Alternatives to Antibiotics: Bacteriocins and Antimicrobial Peptides

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

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 35371

Special Issue Editor


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Guest Editor
Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal
Interests: antimicrobial peptides; hepcidin; antibiotic resistance; iron metabolism; iron overload; anemia; erythropoiesis; innate immunity; fish immunology; bacterial, viral and parasitic diseases
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Special Issue Information

Dear Colleagues,

In recent years, the often indiscriminate use of antibiotics to control infectious diseases has led to an increase in multidrug antimicrobial resistance, causing serious problems in several fields of human medicine, as well as in animal and food production and other agricultural activities. Therefore, this has become a critical issue that urgently presses for the discovery and development of new antimicrobial agents. Among the different alternatives studied, antimicrobial peptides and bacteriocins are some of the most promising candidates. Antimicrobial peptides are host defense peptides with a broad spectrum of activity, not only against bacteria, but also against fungi, parasites, and even enveloped viruses, and are less likely to induce resistance. Bacteriocins are bactericidal peptides produced by bacteria, that also exhibit antimicrobial activity with variable spectrum, depending on the peptide. Both these antimicrobial agents are already implemented in some areas, though to a very limited extent; therefore, their true potential remains unlocked. This Special Issue is looking for manuscript submissions on all aspects of antibacterial peptides and bacteriocins, both old and new, and on how they can contribute to further benefiting human and veterinary health. Original research manuscripts, short communications, and reviews are welcomed.

Dr. João Vilares Neves
Guest Editor

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Keywords

  • antimicrobial peptides
  • bacteriocins
  • antimicrobial resistance
  • antibiotics
  • infectious diseases
  • human health
  • veterinary health

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Published Papers (9 papers)

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Editorial

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4 pages, 189 KiB  
Editorial
Editorial for Special Issue “Alternatives to Antibiotics: Bacteriocins and Antimicrobial Peptides”
by Joao V. Neves
Antibiotics 2022, 11(7), 860; https://doi.org/10.3390/antibiotics11070860 - 27 Jun 2022
Cited by 1 | Viewed by 1472
Abstract
The discovery of penicillin in 1928 by Sir Alexander Fleming, and its later introduction as an antibiotic in the early 1940s, was a gamechanger for the entire medical field [...] Full article
(This article belongs to the Special Issue Alternatives to Antibiotics: Bacteriocins and Antimicrobial Peptides)

