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Antimicrobial Peptides: Structure and Mechanism of Biological Activity 2.0

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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 (15 April 2023) | Viewed by 23231

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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

Related Special Issues

Antimicrobial Peptides: Structure and Mechanism of Biological Activity in International Journal of Molecular Sciences (12 articles)
Antimicrobial Peptides: Structure and Mechanism of Biological Activity 3.0 in International Journal of Molecular Sciences (4 articles)

Published Papers (11 papers)

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Research

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11 pages, 597 KiB

Open AccessArticle

Peptaibol Analogs Show Potent Antibacterial Activity against Multidrug Resistant Opportunistic Pathogens

by Chiara Dalla Torre, Filomena Sannio, Mattia Battistella, Jean-Denis Docquier and Marta De Zotti

Int. J. Mol. Sci. 2023, 24(9), 7997; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24097997 - 28 Apr 2023

Cited by 3 | Viewed by 1263

Abstract

New classes of antibacterial drugs are urgently needed to address the global issue of antibiotic resistance. In this context, peptaibols are promising membrane-active peptides since they are not involved in innate immunity and their antimicrobial activity does not involve specific cellular targets, therefore reducing the chance of bacterial resistance development. Trichogin GA IV is a nonhemolytic, natural, short-length peptaibol active against Gram-positive bacteria and resistant to proteolysis. In this work, we report on the antibacterial activity of cationic trichogin analogs. Several peptides appear non-hemolytic and strongly active against many clinically relevant bacterial species, including antibiotic-resistant clinical isolates, such as Staphylococcus aureus, Acinetobacter baumannii, and extensively drug-resistant Pseudomonas aeruginosa, against which there are only a limited number of antibiotics under development. Our results further highlight how the modification of natural peptides is a valuable strategy for obtaining improved antibacterial agents with potential therapeutic applications. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity 2.0)

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20 pages, 3161 KiB

Open AccessArticle

Nisin S, a Novel Nisin Variant Produced by Ligilactobacillus salivarius P1CEA3

by Ester Sevillano, Nuria Peña, Irene Lafuente, Luis M. Cintas, Estefanía Muñoz-Atienza, Pablo E. Hernández and Juan Borrero

Int. J. Mol. Sci. 2023, 24(7), 6813; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24076813 - 06 Apr 2023

Cited by 8 | Viewed by 2196

Abstract

Recently, the food industry and the animal farming field have been working on different strategies to reduce the use of antibiotics in animal production. The use of probiotic producers of antimicrobial peptides (bacteriocins) is considered to be a potential solution to control bacterial infections and to reduce the use of antibiotics in animal production. In this study, Ligilactobacillus salivarius P1CEA3, isolated from the gastrointestinal tract (GIT) of pigs, was selected for its antagonistic activity against Gram-positive pathogens of relevance in swine production. Whole genome sequencing (WGS) of L. salivarius P1ACE3 revealed the existence of two gene clusters involved in bacteriocin production, one with genes encoding the class II bacteriocins salivaricin B (SalB) and Abp118, and a second cluster encoding a putative nisin variant. Colony MALDI-TOF MS determinations and a targeted proteomics combined with massive peptide analysis (LC-MS/MS) of the antimicrobial peptides encoded by L. salivarius P1CEA3 confirmed the production of a 3347 Da novel nisin variant, termed nisin S, but not the production of the bacteriocins SalB and Abp118, in the supernatants of the producer strain. This is the first report of a nisin variant encoded and produced by L. salivarius, a bacterial species specially recognized for its safety and probiotic potential. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity 2.0)

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10 pages, 3062 KiB

Open AccessCommunication

Heterologous Expression and Bioactivity Determination of Monochamus alternatus Antibacterial Peptide Gene in Komagataella phaffii (Pichia pastoris)

by Xu Chu, Di Jiang, Lu Yu, Ming Li, Songqing Wu, Feiping Zhang and Xia Hu

Int. J. Mol. Sci. 2023, 24(6), 5421; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24065421 - 12 Mar 2023

