Antibiotics

Editorial

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2 pages, 172 KiB

Open AccessEditorial

Antibacterial Peptides

by Jean-Marc Sabatier

Antibiotics 2020, 9(4), 142; https://doi.org/10.3390/antibiotics9040142 - 26 Mar 2020

Cited by 6 | Viewed by 3210

Abstract

As natural host defense compounds produced by numerous prokaryotic and eukaryotic life forms, antimicrobial peptides (AMPs) are now emerging as solid candidate chemotherapeutic drugs to fight against the various types of pathogenic Gram-positive and Gram-negative bacteria, especially those resistant to current antibiotics [...] [...] Read more.

As natural host defense compounds produced by numerous prokaryotic and eukaryotic life forms, antimicrobial peptides (AMPs) are now emerging as solid candidate chemotherapeutic drugs to fight against the various types of pathogenic Gram-positive and Gram-negative bacteria, especially those resistant to current antibiotics [...] Full article

(This article belongs to the Special Issue Antibacterial Peptides)

Research

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8 pages, 910 KiB

Open AccessArticle

Tissue Specificity in Social Context-Dependent lysozyme Expression in Bumblebees

by H. Michael G. Lattorff

Antibiotics 2020, 9(3), 130; https://doi.org/10.3390/antibiotics9030130 - 20 Mar 2020

Cited by 4 | Viewed by 2585

Abstract

Group living at high densities may result in the enhanced transmission of pathogens. Social insects are obligate group-living species, which often also exhibit high relatedness and frequent social interactions amongst individuals, resulting in a high risk of disease spread. Social species seem to [...] Read more.

Group living at high densities may result in the enhanced transmission of pathogens. Social insects are obligate group-living species, which often also exhibit high relatedness and frequent social interactions amongst individuals, resulting in a high risk of disease spread. Social species seem to exhibit immune systems that provide colonies of social insects with a certain level of flexibility for adjustment of immune activity according to the risk of disease spread. In bumblebees, Bombus terrestris, it was demonstrated that in group-kept individuals, immune component activity and immune gene expression is increased, potentially as a prophylactic adaptation. Here, I tested whether social environment influences the gene expression pattern of two lysozyme genes, which are components of the antimicrobial response of the bumblebee. In addition, I tested gene expression activation in different tissues (gut, fat body). The analysis revealed that the gene, the density of individuals, the tissue, and the interaction of the latter are the main factors that influence the expression of lysozyme genes. This is the first report of a tissue-specific response towards the social environment. This has implications for gene regulation, which must be responsive to social context-dependent information. Full article

(This article belongs to the Special Issue Antibacterial Peptides)

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16 pages, 1828 KiB

Open AccessArticle

A Rapid Fluorescence-Based Microplate Assay to Investigate the Interaction of Membrane Active Antimicrobial Peptides with Whole Gram-Positive Bacteria

by Gerard Boix-Lemonche, Maria Lekka and Barbara Skerlavaj

Antibiotics 2020, 9(2), 92; https://doi.org/10.3390/antibiotics9020092 - 19 Feb 2020

Cited by 38 | Viewed by 7106

Abstract

Background: Membrane-active antimicrobial peptides (AMPs) are interesting candidates for the development of novel antimicrobials. Although their effects were extensively investigated in model membrane systems, interactions of AMPs with living microbial membranes are less known due to their complexity. The aim of the present [...] Read more.

Background: Membrane-active antimicrobial peptides (AMPs) are interesting candidates for the development of novel antimicrobials. Although their effects were extensively investigated in model membrane systems, interactions of AMPs with living microbial membranes are less known due to their complexity. The aim of the present study was to develop a rapid fluorescence-based microplate assay to analyze the membrane effects of AMPs in whole Staphylococcus aureus and Staphylococcus epidermidis. Methods: Bacteria were exposed to bactericidal and sub-inhibitory concentrations of two membrane-active AMPs in the presence of the potential-sensitive dye 3,3′-dipropylthiadicarbocyanine iodide (diSC₃(5)) and the DNA staining dye propidium iodide (PI), to simultaneously monitor and possibly distinguish membrane depolarization and membrane permeabilization. Results: The ion channel-forming gramicidin D induced a rapid increase of diSC₃(5), but not PI fluorescence, with slower kinetics at descending peptide concentrations, confirming killing due to membrane depolarization. The pore-forming melittin, at sub-MIC and bactericidal concentrations, caused, respectively, an increase of PI fluorescence in one or both dyes simultaneously, suggesting membrane permeabilization as a key event. Conclusions: This assay allowed the distinction between specific membrane effects, and it could be applied in the mode of action studies as well as in the screening of novel membrane-active AMPs. Full article

