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Antibiotics
Special Issues
Therapeutic Use of Antimicrobial Peptides: Joys and Sorrows
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Therapeutic Use of Antimicrobial Peptides: Joys and Sorrows

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antimicrobial Peptides".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 24863

Special Issue Editors

Prof. Dr. Giovanna Batoni

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Guest Editor
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
Interests: antimicrobial peptides; biofilm infections; unconventional antimicrobials; wound infections; pulmonary infections; host response to infections; Pseudomonas aeruginosa; Mycobacterium tuberculosis
Special Issues, Collections and Topics in MDPI journals
Dr. Giuseppantonio Maisetta

E-Mail Website
Co-Guest Editor
Department of Translational Research and New technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
Interests: bacteria; pathogens; biofilm; bacterial virulence; persisters; antimicrobial peptides; antibiotics
Special Issues, Collections and Topics in MDPI journals
Dr. Semih Esin

E-Mail Website
Co-Guest Editor
Department of Translational Research on New Technologies in Medicine and Surgery, Università di Pisa, Pisa, Italy
Interests: immune system; mycobacterial infections; virulence factors and Mycobacterium tuberculosis; natural molecules with antimicrobial and /or immunomodulatory activity; infections sustained by microbial biofilms and the host's immune response
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antimicrobial peptides (AMPs) and their synthetic derivatives are considered promising leads to develop novel antibiotics. In addition to their generally fast, strong, and wide-spectrum antimicrobial activity against multidrug-resistant (MDR) strains, these molecules are often also equipped with an array of favorable biological activities that include the ability to modulate immune responses, recruit immune cells, neutralize bacterial (endo)toxins, and promote angiogenesis and tissue regeneration. Recently, interest in AMPs as new anti-infective drugs has extended to their possible use against microbial biofilms as they exhibit a number of properties that may be optimal for interfering with the biofilm mode of growth. Despite the numerous attractive features of AMPs as new antimicrobials, a relatively small number of them has entered clinical trials, and an even smaller number has reached the market. Possible drawbacks, such as susceptibility to protease digestion, low cytocompatibility, high production costs, and potential development of resistance, have contributed to a general skepticism towards the real possibility to translate AMPs into clinically useful molecules, especially for the treatment of systemic infections. The aim of this Special Issue is to gather a collection of papers addressing the therapeutic potential of AMPs, enlightening the positive features but also the possible drawbacks deriving from their use as new antibiotics. Special interest will be devoted to studies addressing the effectiveness of peptide treatments against human infections, taking into account the environment in which the peptide will be used clinically. These include ex vivo and in vitro models that reproduce, as much as possible, the conditions found in the human host regarding the presence of serum, salts, other biological components or the normal flora that may inhibit peptides’ activity in vivo. It is hoped that this Special Issue will help in identifying the “minimum” features that an AMP must have to be worth directing it towards animal studies or clinical trials.

Prof. Giovanna Batoni
Dr. Giuseppantonio Maisetta
Dr. Semih Esin
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antimicrobial peptides
  • host defense peptides
  • in vitro models, ex vivo models
  • in vivo models
  • biofilms
  • host mimicking conditions

Published Papers (6 papers)