Research

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21 pages, 5100 KiB  
Article
Effect of Lactobacillus plantarum Biofilms on the Adhesion of Escherichia coli to Urinary Tract Devices
by Fábio M. Carvalho, Rita Teixeira-Santos, Filipe J. M. Mergulhão and Luciana C. Gomes
Antibiotics 2021, 10(8), 966; https://doi.org/10.3390/antibiotics10080966 - 11 Aug 2021
Cited by 23 | Viewed by 4969
Abstract
Novel technologies to prevent biofilm formation on urinary tract devices (UTDs) are continually being developed, with the ultimate purpose of reducing the incidence of urinary infections. Probiotics have been described as having the ability to displace adhering uropathogens and inhibit microbial adhesion to [...] Read more.
Novel technologies to prevent biofilm formation on urinary tract devices (UTDs) are continually being developed, with the ultimate purpose of reducing the incidence of urinary infections. Probiotics have been described as having the ability to displace adhering uropathogens and inhibit microbial adhesion to UTD materials. This work aimed to evaluate the effect of pre-established Lactobacillus plantarum biofilms on the adhesion of Escherichia coli to medical-grade silicone. The optimal growth conditions of lactobacilli biofilms on silicone were first assessed in 12-well plates. Then, biofilms of L. plantarum were placed in contact with E. coli suspensions for up to 24 h under quasi-static conditions. Biofilm monitoring was performed by determining the number of culturable cells and by confocal laser scanning microscopy (CLSM). Results showed significant reductions of 76%, 77% and 99% in E. coli culturability after exposure to L. plantarum biofilms for 3, 6 and 12 h, respectively, corroborating the CLSM analysis. The interactions between microbial cell surfaces and the silicone surface with and without L. plantarum biofilms were also characterized using contact angle measurements, where E. coli was shown to be thermodynamically less prone to adhere to L. plantarum biofilms than to silicone. Thus, this study suggests the use of probiotic cells as potential antibiofilm agents for urinary tract applications. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics: Bacteriocins and Antimicrobial Peptides)
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21 pages, 3484 KiB  
Article
Antimicrobial Potential of Microorganisms Isolated from the Bottom Sediments of Lake Baikal
by Olga Babich, Margarita Shevchenko, Svetlana Ivanova, Valery Pavsky, Maria Zimina, Svetlana Noskova, Veronika Anohova, Evgeny Chupakhin and Stanislav Sukhikh
Antibiotics 2021, 10(8), 927; https://doi.org/10.3390/antibiotics10080927 - 30 Jul 2021
Cited by 6 | Viewed by 2673
Abstract
Extremophilic microorganisms attract researchers by their unique characteristics, primarily antagonistic ones, acquired in the process of survival in extreme natural conditions. The antimicrobial potential of the metabolites of these microorganisms is quite broad, from the food industry to therapeutic drugs. Microbial mats of [...] Read more.
Extremophilic microorganisms attract researchers by their unique characteristics, primarily antagonistic ones, acquired in the process of survival in extreme natural conditions. The antimicrobial potential of the metabolites of these microorganisms is quite broad, from the food industry to therapeutic drugs. Microbial mats of Lake Baikal are a source of unique and diverse microorganisms. The study aimed to evaluate the antimicrobial activity of bacterial strains isolated from the bottom sediments of the lake. Using heterotrophic growth conditions, seven bacterial strains were isolated from samples collected in several coastal zones of Lake Baikal. Thisstudy identified both widespread strains of the genera Pseudomonas and Bacillus and rare genera Micrococcus and Acinetobacterrepresentatives. Metabolites of five strains were found to have a broad spectrum of antimicrobial activity. Four large fractions of metabolites of the isolated strains wereidentified. Two peptides of the isolated fractions of metabolites (one is produced by microorganisms of all five isolated strains, another—only by Pseudomonas putida) are low molecular weight oligopeptides. These peptides were proved to be bacteriocins. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics: Bacteriocins and Antimicrobial Peptides)
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15 pages, 2234 KiB  
Article
Antimicrobial Activity of the Circular Bacteriocin AS-48 against Clinical Multidrug-Resistant Staphylococcus aureus
by Cristina Velázquez-Suárez, Rubén Cebrián, Carmen Gasca-Capote, Antonio Sorlózano-Puerto, José Gutiérrez-Fernández, Manuel Martínez-Bueno, Mercedes Maqueda and Eva Valdivia
Antibiotics 2021, 10(8), 925; https://doi.org/10.3390/antibiotics10080925 - 30 Jul 2021
Cited by 10 | Viewed by 3162