(This article belongs to the Special Issue Antibacterial Peptides)

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13 pages, 2415 KiB

Open AccessArticle

Ib-M6 Antimicrobial Peptide: Antibacterial Activity against Clinical Isolates of Escherichia coli and Molecular Docking

by J. M. Flórez-Castillo, P. Rondón-Villareal, J. L. Ropero-Vega, S. Y. Mendoza-Espinel, J. A. Moreno-Amézquita, K. D. Méndez-Jaimes, A. E. Farfán-García, S. Y. Gómez-Rangel and Oscar Gilberto Gómez-Duarte

Antibiotics 2020, 9(2), 79; https://doi.org/10.3390/antibiotics9020079 - 12 Feb 2020

Cited by 11 | Viewed by 4778

Abstract

The Ib-M6 peptide has antibacterial activity against non-pathogenic Escherichia coli K-12 strain. The first part of this study determines the antibacterial activity of Ib-M6 against fourteen pathogenic strains of E. coli O157:H7. Susceptibility assay showed that Ib-M6 had values of Minimum Inhibitory Concentration [...] Read more.

The Ib-M6 peptide has antibacterial activity against non-pathogenic Escherichia coli K-12 strain. The first part of this study determines the antibacterial activity of Ib-M6 against fourteen pathogenic strains of E. coli O157:H7. Susceptibility assay showed that Ib-M6 had values of Minimum Inhibitory Concentration (MIC) lower than streptomycin, used as a reference antibiotic. Moreover, to predict the possible interaction between Ib-M6 and outer membrane components of E. coli, we used molecular docking simulations where FhuA protein and its complex with Lipopolysaccharide (LPS–FhuA) were used as targets of the peptide. FhuA/Ib-M6 complexes had energy values between −39.5 and −40.5 Rosetta Energy Units (REU) and only one hydrogen bond. In contrast, complexes between LPS–FhuA and Ib-M6 displayed energy values between −25.6 and −40.6 REU, and the presence of five possible hydrogen bonds. Hence, the antimicrobial activity of Ib-M6 peptide shown in the experimental assays could be caused by its interaction with the outer membrane of E. coli. Full article

(This article belongs to the Special Issue Antibacterial Peptides)

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20 pages, 4857 KiB

Open AccessArticle

Trematocine, a Novel Antimicrobial Peptide from the Antarctic Fish Trematomus bernacchii: Identification and Biological Activity

by Giulia Della Pelle, Giulia Perà, Maria Cristina Belardinelli, Marco Gerdol, Martina Felli, Silvia Crognale, Giuseppe Scapigliati, Francesca Ceccacci, Francesco Buonocore and Fernando Porcelli

Antibiotics 2020, 9(2), 66; https://doi.org/10.3390/antibiotics9020066 - 6 Feb 2020

Cited by 17 | Viewed by 4233

Abstract

Antimicrobial peptides (AMPs) are short peptides active against a wide range of pathogens and, therefore, they are considered a useful alternative to conventional antibiotics. We have identified a new AMP in a transcriptome derived from the Antarctic fish Trematomus bernacchii. This peptide, [...] Read more.

Antimicrobial peptides (AMPs) are short peptides active against a wide range of pathogens and, therefore, they are considered a useful alternative to conventional antibiotics. We have identified a new AMP in a transcriptome derived from the Antarctic fish Trematomus bernacchii. This peptide, named Trematocine, has been investigated for its expression both at the basal level and after in vivo immunization with an endemic Antarctic bacterium (Psychrobacter sp. TAD1). Results agree with the expected behavior of a fish innate immune component, therefore we decided to synthesize the putative mature sequence of Trematocine to determine the structure, the interaction with biological membranes, and the biological activity. We showed that Trematocine folds into a α-helical structure in the presence of both zwitterionic and anionic charged vesicles. We demonstrated that Trematocine has a highly specific interaction with anionic charged vesicles and that it can kill Gram-negative bacteria, possibly via a carpet like mechanism. Moreover, Trematocine showed minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against selected Gram-positive and Gram-negative bacteria similar to other AMPs isolated from Antarctic fishes. The peptide is a possible candidate for a new drug as it does not show any haemolytic or cytotoxic activity against mammalian cells at the concentration needed to kill the tested bacteria. Full article

