Antibiotics

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17 pages, 2454 KiB

Open AccessArticle

Fragments of a Wheat Hevein-Like Antimicrobial Peptide Augment the Inhibitory Effect of a Triazole Fungicide on Spore Germination of Fusarium oxysporum and Alternaria solani

by Larisa Shcherbakova, Tatyana Odintsova, Tatyana Pasechnik, Lenara Arslanova, Tatyana Smetanina, Maxim Kartashov, Marina Slezina and Vitaly Dzhavakhiya

Antibiotics 2020, 9(12), 870; https://doi.org/10.3390/antibiotics9120870 - 4 Dec 2020

Cited by 8 | Viewed by 2760

Abstract

There are increasing environmental risks associated with extensive use of fungicides for crop protection. Hence, the use of new approaches using natural plant defense mechanisms, including application of plant antimicrobial peptides (AMPs), is of great interest. Recently, we studied the structural–function relationships between [...] Read more.

There are increasing environmental risks associated with extensive use of fungicides for crop protection. Hence, the use of new approaches using natural plant defense mechanisms, including application of plant antimicrobial peptides (AMPs), is of great interest. Recently, we studied the structural–function relationships between antifungal activity and five hevein-like AMPs from the WAMP (wheat AMP) family of Triticum kiharae Dorof. et Migush. We first discovered that short peptides derived from the central, N-, and C-terminal regions of one of the WAMPs (WAMP-2) were able to augment the inhibitory effect of Folicur^® EC 250, a triazole fungicide, on spore germination of the wheat pathogenic fungi, including Fusarium spp. and Alternaria alternata. In this research, we explored the ability of chemically synthesized WAMP-2-derived peptides for enhancing the sensitivity of two other Fusarium and Alternaria species, F. oxysporum and A. solani, causing wilt and early blight of tomato, respectively, to Folicur^®. The synthesized WAMP-2-derived peptides synergistically interacted with the fungicide and significantly increased its efficacy, inhibiting conidial germination at much lower Folicur^® concentrations than required for the same efficiency using the fungicide alone. The experiments on co-applications of some of WAMP-2-fragments and the fungicide on tomato leaves and seedlings, which confirmed the results obtained in vitro, are described. Full article

(This article belongs to the Special Issue Synthesis and Utility of Antimicrobial Peptides)

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20 pages, 1853 KiB

Open AccessArticle

Putative Antimicrobial Peptides of the Posterior Salivary Glands from the Cephalopod Octopus vulgaris Revealed by Exploring a Composite Protein Database

by Daniela Almeida, Dany Domínguez-Pérez, Ana Matos, Guillermin Agüero-Chapin, Hugo Osório, Vitor Vasconcelos, Alexandre Campos and Agostinho Antunes

Antibiotics 2020, 9(11), 757; https://doi.org/10.3390/antibiotics9110757 - 30 Oct 2020

Cited by 10 | Viewed by 4380

Abstract

Cephalopods, successful predators, can use a mixture of substances to subdue their prey, becoming interesting sources of bioactive compounds. In addition to neurotoxins and enzymes, the presence of antimicrobial compounds has been reported. Recently, the transcriptome and the whole proteome of the Octopus [...] Read more.

Cephalopods, successful predators, can use a mixture of substances to subdue their prey, becoming interesting sources of bioactive compounds. In addition to neurotoxins and enzymes, the presence of antimicrobial compounds has been reported. Recently, the transcriptome and the whole proteome of the Octopus vulgaris salivary apparatus were released, but the role of some compounds—e.g., histones, antimicrobial peptides (AMPs), and toxins—remains unclear. Herein, we profiled the proteome of the posterior salivary glands (PSGs) of O. vulgaris using two sample preparation protocols combined with a shotgun-proteomics approach. Protein identification was performed against a composite database comprising data from the UniProtKB, all transcriptomes available from the cephalopods’ PSGs, and a comprehensive non-redundant AMPs database. Out of the 10,075 proteins clustered in 1868 protein groups, 90 clusters corresponded to venom protein toxin families. Additionally, we detected putative AMPs clustered with histones previously found as abundant proteins in the saliva of O. vulgaris. Some of these histones, such as H2A and H2B, are involved in systemic inflammatory responses and their antimicrobial effects have been demonstrated. These results not only confirm the production of enzymes and toxins by the O. vulgaris PSGs but also suggest their involvement in the first line of defense against microbes. Full article