Cited by 2 | Viewed by 1999

Abstract

Insects have evolved to form a variety of complex natural compounds to prevent pathogen infection in the process of a long-term attack and defense game with various pathogens in nature. Antimicrobial Peptides (AMPs) are important effector molecules of the insect immune response to the pathogen invasion involved in bacteria, fungi, viruses and nematodes. The discovery and creation of new nematicides from these natural compounds is a key path to pest control. A total of 11 AMPs from Monochamus alternatus were classified into 3 categories, including Attacin, Cecropin and Defensin. Four AMP genes were successfully expressed by Komagataella phaffii KM71. The bioassay results showed that the exogenous expressed AMPs represented antimicrobial activity against Serratia (G⁻), Bacillus thuringiensis (G⁺) and Beauveria bassiana and high nematicide activity against Bursaphelenchus xylophilus. All four purified AMPs’ protein against B. xylophilus reached LC₅₀ at 3 h (LC₅₀ = 0.19 mg·mL⁻¹ of MaltAtt-1, LC₅₀ = 0.20 mg·mL⁻¹ of MaltAtt-2 and MaltCec-2, LC₅₀ = 0.25 mg·mL⁻¹ of MaltDef-1). Furthermore, the AMPs could cause significant reduction of the thrashing frequency and egg hatching rate, and the deformation or fracture of the body wall of B. xylophilus. Therefore, this study is a foundation for further study of insect biological control and provides a theoretical basis for the research and development of new insecticidal pesticides. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity 2.0)

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12 pages, 518 KiB

Open AccessArticle

Testing Antimicrobial Properties of Selected Short Amyloids

by Przemysław Gagat, Anna Duda-Madej, Michał Ostrówka, Filip Pietluch, Alicja Seniuk, Paweł Mackiewicz and Michał Burdukiewicz

Int. J. Mol. Sci. 2023, 24(1), 804; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24010804 - 02 Jan 2023

Cited by 2 | Viewed by 1936

Abstract

Amyloids and antimicrobial peptides (AMPs) have many similarities, e.g., both kill microorganisms by destroying their membranes, form aggregates, and modulate the innate immune system. Given these similarities and the fact that the antimicrobial properties of short amyloids have not yet been investigated, we chose a group of potentially antimicrobial short amyloids to verify their impact on bacterial and eukaryotic cells. We used AmpGram, a best-performing AMP classification model, and selected ten amyloids with the highest AMP probability for our experimental research. Our results indicate that four tested amyloids: VQIVCK, VCIVYK, KCWCFT, and GGYLLG, formed aggregates under the conditions routinely used to evaluate peptide antimicrobial properties, but none of the tested amyloids exhibited antimicrobial or cytotoxic properties. Accordingly, they should be included in the negative datasets to train the next-generation AMP prediction models, based on experimentally confirmed AMP and non-AMP sequences. In the article, we also emphasize the importance of reporting non-AMPs, given that only a handful of such sequences have been officially confirmed. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity 2.0)

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18 pages, 6201 KiB

Open AccessArticle

A Novel Antimicrobial Peptide Sp-LECin with Broad-Spectrum Antimicrobial Activity and Anti-Pseudomonas aeruginosa Infection in Zebrafish

by Yan-Chao Chen, Wanlei Qiu, Weibin Zhang, Jingrong Zhang, Roushi Chen, Fangyi Chen and Ke-Jian Wang

Int. J. Mol. Sci. 2023, 24(1), 267; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24010267 - 23 Dec 2022

Cited by 8 | Viewed by 2465

Abstract

New antimicrobial agents are urgently needed to address the increasing emergence and dissemination of multidrug-resistant bacteria. In the study, a chemically synthesized truncated peptide containing 22-amino acids derived from a C-type lectin homolog SpCTL6 of Scylla paramamosain was screened and found to exhibit broad-spectrum antimicrobial activity, indicating that it is an antimicrobial peptide (AMP), named Sp-LECin. Sp-LECin possessed the basic characteristics of most cationic AMPs, such as positive charge (+4) and a relatively high hydrophobicity (45%). After treatment with Sp-LECin, the disruption of microbial membrane integrity and even leakage of cellular contents was observed by scanning electron microscopy (SEM). In addition, Sp-LECin could bind lipopolysaccharide (LPS), increase the outer and inner membrane permeability and induce reactive oxygen species (ROS) production, ultimately leading to the death of Pseudomonas aeruginosa. Furthermore, Sp-LECin exhibited potent anti-biofilm activity against P. aeruginosa during both biofilm formation and maturation. Notably, Sp-LECin had no obvious cytotoxicity and could greatly improve the survival of P. aeruginosa-infected zebrafish, by approximately 40% over the control group after 72 h of treatment. This study indicated that Sp-LECin is a promising antibacterial agent with the potential to be used against devastating global pathogen infections such as P. aeruginosa. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity 2.0)