(This article belongs to the Special Issue Antibacterial Peptides)

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8 pages, 677 KiB

Open AccessArticle

Predicting Antimicrobial and Other Cysteine-Rich Peptides in 1267 Plant Transcriptomes

by Andrey Shelenkov, Anna Slavokhotova and Tatyana Odintsova

Antibiotics 2020, 9(2), 60; https://doi.org/10.3390/antibiotics9020060 - 4 Feb 2020

Cited by 19 | Viewed by 4274

Abstract

Antimicrobial peptides (AMPs) are a key component of innate immunity in various organisms including bacteria, insects, mammals, and plants. Their mode of action decreases the probability of developing resistance in pathogenic organisms, which makes them a promising object of study. However, molecular biology [...] Read more.

Antimicrobial peptides (AMPs) are a key component of innate immunity in various organisms including bacteria, insects, mammals, and plants. Their mode of action decreases the probability of developing resistance in pathogenic organisms, which makes them a promising object of study. However, molecular biology methods for searching for AMPs are laborious and expensive, especially for plants. Earlier, we developed a computational pipeline for identifying potential AMPs based on the cysteine motifs they usually possess. Since most motifs are too species-specific, a wide-scale screening of novel data is required to maintain the accuracy of searching algorithms. We have performed a search for potential AMPs in 1267 plant transcriptomes using our pipeline. On average, 50–150 peptides were revealed in each transcriptome. The data was verified by a BLASTp search in nr database to confirm peptide functions and by using random nucleotide sequences to estimate the fraction of erroneous predictions. The datasets obtained will be useful both for molecular biologists investigating AMPs in various organisms and for bioinformaticians developing novel algorithms of motif searching in transcriptomic and genomic sequences. The results obtained will represent a good reference point for future investigations in the fields mentioned above. Full article

(This article belongs to the Special Issue Antibacterial Peptides)

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13 pages, 1950 KiB

Open AccessArticle

Inhibitory Activity of a Scorpion Defensin BmKDfsin3 against Hepatitis C Virus

by Yuting Cheng, Fang Sun, Songryong Li, Minjun Gao, Luyao Wang, Moustafa Sarhan, Mohamed A. Abdel-Rahman, Wenxin Li, Hang Fai Kwok, Yingliang Wu and Zhijian Cao

Antibiotics 2020, 9(1), 33; https://doi.org/10.3390/antibiotics9010033 - 17 Jan 2020

Cited by 20 | Viewed by 4650

Abstract

Hepatitis C virus (HCV) infection is a major worldwide health problem which can cause chronic hepatitis, liver fibrosis and hepatocellular carcinoma (HCC). There is still no vaccine to prevent HCV infection. Currently, the clinical treatment of HCV infection mainly relies on the use [...] Read more.

Hepatitis C virus (HCV) infection is a major worldwide health problem which can cause chronic hepatitis, liver fibrosis and hepatocellular carcinoma (HCC). There is still no vaccine to prevent HCV infection. Currently, the clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) which are expensive and have side effects. Here, BmKDfsin3, a scorpion defensin from the venom of Mesobuthus martensii Karsch, is found to dose-dependently inhibit HCV infection at noncytotoxic concentrations and affect viral attachment and post-entry in HCV life cycle. Further experimental results show that BmKDfsin3 not only suppresses p38 mitogen-activated protein kinase (MAPK) activation of HCV-infected Huh7.5.1 cells, but also inhibits p38 activation of Huh7.5.1 cells stimulated by tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) or lipopolysaccharide (LPS). BmKDfsin3 is also revealed to enter into cells. Using an upstream MyD88 dimerization inhibitor ST2345 or kinase IRAK-1/4 inhibitor I, the inhibition of p38 activation represses HCV replication in vitro. Taken together, a scorpion defensin BmKDfsin3 inhibits HCV replication, related to regulated p38 MAPK activation. Full article