(This article belongs to the Special Issue Synthesis and Utility of Antimicrobial Peptides)

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13 pages, 2601 KiB

Open AccessArticle

Identification of New Antimicrobial Peptides from Mediterranean Medical Plant Charybdis pancration (Steinh.) Speta

by Vincenzo Cunsolo, Rosario Schicchi, Marco Chiaramonte, Luigi Inguglia, Vincenzo Arizza, Maria Grazia Cusimano, Domenico Schillaci, Antonella Di Francesco, Rosaria Saletti, Fabrizio Lo Celso, Giampaolo Barone and Maria Vitale

Antibiotics 2020, 9(11), 747; https://doi.org/10.3390/antibiotics9110747 - 28 Oct 2020

Cited by 11 | Viewed by 3068

Abstract

The present work was designed to identify and characterize novel antimicrobial peptides (AMPs) from Charybdis pancration (Steinh.) Speta, previously named Urginea maritima, is a Mediterranean plant, well-known for its biological properties in traditional medicine. Polypeptide-enriched extracts from different parts of the plant [...] Read more.

The present work was designed to identify and characterize novel antimicrobial peptides (AMPs) from Charybdis pancration (Steinh.) Speta, previously named Urginea maritima, is a Mediterranean plant, well-known for its biological properties in traditional medicine. Polypeptide-enriched extracts from different parts of the plant (roots, leaves and bulb), never studied before, were tested against two relevant pathogens, Staphylococcus aureus and Pseudomonas aeruginosa. With the aim of identifying novel natural AMPs, peptide fraction displaying antimicrobial activity (the bulb) that showed minimum inhibitory concentration (MICs) equal to 30 µg/mL against the above mentioned strains, was analysed by high-resolution mass spectrometry and database search. Seventeen peptides, related to seven proteins present in the investigated database, were described. Furthermore, we focused on three peptides, which due to their net positive charge, have a better chance to be AMPs and they were investigated by molecular modelling approaches, in order to shed light on the solution properties of their equilibrium structures. Some of new detected peptides could represent a good platform for the development of new antimicrobials in the fight against antibiotic resistance phenomenon. Full article

(This article belongs to the Special Issue Synthesis and Utility of Antimicrobial Peptides)

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19 pages, 1975 KiB

Open AccessArticle

Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates

by Yu Zai, Yuan Ying, Zhuming Ye, Mei Zhou, Chengbang Ma, Zhanzhong Shi, Xiaoling Chen, Xinping Xi, Tianbao Chen and Lei Wang

Antibiotics 2020, 9(9), 627; https://doi.org/10.3390/antibiotics9090627 - 21 Sep 2020

Cited by 18 | Viewed by 3689

Abstract

DMPC-10A (ALWKKLLKK-Cha-NH₂) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid [...] Read more.

DMPC-10A (ALWKKLLKK-Cha-NH₂) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid enantiomer (DMPC-10B) was designed by substituting all L-Lys and L-Leu with their respective D-form amino acid residues, while the Ala¹ and Trp³ remained unchanged. The D-amino acid enantiomer exhibited similar antimicrobial potency to the parent peptide but exerted lower cytotoxicity and hemolytic activity. Meanwhile, DMPC-10B exhibited remarkable resistance to hydrolysis by trypsin and chymotrypsin. In addition to these advantages, DMPC-10B exhibited an outstanding antibacterial effect against Methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae using the Galleria mellonella larva model and displayed synergistic activities with gentamicin against carbapenem-resistant K. pneumoniae strains. This indicates that DMPC-10B would be a promising alternative for treating antibiotic-resistant pathogens. Full article

(This article belongs to the Special Issue Synthesis and Utility of Antimicrobial Peptides)

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13 pages, 950 KiB

Open AccessArticle

Analogues of a Cyclic Antimicrobial Peptide with a Flexible Linker Show Promising Activity against Pseudomonas aeruginosa and Staphylococcus aureus

by Thomas T. Thomsen, Helen C. Mendel, Wafaa Al-Mansour, Alberto Oddo, Anders Løbner-Olesen and Paul R. Hansen

Antibiotics 2020, 9(7), 366; https://doi.org/10.3390/antibiotics9070366 - 30 Jun 2020

Cited by 13 | Viewed by 4187

Abstract

The emergence of multi-drug resistant bacteria is becoming a major health concern. New strategies to combat especially Gram-negative pathogens are urgently needed. Antimicrobial peptides (AMPs) found in all multicellular organisms act as a first line of defense in immunity. In recent years, AMPs [...] Read more.

