and the omics profile of S. aureus in response to actinomycin D. The results revealed that actinomycin D had a significant inhibitory activity on S. aureus with a minimum inhibitory concentration (MIC) of 2 μg/mL and a minimum bactericidal concentration (MBC) of 64 μg/mL. Bacterial reactive oxygen species (ROS) increased 3.5-fold upon treatment with actinomycin D, as was measured with the oxidation-sensitive fluorescent probe DCFH-DA, and H₂O₂ increased 3.5 times with treatment by actinomycin D. Proteomics and metabolomics, respectively, identified differentially expressed proteins in control and treatment groups, and the co-mapped correlation network of proteomics and metabolomics annotated five major pathways that were potentially related to disrupting the energy metabolism and oxidative stress of S. aureus. All findings contributed to providing new insight into the mechanisms of the anti-S. aureus effects of actinomycin D originating from S. parvulus. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity)

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23 pages, 6487 KiB

Open AccessArticle

Novel Hybrid Peptide Cathelicidin 2 (1-13)-Thymopentin (TP5) and Its Derived Peptides with Effective Antibacterial, Antibiofilm, and Anti-Adhesion Activities

by He-Nan Guo, Yu-Cui Tong, Hui-Li Wang, Jing Zhang, Zhong-Xuan Li, Zaheer Abbas, Tian-Tian Yang, Meng-Yao Liu, Pei-Yao Chen, Zheng-Chang Hua, Xiao-Na Yan, Qiang Cheng, Marhaba Ahmat, Jun-Yong Wang, Lu-Lu Zhang, Xu-Biao Wei, Xiu-Dong Liao and Ri-Jun Zhang

Int. J. Mol. Sci. 2021, 22(21), 11681; https://doi.org/10.3390/ijms222111681 - 28 Oct 2021

Cited by 7 | Viewed by 2917

Abstract

The increasing numbers of infections caused by multidrug-resistant (MDR) pathogens highlight the urgent need for new alternatives to conventional antibiotics. Antimicrobial peptides have the potential to be promising alternatives to antibiotics because of their effective bactericidal activity and highly selective toxicity. The present study was conducted to investigate the antibacterial, antibiofilm, and anti-adhesion activities of different CTP peptides (CTP: the original hybrid peptide cathelicidin 2 (1-13)-thymopentin (TP5); CTP-NH₂: C-terminal amidated derivative of cathelicidin 2 (1-13)-TP5; CTPQ: glutamine added at the C-terminus of cathelicidin 2 (1-13)-TP5) by determining the minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), propidium iodide uptake, and analysis by scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy). The results showed that CTPs had broad-spectrum antibacterial activity against different gram-positive and gram-negative bacteria, with MICs against the tested strains varying from 2 to 64 μg/mL. CTPs at the MBC (2 × MIC 64 μg/mL) showed strong bactericidal effects on a standard methicillin-resistant Staphylococcus aureus strain ATCC 43300 after co-incubation for 6 h through disruption of the bacterial membrane. In addition, CTPs at 2 × MIC also displayed effective inhibition activity of several S. aureus strains with a 40–90% decrease in biofilm formation by killing the bacteria embedded in the biofilms. CTPs had low cytotoxicity on the intestinal porcine epithelial cell line (IPEC-J2) and could significantly decrease the rate of adhesion of S. aureus ATCC 43300 on IPEC-J2 cells. The current study proved that CTPs have effective antibacterial, antibiofilm, and anti-adhesion activities. Overall, this study contributes to our understanding of the possible antibacterial and antibiofilm mechanisms of CTPs, which might be an effective anti-MDR drug candidate. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity)

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Review

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11 pages, 986 KiB

Open AccessReview

Antimicrobial Peptide Mechanisms Studied by Whole-Cell Deuterium NMR

by Sarika Kumari and Valerie Booth

Int. J. Mol. Sci. 2022, 23(5), 2740; https://doi.org/10.3390/ijms23052740 - 1 Mar 2022

Cited by 12 | Viewed by 3204

Abstract

Much of the work probing antimicrobial peptide (AMP) mechanisms has focussed on how these molecules permeabilize lipid bilayers. However, AMPs must also traverse a variety of non-lipid cell envelope components before they reach the lipid bilayer. Additionally, there is a growing list of AMPs with non-lipid targets inside the cell. It is thus useful to extend the biophysical methods that have been traditionally applied to study AMP mechanisms in liposomes to the full bacteria, where the lipids are present along with the full complexity of the rest of the bacterium. This review focusses on what can be learned about AMP mechanisms from solid-state NMR of AMP-treated intact bacteria. It also touches on flow cytometry as a complementary method for measuring permeabilization of bacterial lipid membranes in whole bacteria. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity)

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25 pages, 933 KiB

Open AccessReview

Immunomodulatory and Allergenic Properties of Antimicrobial Peptides

by Svetlana V. Guryanova and Tatiana V. Ovchinnikova

Int. J. Mol. Sci. 2022, 23(5), 2499; https://doi.org/10.3390/ijms23052499 - 24 Feb 2022

Cited by 65 | Viewed by 5804

Abstract

With the growing problem of the emergence of antibiotic-resistant bacteria, the search for alternative ways to combat bacterial infections is extremely urgent. While analyzing the effect of antimicrobial peptides (AMPs) on immunocompetent cells, their effect on all parts of the immune system, and on humoral and cellular immunity, is revealed. AMPs have direct effects on neutrophils, monocytes, dendritic cells, T-lymphocytes, and mast cells, participating in innate immunity. They act on B-lymphocytes indirectly, enhancing the induction of antigen-specific immunity, which ultimately leads to the activation of adaptive immunity. The adjuvant activity of AMPs in relation to bacterial and viral antigens was the reason for their inclusion in vaccines and made it possible to formulate the concept of a “defensin vaccine” as an innovative basis for constructing vaccines. The immunomodulatory function of AMPs involves their influence on cells in the nearest microenvironment, recruitment and activation of other cells, supporting the response to pathogenic microorganisms and completing the inflammatory process, thus exhibiting a systemic effect. For the successful use of AMPs in medical practice, it is necessary to study their immunomodulatory activity in detail, taking into account their pleiotropy. The degree of maturity of the immune system and microenvironment can contribute to the prevention of complications and increase the effectiveness of therapy, since AMPs can suppress inflammation in some circumstances, but aggravate the response and damage of organism in others. It should also be taken into account that the real functions of one or another AMP depend on the types of total regulatory effects on the target cell, and not only on properties of an individual peptide. A wide spectrum of biological activity, including direct effects on pathogens, inactivation of bacterial toxins and influence on immunocompetent cells, has attracted the attention of researchers, however, the cytostatic activity of AMPs against normal cells, as well as their allergenic properties and low stability to host proteases, are serious limitations for the medical use of AMPs. In this connection, the tasks of searching for compounds that selectively affect the target and development of an appropriate method of application become critically important. The scope of this review is to summarize the current concepts and newest advances in research of the immunomodulatory activity of natural and synthetic AMPs, and to examine the prospects and limitations of their medical use. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity)

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