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Research

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16 pages, 1915 KiB  
Article
The Influence of Cellulose-Type Formulants on Anti-Candida Activity of the Tyrocidines
by Yasamin Masoudi, Wilma van Rensburg, Bernice Barnard-Jenkins and Marina Rautenbach
Antibiotics 2021, 10(5), 597; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10050597 - 18 May 2021
Cited by 3 | Viewed by 2106
Abstract
Candida species are highly adaptable to environmental changes with their phenotypic flexibility allowing for the evasion of most host defence mechanisms. Moreover, increasing resistance of human pathogenic Candida strains has been reported against all four classes of available antifungal drugs, which highlights the [...] Read more.
Candida species are highly adaptable to environmental changes with their phenotypic flexibility allowing for the evasion of most host defence mechanisms. Moreover, increasing resistance of human pathogenic Candida strains has been reported against all four classes of available antifungal drugs, which highlights the need for combinational therapies. Tyrocidines are cyclic antimicrobial peptides that have shown synergistic activity with antifungal drugs such as caspofungin and amphotericin B. However, these cyclodecapeptides have haemolytic activity and cytotoxicity, but they have been used for decades in the clinic for topical applications. The tyrocidines tend to form higher-order structures in aqueous solutions and excessive aggregation can result in variable or diminished activity. Previous studies have shown that the tyrocidines prefer ordered association to celluloses. Therefore, a formulation with soluble cellulose was used to control the oligomer stability and size, thereby increasing the activity against Candida spp. Of the formulants tested, it was found that commercial hydroxy-propyl-methyl cellulose, E10M, yielded the best results with increased stability, increased anti-Candida activity, and improved selectivity. This formulation holds promise in topical applications against Candida spp. infections. Full article
(This article belongs to the Special Issue Therapeutic Use of Antimicrobial Peptides: Joys and Sorrows)
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12 pages, 1535 KiB  
Article
Pigs Overexpressing Porcine β-Defensin 2 Display Increased Resilience to Glaesserella parasuis Infection
by Jing Huang, Xiaoyu Yang, Antian Wang, Chao Huang, Hao Tang, Qiuhong Zhang, Qiong Fang, Zuming Yu, Xiao Liu, Qi Huang, Rui Zhou and Lu Li
Antibiotics 2020, 9(12), 903; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9120903 - 14 Dec 2020
Cited by 10 | Viewed by 3244
Abstract
As the causative agent of Glässer’s disease, Glaesserella (Haemophilus) parasuis has led to serious economic losses to the swine industry worldwide. Due to the low cross-protection of vaccines and increasing antimicrobial resistance of G. parasuis, it is important to develop alternative approaches [...] Read more.
As the causative agent of Glässer’s disease, Glaesserella (Haemophilus) parasuis has led to serious economic losses to the swine industry worldwide. Due to the low cross-protection of vaccines and increasing antimicrobial resistance of G. parasuis, it is important to develop alternative approaches to prevent G. parasuis infection. Defensins are host defense peptides that have been suggested to be promising substitutes for antibiotics in animal production, while porcine β-defensin 2 (PBD-2) is a potent antimicrobial peptide discovered in pigs. Our previous study generated transgenic (TG) pigs overexpressing PBD-2, which displayed enhanced resistance to Actinobacillus pleuropneumoniae. In this study, the antibacterial activities of PBD-2 against G. parasuis are determined in vitro and in the TG pig model. The concentration-dependent bactericidal activity of synthetic PBD-2 against G. parasuis was measured by bacterial counting. Moreover, after being infected with G. parasuis via a cohabitation challenge model, TG pigs overexpressing PBD-2 displayed significantly milder clinical signs and less severe gross pathological changes than their wild-type (WT) littermates. The TG pigs also exhibited alleviated lung and brain lesions, while bacterial loads in the lung and brain tissues of the TG pigs were significantly lower than those of the WT pigs. Additionally, lung and brain homogenates from TG pigs possessed enhanced antibacterial activity against G. parasuis when compared with those from the WT pigs. Altogether, these proved that overexpression of PBD-2 could also endow pigs with increased resilience to G. parasuis infection, which further confirmed the potential of using the PBD-2 coding gene to develop disease-resistant pigs and provided a novel strategy to combat G. parasuis as well. Full article
(This article belongs to the Special Issue Therapeutic Use of Antimicrobial Peptides: Joys and Sorrows)
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14 pages, 1437 KiB  
Article
The Anti-Microbial Peptide (Lin-SB056-1)2-K Reduces Pro-Inflammatory Cytokine Release through Interaction with Pseudomonas aeruginosa Lipopolysaccharide
by Lucia Grassi, Arianna Pompilio, Esingül Kaya, Andrea C. Rinaldi, Enrico Sanjust, Giuseppantonio Maisetta, Aurélie Crabbé, Giovanni Di Bonaventura, Giovanna Batoni and Semih Esin
Antibiotics 2020, 9(9), 585; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9090585 - 08 Sep 2020
Cited by 6 | Viewed by 2484
Abstract
The ability of many anti-microbial peptides (AMPs) to modulate the host immune response has highlighted their possible therapeutic use to reduce uncontrolled inflammation during chronic infections. In the present study, we examined the anti-inflammatory potential of the semi-synthetic peptide lin-SB056-1 and its dendrimeric [...] Read more.
The ability of many anti-microbial peptides (AMPs) to modulate the host immune response has highlighted their possible therapeutic use to reduce uncontrolled inflammation during chronic infections. In the present study, we examined the anti-inflammatory potential of the semi-synthetic peptide lin-SB056-1 and its dendrimeric derivative (lin-SB056-1)2-K, which were previously found to have anti-microbial activity against Pseudomonas aeruginosa in in vivo-like models mimicking the challenging environment of chronically infected lungs (i.e., artificial sputum medium and 3-D lung mucosa model). The dendrimeric derivative exerted a stronger anti-inflammatory activity than its monomeric counterpart towards lung epithelial- and macrophage-cell lines stimulated with P. aeruginosa lipopolysaccharide (LPS), based on a marked decrease (up to 80%) in the LPS-induced production of different pro-inflammatory cytokines (i.e., IL-1β, IL-6 and IL-8). Accordingly, (lin-SB056-1)2-K exhibited a stronger LPS-binding affinity than its monomeric counterpart, thereby suggesting a role of peptide/LPS neutralizing interactions in the observed anti-inflammatory effect. Along with the anti-bacterial and anti-biofilm properties, the anti-inflammatory activity of (lin-SB056-1)2-K broadens its therapeutic potential in the context of chronic (biofilm-associated) infections. Full article
(This article belongs to the Special Issue Therapeutic Use of Antimicrobial Peptides: Joys and Sorrows)
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Review