(This article belongs to the Special Issue Antibacterial Peptides)

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9 pages, 776 KiB

Open AccessArticle

Designed Antimicrobial Peptides for Topical Treatment of Antibiotic Resistant Acne Vulgaris

by Kathryn W. Woodburn, Jesse Jaynes and L. Edward Clemens

Antibiotics 2020, 9(1), 23; https://doi.org/10.3390/antibiotics9010023 - 13 Jan 2020

Cited by 26 | Viewed by 5427

Abstract

Acne vulgaris, caused by the Gram-positive bacterium Cutibacterium acnes, is a prevalent dermatologic condition with substantial cutaneous and psychological morbidity. Mild acne is treated with topical antibiotics with more severe inflammatory forms requiring the prolonged use of oral antibiotics, resulting in antimicrobial [...] Read more.

Acne vulgaris, caused by the Gram-positive bacterium Cutibacterium acnes, is a prevalent dermatologic condition with substantial cutaneous and psychological morbidity. Mild acne is treated with topical antibiotics with more severe inflammatory forms requiring the prolonged use of oral antibiotics, resulting in antimicrobial resistance development. Innovative treatment alternatives, providing complete microbicidal eradication with minimal safety issues and limited susceptibility to microbial resistance, are fervently sought. Designed antimicrobial peptides (dAMPs) are engineered analogs of naturally occurring AMPs that possess a reduced likelihood of developing bacterial resistance. Seven novel dAMP sequences were screened for in vitro bactericidal effectiveness against antibiotic resistant C. acnes clinical isolates. Five peptides (RP444, RP551, RP554, RP556, and RP557) exhibited potent in vitro antibacterial activity. The Therapeutic Index, a measure of specificity for killing multidrug resistant C. acnes over mammalian cells, was determined using bioluminescent human keratinocytes. The Therapeutic Index was highest for the disulfide dAMP, RP556, with a value of 130. The lead dAMP candidate RP556, was further evaluated in a multidrug-resistant C. acnes intradermal murine infection model. A topical application of 5 mg/mL RP556 (0.5%) eliminated infection. If these preclinical results are translated clinically, dAMPs may become a viable topical monotherapy for the treatment of recalcitrant acne infections. Full article

(This article belongs to the Special Issue Antibacterial Peptides)

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15 pages, 2806 KiB

Open AccessArticle

Properties of an Antimicrobial Molecule Produced by an Escherichia coli Champion

by Sarah-Jo Paquette and Tim Reuter

Antibiotics 2020, 9(1), 6; https://doi.org/10.3390/antibiotics9010006 - 21 Dec 2019

Cited by 5 | Viewed by 7102

Abstract

Over recent decades, the number and frequency of severe pathogen infections have been increasing. Pathogen mitigation strategies in human medicine or in livestock operations are vital to combat emerging arsenals of bacterial virulence and defense mechanisms. Since the emergence of antimicrobial resistance, the [...] Read more.

Over recent decades, the number and frequency of severe pathogen infections have been increasing. Pathogen mitigation strategies in human medicine or in livestock operations are vital to combat emerging arsenals of bacterial virulence and defense mechanisms. Since the emergence of antimicrobial resistance, the competitive nature of bacteria has been considered for the potential treatment or mitigation of pathogens. Previously, we identified a strong E. coli competitor with probiotic properties producing a diffusible antimicrobial molecule(s) that inhibited the growth of Shiga toxin-producing E. coli (STEC). Our current objective was to isolate and examine the properties of this antimicrobial molecule(s). Molecules were isolated by filter sterilization after 12 h incubation, and bacterial inhibition was compared to relevant controls. Isolated antimicrobial molecule(s) and controls were subjected to temperature, pH, or protease digestion treatments. Changes in inhibition properties were evaluated by comparing the incremental cell growth in the presence of treated and untreated antimicrobial molecule(s). No treatment affected the antimicrobial molecule(s) properties of STEC inhibition, suggesting that at least one molecule produced is an efficacious microcin. The molecule persistence to physiochemical and enzymatic treatments could open a wide window to technical industry-scale applications. Full article