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18 pages, 2034 KiB

Open AccessArticle

Activity and Synergy of Cu-ATCUN Antimicrobial Peptides

by Jenna M. Greve and J. A. Cowan

Int. J. Mol. Sci. 2022, 23(22), 14151; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232214151 - 16 Nov 2022

Cited by 2 | Viewed by 1559

Abstract

Antibiotic resistance demands innovative strategies and therapies. The pairs of antimicrobial peptides tested in this work show broad-spectrum synergy and are capable of interacting with diverse bacterial membranes. In most cases, the ATCUN motif enhanced the activity of peptides tested in combination. Our studies also show CP10A to be a multifaceted peptide, displaying both cell membrane and intracellular activity and acting as a chameleon, improving the activity of other peptides as needed. The results of the synergy experiments demonstrate the importance of varied modes of action and how these changes can affect the ability to combat pathogens, while also illustrating the value of the metal-binding domain in enhancing the activity of antimicrobial peptides in combination. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity 2.0)

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15 pages, 5363 KiB

Open AccessArticle

A Non-Canonical Teleost NK-Lysin: Antimicrobial Activity via Multiple Mechanisms

by Hang Xu, Zihao Yuan and Li Sun

Int. J. Mol. Sci. 2022, 23(21), 12722; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232112722 - 22 Oct 2022

Cited by 4 | Viewed by 1407

Abstract

NK-lysin (NKL) is a family of antimicrobial proteins with an important role in innate and adaptive immunity. In this study, a non-canonical NK-lysin (NKLnc) was identified in the Japanese flounder (Paralichthys olivaceus), which shares low sequence identities (15.8–20.6%) with previously reported fish NKLs and was phylogenetically separated from the canonical NKLs in teleost. NKLnc expression was upregulated in flounder tissues during bacterial infection, and interference with NKLnc expression impaired the ability of flounder cells to eliminate invading bacteria. When expressed in Escherichia coli, NKLnc was detrimental to the host cells. P35, a peptide derived from the saposin B domain (SapB) of NKLnc, bound major bacterial surface molecules and killed both Gram-negative and Gram-positive bacteria by inflicting damage to bacterial cell structure and genomic DNA. The bactericidal activity, but not the bacteria-binding capacity, of P35 required the structural integrity of the alpha 2/3 helices in SapB. Furthermore, P35 induced the migration of flounder peripheral blood leukocytes, inhibited bacterial dissemination in fish tissues, and facilitated fish survival after bacterial challenge. Together our study reveals that NKLnc plays an important part in flounder immune defense, and that NKLnc peptide exerts an antimicrobial effect via multiple mechanisms by targeting both bacteria and fish cells. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity 2.0)

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18 pages, 2860 KiB

Open AccessArticle

Characterization of Recombinant Antimicrobial Peptide BMGlv2 Heterologously Expressed in Trichoderma reesei

by Qingping Liang, Linyuan Cao, Changliang Zhu, Qing Kong, Han Sun, Fang Zhang, Haijin Mou and Zhemin Liu

Int. J. Mol. Sci. 2022, 23(18), 10291; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810291 - 07 Sep 2022