The emergence of multi-drug resistant bacteria is becoming a major health concern. New strategies to combat especially Gram-negative pathogens are urgently needed. Antimicrobial peptides (AMPs) found in all multicellular organisms act as a first line of defense in immunity. In recent years, AMPs have attracted increasing attention as potential antibiotics. Naturally occurring antimicrobial cyclic lipopeptides include colistin and daptomycin, both of which contain a flexible linker. We previously reported a cyclic AMP BSI-9 cyclo(Lys-Nal-Lys-Lys-Bip-O₂Oc-Nal-Lys-Asn) containing a flexible linker, with a broad spectrum of activity against bacterial strains and low hemolytic activity. In this study, improvement of the antimicrobial activity of BSI-9, against the European Committee on Antimicrobial Susceptibility Testing (EUCAST) strains of S. aureus, E. coli, A. baumannii, and P. aeruginosa was examined. This led to synthesis of eighteen peptide analogues of BSI-9, produced in four individual stages, with a different focus in each stage; cyclization point, hydrophobicity, cationic side-chain length, and combinations of the last two. Specifically the modified compound 11, exhibited improved activity against Staphylococcus aureus and Pseudomonas aeruginosa with MIC of 4 µg/mL and 8 µg/mL, respectively, compared to the original BSI-9, which had an MIC of 16–32 µg/mL. Full article

(This article belongs to the Special Issue Synthesis and Utility of Antimicrobial Peptides)

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Review

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41 pages, 5241 KiB

Open AccessReview

Design, Screening, and Testing of Non-Rational Peptide Libraries with Antimicrobial Activity: In Silico and Experimental Approaches

by Paola Ruiz Puentes, María C. Henao, Carlos E. Torres, Saúl C. Gómez, Laura A. Gómez, Juan C. Burgos, Pablo Arbeláez, Johann F. Osma, Carolina Muñoz-Camargo, Luis H. Reyes and Juan C. Cruz

Antibiotics 2020, 9(12), 854; https://doi.org/10.3390/antibiotics9120854 - 30 Nov 2020

Cited by 19 | Viewed by 8307

Abstract

One of the challenges of modern biotechnology is to find new routes to mitigate the resistance to conventional antibiotics. Antimicrobial peptides (AMPs) are an alternative type of biomolecules, naturally present in a wide variety of organisms, with the capacity to overcome the current [...] Read more.

One of the challenges of modern biotechnology is to find new routes to mitigate the resistance to conventional antibiotics. Antimicrobial peptides (AMPs) are an alternative type of biomolecules, naturally present in a wide variety of organisms, with the capacity to overcome the current microorganism resistance threat. Here, we reviewed our recent efforts to develop a new library of non-rationally produced AMPs that relies on bacterial genome inherent diversity and compared it with rationally designed libraries. Our approach is based on a four-stage workflow process that incorporates the interplay of recent developments in four major emerging technologies: artificial intelligence, molecular dynamics, surface-display in microorganisms, and microfluidics. Implementing this framework is challenging because to obtain reliable results, the in silico algorithms to search for candidate AMPs need to overcome issues of the state-of-the-art approaches that limit the possibilities for multi-space data distribution analyses in extremely large databases. We expect to tackle this challenge by using a recently developed classification algorithm based on deep learning models that rely on convolutional layers and gated recurrent units. This will be complemented by carefully tailored molecular dynamics simulations to elucidate specific interactions with lipid bilayers. Candidate AMPs will be recombinantly-expressed on the surface of microorganisms for further screening via different droplet-based microfluidic-based strategies to identify AMPs with the desired lytic abilities. We believe that the proposed approach opens opportunities for searching and screening bioactive peptides for other applications. Full article

(This article belongs to the Special Issue Synthesis and Utility of Antimicrobial Peptides)

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15 pages, 653 KiB

Open AccessReview

Synergies with and Resistance to Membrane-Active Peptides

by Adam Kmeck, Robert J. Tancer, Cristina R. Ventura and Gregory R. Wiedman

Antibiotics 2020, 9(9), 620; https://doi.org/10.3390/antibiotics9090620 - 19 Sep 2020

Cited by 13 | Viewed by 4759

Abstract

Membrane-active peptides (MAPs) have long been thought of as the key to defeating antimicrobial-resistant microorganisms. Such peptides, however, may not be sufficient alone. In this review, we seek to highlight some of the common pathways for resistance, as well as some avenues for [...] Read more.