Abstract
The treatment and hospital-spread-control of methicillin-resistant Staphylococcus aureus (MRSA) is an important challenge since these bacteria are involved in a considerable number of nosocomial infections that are difficult to treat and produce prolonged hospitalization, thus also increasing the risk of death. In fact, [...] Read more.
The treatment and hospital-spread-control of methicillin-resistant Staphylococcus aureus (MRSA) is an important challenge since these bacteria are involved in a considerable number of nosocomial infections that are difficult to treat and produce prolonged hospitalization, thus also increasing the risk of death. In fact, MRSA strains are frequently resistant to all β-lactam antibiotics, and co-resistances with other drugs such as macrolides, aminoglycosides, and lincosamides are usually reported, limiting the therapeutical options. To this must be added that the ability of these bacteria to form biofilms on hospital surfaces and devices confer high antibiotic resistance and favors horizontal gene transfer of genetic-resistant mobile elements, the spreading of infections, and relapses. Here, we genotypically and phenotypically characterized 100 clinically isolated S. aureus for their resistance to 18 antibiotics (33% of them were OXA resistant MRSA) and ability to form biofilms. From them, we selected 48 strains on the basis on genotype group, antimicrobial-resistance profile, and existing OXA resistance to be assayed against bacteriocin AS-48. The results showed that AS-48 was active against all strains, regardless of their clinical source, genotype, antimicrobial resistance profile, or biofilm formation capacity, and this activity was enhanced in the presence of the antimicrobial peptide lysozyme. Finally, we explored the effect of AS-48 on formed S. aureus biofilms, observing a reduction in S. aureus S-33 viability. Changes in the matrix structure of the biofilms as well as in the cell division process were observed with scanning electron microscopy in both S-33 and S-48 S. aureus strains. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics: Bacteriocins and Antimicrobial Peptides)
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11 pages, 773 KiB  
Article
Long-Lasting Stable Expression of Human LL-37 Antimicrobial Peptide in Transgenic Barley Plants
by Malihe Mirzaee, Edita Holásková, Alžbeta Mičúchová, David J. Kopečný, Zhila Osmani and Ivo Frébort
Antibiotics 2021, 10(8), 898; https://doi.org/10.3390/antibiotics10080898 - 23 Jul 2021
Cited by 14 | Viewed by 4252
Abstract
Antimicrobial peptides play a crucial role in the innate immune system of multicellular organisms. LL-37 is the only known member of the human cathelicidin family. As well as possessing antibacterial properties, it is actively involved in various physiological responses in eukaryotic cells. Accordingly, [...] Read more.
Antimicrobial peptides play a crucial role in the innate immune system of multicellular organisms. LL-37 is the only known member of the human cathelicidin family. As well as possessing antibacterial properties, it is actively involved in various physiological responses in eukaryotic cells. Accordingly, there is considerable interest in large-scale, low-cost, and microbial endotoxin-free production of LL-37 recombinant peptides for pharmaceutical applications. As a heterologous expression biofactory, we have previously obtained homologous barley (Hordeum vulgare L.) as an attractive vehicle for producing recombinant human LL-37 in the grain storage compartment, endosperm. The long-term stability of expression and inheritance of transgenes is necessary for the successful commercialization of recombinant proteins. Here, we report the stable inheritance and expression of the LL-37 gene in barley after six generations, including two consecutive seasons of experimental field cultivation. The transgenic plants showed normal growth and remained fertile. Based on the bacteria viability test, the produced peptide LL-37 retained high antibacterial activity. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics: Bacteriocins and Antimicrobial Peptides)
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23 pages, 7682 KiB  
Article
A C-Type Lectin Highly Expressed in Portunus trituberculatus Intestine Functions in AMP Regulation and Prophenoloxidase Activation
by Yuan Liu, Yue Su, Ao Zhang and Zhaoxia Cui
Antibiotics 2021, 10(5), 541; https://doi.org/10.3390/antibiotics10050541 - 7 May 2021
Cited by 15 | Viewed by 2355
Abstract
A C-type lectin (PtCLec2) from Portunus trituberculatus was identified for characterization of its role in defense and innate immunity. PtCLec2 contains a single carbohydrate-recognition domain (CRD) with a conserved QPD motif, which was predicted to have galactose specificity. The mRNA expression of PtCLec2 [...] Read more.