Cited by 3 | Viewed by 1578

Abstract

Antimicrobial peptides (AMPs) serve as alternative candidates for antibiotics and have attracted the attention of a wide range of industries for various purposes, including the prevention and treatment of piglet diarrhea in the swine industry. Escherichia coli, Salmonella, and Clostridium perfringens are the most common pathogens causing piglet diarrhea. In this study, the antimicrobial peptide gloverin2 (BMGlv2), derived from Bombyx mandarina, was explored to determine the efficient prevention effect on bacterial piglet diarrhea. BMGlv2 was heterologously expressed in Trichoderma reesei Tu6, and its antimicrobial properties against the three bacteria were characterized. The results showed that the minimum inhibitory concentrations of the peptide against E. coli ATCC 25922, S. derby ATCC 13076, and C. perfringens CVCC 2032 were 43.75, 43.75, and 21.86 μg/mL, respectively. The antimicrobial activity of BMGlv2 was not severely affected by high temperature, salt ions, and digestive enzymes. It had low hemolytic activity against rabbit red blood cells, indicating its safety for use as a feed additive. Furthermore, the measurements of the leakage of bacterial cell contents and scanning electron microscopy of C. perfringens CVCC 2032 indicated that BMGlv2 exerted antimicrobial activity by destroying the cell membrane. Overall, this study showed the heterologous expression of the antimicrobial peptide BMGlv2 in T. reesei and verified its antimicrobial properties against three common pathogenic bacteria associated with piglet diarrhea, which can provide a reference for the applications of AMPs as an alternative product in industrial agriculture. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity 2.0)

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Review

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15 pages, 5763 KiB

Open AccessReview

Unlocking the Potential of the Antimicrobial Peptide Gomesin: From Discovery and Structure–Activity Relationships to Therapeutic Applications

by Xiaorong Liu, Sónia T. Henriques, David J. Craik and Lai Yue Chan

Int. J. Mol. Sci. 2023, 24(6), 5893; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24065893 - 20 Mar 2023

Viewed by 2148

Abstract

Gomesin is a cationic antimicrobial peptide which is isolated from the haemocytes of the Brazilian tarantula Acanthoscurria gomesiana and can be produced chemically by Fmoc solid-phase peptide synthesis. Gomesin exhibits a range of biological activities, as demonstrated by its toxicity against therapeutically relevant pathogens such as Gram-positive or Gram-negative bacteria, fungi, cancer cells, and parasites. In recent years, a cyclic version of gomesin has been used for drug design and development as it is more stable than native gomesin in human serum and can penetrate and enter cancer cells. It can therefore interact with intracellular targets and has the potential to be developed as a drug lead for to treat cancer, infectious diseases, and other human diseases. This review provides a perspective on the discovery, structure–activity relationships, mechanism of action, biological activity, and potential clinical applications of gomesin. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity 2.0)

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32 pages, 2269 KiB

Open AccessReview

Temporins: Multifunctional Peptides from Frog Skin

by Luca Domenico D'Andrea and Alessandra Romanelli

Int. J. Mol. Sci. 2023, 24(6), 5426; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24065426 - 12 Mar 2023

Cited by 10 | Viewed by 2477

Abstract

Temporins are short peptides secreted by frogs from all over the world. They exert antimicrobial activity, mainly against Gram-positive bacteria, including resistant pathogens; recent studies highlight other possible applications of these peptides as anticancer or antiviral agents. This review is meant to describe the main features of temporins produced by different ranid genera. Due to the abundance of published papers, we focus on the most widely investigated peptides. We report studies on their mechanism of action and three-dimensional structure in model systems mimicking bacterial membranes or in the presence of cells. The design and the antimicrobial activity of peptide analogues is also described, with the aim of highlighting elements that are crucial to improve the bioactivity of peptides while reducing their toxicity. Finally, a short section is dedicated to the studies aimed at applying these peptides as drugs, to produce new antimicrobial materials or in other technological uses. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity 2.0)

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17 pages, 935 KiB

Open AccessReview

Biologically Active Peptides from Venoms: Applications in Antibiotic Resistance, Cancer, and Beyond

by Lucía Ageitos, Marcelo D. T. Torres and Cesar de la Fuente-Nunez

Int. J. Mol. Sci. 2022, 23(23), 15437; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232315437 - 06 Dec 2022

Cited by 6 | Viewed by 2879

Abstract

Peptides are potential therapeutic alternatives against global diseases, such as antimicrobial-resistant infections and cancer. Venoms are a rich source of bioactive peptides that have evolved over time to act on specific targets of the prey. Peptides are one of the main components responsible for the biological activity and toxicity of venoms. South American organisms such as scorpions, snakes, and spiders are important producers of a myriad of peptides with different biological activities. In this review, we report the main venom-derived peptide families produced from South American organisms and their corresponding activities and biological targets. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity 2.0)

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