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32 pages, 719 KiB  
Review
The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent
by Kylen E. Ridyard and Joerg Overhage
Antibiotics 2021, 10(6), 650; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060650 - 29 May 2021
Cited by 81 | Viewed by 8507
Abstract
The rise in antimicrobial resistant bacteria threatens the current methods utilized to treat bacterial infections. The development of novel therapeutic agents is crucial in avoiding a post-antibiotic era and the associated deaths from antibiotic resistant pathogens. The human antimicrobial peptide LL-37 has been [...] Read more.
The rise in antimicrobial resistant bacteria threatens the current methods utilized to treat bacterial infections. The development of novel therapeutic agents is crucial in avoiding a post-antibiotic era and the associated deaths from antibiotic resistant pathogens. The human antimicrobial peptide LL-37 has been considered as a potential alternative to conventional antibiotics as it displays broad spectrum antibacterial and anti-biofilm activities as well as immunomodulatory functions. While LL-37 has shown promising results, it has yet to receive regulatory approval as a peptide antibiotic. Despite the strong antimicrobial properties, LL-37 has several limitations including high cost, lower activity in physiological environments, susceptibility to proteolytic degradation, and high toxicity to human cells. This review will discuss the challenges associated with making LL-37 into a viable antibiotic treatment option, with a focus on antimicrobial resistance and cross-resistance as well as adaptive responses to sub-inhibitory concentrations of the peptide. The possible methods to overcome these challenges, including immobilization techniques, LL-37 delivery systems, the development of LL-37 derivatives, and synergistic combinations will also be considered. Herein, we describe how combination therapy and structural modifications to the sequence, helicity, hydrophobicity, charge, and configuration of LL-37 could optimize the antimicrobial and anti-biofilm activities of LL-37 for future clinical use. Full article
(This article belongs to the Special Issue Therapeutic Use of Antimicrobial Peptides: Joys and Sorrows)
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12 pages, 1212 KiB  
Review
Attacins: A Promising Class of Insect Antimicrobial Peptides
by Francesco Buonocore, Anna Maria Fausto, Giulia Della Pelle, Tomislav Roncevic, Marco Gerdol and Simona Picchietti
Antibiotics 2021, 10(2), 212; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10020212 - 20 Feb 2021
Cited by 43 | Viewed by 5036
Abstract
Insects produce a large repertoire of antimicrobial peptides (AMPs) as the first line of defense against bacteria, viruses, fungi or parasites. These peptides are produced from a large precursor that contains a signal domain, which is cleaved in vivo to produce the mature [...] Read more.
Insects produce a large repertoire of antimicrobial peptides (AMPs) as the first line of defense against bacteria, viruses, fungi or parasites. These peptides are produced from a large precursor that contains a signal domain, which is cleaved in vivo to produce the mature protein with antimicrobial activity. At present, AMPs from insects include several families which can be classified as cecropins, ponericins, defensins, lebocins, drosocin, Metchnikowin, gloverins, diptericins and attacins according to their structure and/or function. This short review is focused on attacins, a class of glycine-rich peptides/proteins that have been first discovered in the cecropia moth (Hyalophora cecropia). They are a rather heterogeneous group of immunity-related proteins that exhibit an antimicrobial effect mainly against Gram-negative bacteria. Here, we discuss different attacin and attacin-like AMPs that have been discovered so far and analyze their structure and phylogeny. Special focus is given to the physiological importance and mechanism of action of attacins against microbial pathogens together with their potential pharmacological applications, emphasizing their roles as antimicrobials. Full article
(This article belongs to the Special Issue Therapeutic Use of Antimicrobial Peptides: Joys and Sorrows)
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Other