A C-type lectin (PtCLec2) from Portunus trituberculatus was identified for characterization of its role in defense and innate immunity. PtCLec2 contains a single carbohydrate-recognition domain (CRD) with a conserved QPD motif, which was predicted to have galactose specificity. The mRNA expression of PtCLec2 was predominantly detected in intestine and increased rapidly and significantly upon pathogen challenge. The recombinant PtCLec2 (rPtCLec2) could bind various microorganisms and PAMPs with weak binding ability to yeast and PGN. It agglutinated the tested Gram-negative bacteria (Vibrio alginolyticus and Pseudomonas aeruginosa), Gram-positive bacteria (Staphylococcus aureus and Micrococcus luteus), and rabbit erythrocytes in the presence of exogenous Ca2+, and these agglutination activities were suppressed by LPS, d-galactose, and d-mannose. Further, rPtCLec2 enhanced phagocytosis and clearance of V. alginolyticus, and displayed inhibitory activities against the tested bacteria. Knockdown of PtCLec2 decreased the transcription of two phagocytosis genes (PtArp and PtMyosin), three prophenoloxidase (proPO) system-related genes (PtPPAF, PtcSP1, and PtproPO), six antimicrobial peptides (AMPs) (PtALF4-7, PtCrustin1, and PtCrustin3), and PtRelish but upregulated the expression levels of PtJNK, PtPelle, and PtTLR. These results collectively indicate that PtCLec2 might perform its immune recognition function via binding and agglutination, and mediate pathogen elimination via regulating hemocyte phagocytosis, AMP synthesis, and proPO activation. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics: Bacteriocins and Antimicrobial Peptides)
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19 pages, 5430 KiB  
Article
Genome Characterization of Lactiplantibacillus plantarum Strain UTNGt2 Originated from Theobroma grandiflorum (White Cacao) of Ecuadorian Amazon: Antimicrobial Peptides from Safety to Potential Applications
by Gabriela N. Tenea and Clara Ortega
Antibiotics 2021, 10(4), 383; https://doi.org/10.3390/antibiotics10040383 - 3 Apr 2021
Cited by 30 | Viewed by 4629
Abstract
The genome characterization of the Lactiplantibacillus plantarum strain UTNGt2, isolated from wild copoazu or white cacao (Theobroma grandiflorum), is described. A total of 31 contigs is assembled with a total length of 3,264,448 bases, with all contigs matching the core genome [...] Read more.
The genome characterization of the Lactiplantibacillus plantarum strain UTNGt2, isolated from wild copoazu or white cacao (Theobroma grandiflorum), is described. A total of 31 contigs is assembled with a total length of 3,264,448 bases, with all contigs matching the core genome of different groups in the database. The genome size is 3,540,752 bases with GC content of 44.53% and the genome repeat sequences constitute around 457,386 bases of the assembly. The UTNGt2 matches the Lactiplantibacillus plantarum genome with 99% identity. The genome contains 3115 genes, 3052 protein-coding genes, assigned with the EggNOG database. On the basis of the results, 745 proteins are classified with an unknown function, from which 128 proteins have no match in the BLASTN database. It also contains 57 tRNAs, 5 copies of 5S rRNA, and 1 copy of tmRNA. Based on gene prediction and annotation results, 9.4% of proteins are involved in carbohydrate transport and metabolism and 8.46% in transcription, 2.36% are responsible for defense mechanisms, 0.5% are responsible for the biosynthesis of secondary metabolites, transport, and catabolism, while 25.11% have an unknown function. The genome revealed the presence of genes involved in riboflavin and folate production, the presence of CRISPR/Cas genes, phage sequences, the absence of acquired antibiotics resistance genes, virulence, and pathogenic factors, suggesting that UTNGt2 is a safe strain. Its highly antimicrobial capacity is related to the presence of two bacteriocin clusters (class IIc) of the sactipeptide class (contig 4) and plantaricin E class (contig 22), as detected by the BAGEL 4 webserver. Several RiPP-like peptides (non-bactericidal ribosomally produced and post-translationally modified peptides), polyketides (PKs), and terpenes were predicted. Whole-genome sequencing analysis revealed that the UTNGt2 strain has diverse bacteriocins with a high inhibitory capacity, thus it is a bacteriocinogenic strain. Considering the safety profile, UTNGt2 is a nonpathogenic, nonvirulent strain with valuable biotechnological traits and can be further exploited for its probiotic and antimicrobial potential in the food industry or as a potential producer strain of antimicrobial peptides as an alternative to conventional antibiotics. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics: Bacteriocins and Antimicrobial Peptides)
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Review