(This article belongs to the Special Issue Antibacterial Peptides)

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16 pages, 3863 KiB

Open AccessArticle

Increases in Hydrophilicity and Charge on the Polar Face of Alyteserin 1c Helix Change its Selectivity towards Gram-Positive Bacteria

by Yamil Liscano, Constain H. Salamanca, Lina Vargas, Stefania Cantor, Valentina Laverde-Rojas and José Oñate-Garzón

Antibiotics 2019, 8(4), 238; https://doi.org/10.3390/antibiotics8040238 - 27 Nov 2019

Cited by 36 | Viewed by 4595

Abstract

Recently, resistance of pathogens towards conventional antibiotics has increased, representing a threat to public health globally. As part of the fight against this, studies on alternative antibiotics such as antimicrobial peptides have been performed, and it has been shown that their sequence and [...] Read more.

Recently, resistance of pathogens towards conventional antibiotics has increased, representing a threat to public health globally. As part of the fight against this, studies on alternative antibiotics such as antimicrobial peptides have been performed, and it has been shown that their sequence and structure are closely related to their antimicrobial activity. Against this background, we here evaluated the antibacterial activity of two peptides developed by solid-phase synthesis, Alyteserin 1c (WT) and its mutant derivative (ΔM), which shows increased net charge and reduced hydrophobicity. These structural characteristics were modified as a result of amino acid substitutions on the polar face of the WT helix. The minimum inhibitory concentration (MIC) of both peptides was obtained in Gram-positive and Gram-negative bacteria. The results showed that the rational substitutions of the amino acids increased the activity in Gram-positive bacteria, especially against Staphylococcus aureus, for which the MIC was one-third of that for the WT analog. In contrast to the case for Gram-positive bacteria, these substitutions decreased activity against Gram-negative bacteria, especially in Escherichia coli, for which the MIC was eight-fold higher than that exhibited by the WT peptide. To understand this, models of the peptide behavior upon interacting with membranes of E. coli and S. aureus created using molecular dynamics were studied and it was determined that the helical stability of the peptide is indispensable for antimicrobial activity. The hydrogen bonds between the His20 of the peptides and the phospholipids of the membranes should modulate the selectivity associated with structural stability at the carboxy-terminal region of the peptides. Full article

(This article belongs to the Special Issue Antibacterial Peptides)

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Review

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21 pages, 3373 KiB

Open AccessReview

More Than a Pore: A Current Perspective on the In Vivo Mode of Action of the Lipopeptide Antibiotic Daptomycin

by Declan Alan Gray and Michaela Wenzel

Antibiotics 2020, 9(1), 17; https://doi.org/10.3390/antibiotics9010017 - 3 Jan 2020

Cited by 78 | Viewed by 9916

Abstract

Daptomycin is a cyclic lipopeptide antibiotic, which was discovered in 1987 and entered the market in 2003. To date, it serves as last resort antibiotic to treat complicated skin infections, bacteremia, and right-sided endocarditis caused by Gram-positive pathogens, most prominently methicillin-resistant Staphylococcus aureus [...] Read more.

Daptomycin is a cyclic lipopeptide antibiotic, which was discovered in 1987 and entered the market in 2003. To date, it serves as last resort antibiotic to treat complicated skin infections, bacteremia, and right-sided endocarditis caused by Gram-positive pathogens, most prominently methicillin-resistant Staphylococcus aureus. Daptomycin was the last representative of a novel antibiotic class that was introduced to the clinic. It is also one of the few membrane-active compounds that can be applied systemically. While membrane-active antibiotics have long been limited to topical applications and were generally excluded from systemic drug development, they promise slower resistance development than many classical drugs that target single proteins. The success of daptomycin together with the emergence of more and more multi-resistant superbugs attracted renewed interest in this compound class. Studying daptomycin as a pioneering systemic membrane-active compound might help to pave the way for future membrane-targeting antibiotics. However, more than 30 years after its discovery, the exact mechanism of action of daptomycin is still debated. In particular, there is a prominent discrepancy between in vivo and in vitro studies. In this review, we discuss the current knowledge on the mechanism of daptomycin against Gram-positive bacteria and try to offer explanations for these conflicting observations. Full article

(This article belongs to the Special Issue Antibacterial Peptides)

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