Membrane-active peptides (MAPs) have long been thought of as the key to defeating antimicrobial-resistant microorganisms. Such peptides, however, may not be sufficient alone. In this review, we seek to highlight some of the common pathways for resistance, as well as some avenues for potential synergy. This discussion takes place considering resistance, and/or synergy in the extracellular space, at the membrane, and during interaction, and/or removal. Overall, this review shows that researchers require improved definitions of resistance and a more thorough understanding of MAP-resistance mechanisms. The solution to combating resistance may ultimately come from an understanding of how to harness the power of synergistic drug combinations. Full article

(This article belongs to the Special Issue Synthesis and Utility of Antimicrobial Peptides)

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26 pages, 2653 KiB

Open AccessReview

Strategies for Optimizing the Production of Proteins and Peptides with Multiple Disulfide Bonds

by Yunqi Ma, Chang-Joo Lee and Jang-Su Park

Antibiotics 2020, 9(9), 541; https://doi.org/10.3390/antibiotics9090541 - 26 Aug 2020

Cited by 30 | Viewed by 8515

Abstract

Bacteria can produce recombinant proteins quickly and cost effectively. However, their physiological properties limit their use for the production of proteins in their native form, especially polypeptides that are subjected to major post-translational modifications. Proteins that rely on disulfide bridges for their stability [...] Read more.

Bacteria can produce recombinant proteins quickly and cost effectively. However, their physiological properties limit their use for the production of proteins in their native form, especially polypeptides that are subjected to major post-translational modifications. Proteins that rely on disulfide bridges for their stability are difficult to produce in Escherichia coli. The bacterium offers the least costly, simplest, and fastest method for protein production. However, it is difficult to produce proteins with a very large size. Saccharomyces cerevisiae and Pichia pastoris are the most commonly used yeast species for protein production. At a low expense, yeasts can offer high protein yields, generate proteins with a molecular weight greater than 50 kDa, extract signal sequences, and glycosylate proteins. Both eukaryotic and prokaryotic species maintain reducing conditions in the cytoplasm. Hence, the formation of disulfide bonds is inhibited. These bonds are formed in eukaryotic cells during the export cycle, under the oxidizing conditions of the endoplasmic reticulum. Bacteria do not have an advanced subcellular space, but in the oxidizing periplasm, they exhibit both export systems and enzymatic activities directed at the formation and quality of disulfide bonds. Here, we discuss current techniques used to target eukaryotic and prokaryotic species for the generation of correctly folded proteins with disulfide bonds. Full article

(This article belongs to the Special Issue Synthesis and Utility of Antimicrobial Peptides)

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20 pages, 2066 KiB

Open AccessReview

Development and Challenges of Antimicrobial Peptides for Therapeutic Applications

by Charles H. Chen and Timothy K. Lu

Antibiotics 2020, 9(1), 24; https://doi.org/10.3390/antibiotics9010024 - 13 Jan 2020

Cited by 380 | Viewed by 25593

Abstract

More than 3000 antimicrobial peptides (AMPs) have been discovered, seven of which have been approved by the U.S. Food and Drug Administration (FDA). Now commercialized, these seven peptides have mostly been utilized for topical medications, though some have been injected into the body [...] Read more.

More than 3000 antimicrobial peptides (AMPs) have been discovered, seven of which have been approved by the U.S. Food and Drug Administration (FDA). Now commercialized, these seven peptides have mostly been utilized for topical medications, though some have been injected into the body to treat severe bacterial infections. To understand the translational potential for AMPs, we analyzed FDA-approved drugs in the FDA drug database. We examined their physicochemical properties, secondary structures, and mechanisms of action, and compared them with the peptides in the AMP database. All FDA-approved AMPs were discovered in Gram-positive soil bacteria, and 98% of known AMPs also come from natural sources (skin secretions of frogs and toxins from different species). However, AMPs can have undesirable properties as drugs, including instability and toxicity. Thus, the design and construction of effective AMPs require an understanding of the mechanisms of known peptides and their effects on the human body. This review provides an overview to guide the development of AMPs that can potentially be used as antimicrobial drugs. Full article

(This article belongs to the Special Issue Synthesis and Utility of Antimicrobial Peptides)

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