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32 pages, 3725 KiB  
Review
Lipid Transfer Proteins (LTPs)—Structure, Diversity and Roles beyond Antimicrobial Activity
by Vinícius Costa Amador, Carlos André dos Santos-Silva, Lívia Maria Batista Vilela, Marx Oliveira-Lima, Mireli de Santana Rêgo, Ricardo Salas Roldan-Filho, Roberta Lane de Oliveira-Silva, Ayug Bezerra Lemos, Wilson Dias de Oliveira, José Ribamar Costa Ferreira-Neto, Sérgio Crovella and Ana Maria Benko-Iseppon
Antibiotics 2021, 10(11), 1281; https://doi.org/10.3390/antibiotics10111281 - 21 Oct 2021
Cited by 21 | Viewed by 3931
Abstract
Lipid transfer proteins (LTPs) are among the most promising plant-exclusive antimicrobial peptides (AMPs). They figure among the most challenging AMPs from the point of view of their structural diversity, functions and biotechnological applications. This review presents a current picture of the LTP research, [...] Read more.
Lipid transfer proteins (LTPs) are among the most promising plant-exclusive antimicrobial peptides (AMPs). They figure among the most challenging AMPs from the point of view of their structural diversity, functions and biotechnological applications. This review presents a current picture of the LTP research, addressing not only their structural, evolutionary and further predicted functional aspects. Traditionally, LTPs have been identified by their direct isolation by biochemical techniques, whereas omics data and bioinformatics deserve special attention for their potential to bring new insights. In this context, new possible functions have been identified revealing that LTPs are actually multipurpose, with many additional predicted roles. Despite some challenges due to the toxicity and allergenicity of LTPs, a systematic review and search in patent databases, indicate promising perspectives for the biotechnological use of LTPs in human health and also plant defense. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics: Bacteriocins and Antimicrobial Peptides)
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23 pages, 1563 KiB  
Review
Enterococcus spp. as a Producer and Target of Bacteriocins: A Double-Edged Sword in the Antimicrobial Resistance Crisis Context
by Ana C. Almeida-Santos, Carla Novais, Luísa Peixe and Ana R. Freitas
Antibiotics 2021, 10(10), 1215; https://doi.org/10.3390/antibiotics10101215 - 7 Oct 2021
Cited by 36 | Viewed by 6431
Abstract
Enterococcus spp. are one of the most frequent producers of bacteriocins (enterocins), which provides them with an advantage to compete in their natural environment, which is the gut of humans and many animals. The enterocins’ activity against microorganisms from different phylogenetic groups has [...] Read more.
Enterococcus spp. are one of the most frequent producers of bacteriocins (enterocins), which provides them with an advantage to compete in their natural environment, which is the gut of humans and many animals. The enterocins’ activity against microorganisms from different phylogenetic groups has raised interest in Enterococcus spp. in different contexts throughout the last decades, especially in the food industry. Nevertheless, some species can also cause opportunistic life-threatening infections and are frequently multidrug-resistant (MDR). Vancomycin-resistant Enterococcus (VRE), in particular, are an ongoing global challenge given the lack of therapeutic options. In this scenario, bacteriocins can offer a potential solution to this persistent threat, either alone or in combination with other antimicrobials. There are a handful of studies that demonstrate the advantages and applications of bacteriocins, especially against VRE. The purpose of this review is to present a current standpoint about the dual role of Enterococcus spp., from important producers to targets needed to be controlled, and the crucial role that enterocins may have in the expansion of enterococcal populations. Classification and distribution of enterocins, the current knowledge about the bacteriocinome of clinical enterococci, and the challenges of bacteriocin use in the fight against VRE infections are particularly detailed. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics: Bacteriocins and Antimicrobial Peptides)
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