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8 pages, 393 KiB  
Brief Report
The Short Lipopeptides (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 Protect HaCaT Keratinocytes from Bacterial Damage Caused by Staphylococcus aureus Infection in a Co-Culture Model
by Kirsten Reddersen, Katarzyna E. Greber, Izabela Korona-Glowniak and Cornelia Wiegand
Antibiotics 2020, 9(12), 879; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9120879 - 08 Dec 2020
Cited by 2 | Viewed by 2076
Abstract
The search for new antimicrobial strategies is of major importance since there is a growing resistance of both bacteria and fungi to existing antimicrobials. Lipopeptides are promising and potent antimicrobial compounds. For translation into clinically useful molecules, effectiveness of peptide treatment against human [...] Read more.
The search for new antimicrobial strategies is of major importance since there is a growing resistance of both bacteria and fungi to existing antimicrobials. Lipopeptides are promising and potent antimicrobial compounds. For translation into clinically useful molecules, effectiveness of peptide treatment against human infections must be proved in complex in vitro wound models. The aim of this study was to examine if the synthesized short lipopeptides (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 can protect HaCaT keratinocytes from bacterial damage caused by Staphylococcus aureus infection in a coculture model. After 1 h, 24 h, and 48 h incubation, cellular ATP level and release of the cytotoxicity marker LDH as well as the proinflammatory cytokines interleukin-6 and interleukin-1α were measured. Infection of the keratinocytes resulted in strong bacterial damage of HaCaT cells along with low cellular ATP levels and high release of LDH, IL-6, and IL-1α after 24 h and 48 h. Incubation of the infected human keratinocytes with (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 resulted in protection of the keratinocytes from bacterial damage caused by Staphylococcus aureus infection with ATP, LDH, IL-6, and IL-1α levels comparable to the untreated control. Hence, both synthesized lipopeptides are promising candidates with high therapeutic potential in dermatology for the treatment of topical infections. Full article
(This article belongs to the Special Issue Therapeutic Use of Antimicrobial Peptides: Joys and Sorrows)
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