Antimicrobial Peptides in Farm Animals: An Updated Review on Its Diversity, Function, Modes of Action and Therapeutic Prospects

Antimicrobial peptides (AMPs) are the arsenals of the innate host defense system, exhibiting evolutionarily conserved characteristics that are present in practically all forms of life. Recent years have witnessed the emergence of antibiotic-resistant bacteria compounded with a slow discovery rate for new antibiotics that have necessitated scientific efforts to search for alternatives to antibiotics. Research on the identification of AMPs has generated very encouraging evidence that they curb infectious pathologies and are also useful as novel biologics to function as immunotherapeutic agents. Being innate, they exhibit the least cytotoxicity to the host and exerts a wide spectrum of biological activity including low resistance among microbes and increased wound healing actions. Notably, in veterinary science, the constant practice of massive doses of antibiotics with inappropriate withdrawal programs led to a high risk of livestock-associated antimicrobial resistance. Therefore, the world faces tremendous pressure for designing and devising strategies to mitigate the use of antibiotics in animals and keep it safe for posterity. In this review, we illustrate the diversity of farm animal-specific AMPs, and their biochemical foundations, mode of action, and prospective application in clinics. Subsequently, we present the data for their systematic classification under the major and minor groups, antipathogenic action, and allied bioactivities in the host. Finally, we address the limitations of their clinical implementation and envision areas for further advancement.

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Antimicrobial Peptides: Recent Insights on Biotechnological Interventions and Future Perspectives

Protein and Peptide Letters ◽

10.2174/0929866525666181026160852 ◽

2019 ◽

Vol 26 (2) ◽

pp. 79-87 ◽

Cited By ~ 12

Author(s):

Rajeshwari Sinha ◽

Pratyoosh Shukla

Keyword(s):

Antimicrobial Peptides ◽

Gene Editing ◽

Resistant Bacteria ◽

Drug Resistant ◽

Future Perspectives ◽

Antibiotic Resistant ◽

Viable Solution ◽

New Antibiotics ◽

Potential Applications ◽

Critical Public Health

With the unprecedented rise of drug-resistant pathogens, particularly antibiotic-resistant bacteria, and no new antibiotics in the pipeline over the last three decades, the issue of antimicrobial resistance has emerged as a critical public health threat. Antimicrobial Peptides (AMP) have garnered interest as a viable solution to this grave issue and are being explored for their potential antimicrobial applications. Given their low bioavailability in nature, tailoring new AMPs or strategizing approaches for increasing the yield of AMPs, therefore, becomes pertinent. </P><P> The present review focuses on biotechnological interventions directed towards enhanced AMP synthesis and revisits existing genetic engineering and synthetic biology strategies for production of AMPs. This review further underscores the importance and potential applications of advanced gene editing technologies for the synthesis of novel AMPs in future.

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Multiresistant Bacteria Isolated from Intestinal Faeces of Farm Animals in Austria

Antibiotics ◽

10.3390/antibiotics10040466 ◽

2021 ◽

Vol 10 (4) ◽

pp. 466

Author(s):

Herbert Galler ◽

Josefa Luxner ◽

Christian Petternel ◽

Franz F. Reinthaler ◽

Juliana Habib ◽

...

Keyword(s):

Meat Products ◽

Animal Husbandry ◽

Multidrug Resistant ◽

Farm Animals ◽

Resistant Bacteria ◽

Antibiotic Resistant Bacteria ◽

Antibiotic Resistant ◽

E Coli ◽

Multiresistant Bacteria ◽

Vancomycin Resistant

In recent years, antibiotic-resistant bacteria with an impact on human health, such as extended spectrum β-lactamase (ESBL)-containing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), have become more common in food. This is due to the use of antibiotics in animal husbandry, which leads to the promotion of antibiotic resistance and thus also makes food a source of such resistant bacteria. Most studies dealing with this issue usually focus on the animals or processed food products to examine the antibiotic resistant bacteria. This study investigated the intestine as another main habitat besides the skin for multiresistant bacteria. For this purpose, faeces samples were taken directly from the intestines of swine (n = 71) and broiler (n = 100) during the slaughter process and analysed. All samples were from animals fed in Austria and slaughtered in Austrian slaughterhouses for food production. The samples were examined for the presence of ESBL-producing Enterobacteriaceae, MRSA, MRCoNS and VRE. The resistance genes of the isolated bacteria were detected and sequenced by PCR. Phenotypic ESBL-producing Escherichia coli could be isolated in 10% of broiler casings (10 out of 100) and 43.6% of swine casings (31 out of 71). In line with previous studies, the results of this study showed that CTX-M-1 was the dominant ESBL produced by E. coli from swine (n = 25, 83.3%) and SHV-12 from broilers (n = 13, 81.3%). Overall, the frequency of positive samples with multidrug-resistant bacteria was lower than in most comparable studies focusing on meat products.

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Antibiotic Pipeline Coordinators

The Journal of Law Medicine & Ethics ◽

10.1177/1073110518782912 ◽

2018 ◽

Vol 46 (S1) ◽

pp. 25-31 ◽

Cited By ~ 8

Author(s):

Enrico Baraldi ◽

Olof Lindahl ◽

Miloje Savic ◽

David Findlay ◽

Christine Årdal

Keyword(s):

Research And Development ◽

World Health ◽

Resistant Bacteria ◽

Antibiotic Resistant ◽

Priority List ◽

Non Profit ◽

Global Priority ◽

The World ◽

New Antibiotics ◽

Health Organization

The World Health Organization (WHO) has published a global priority list of antibiotic-resistant bacteria to guide research and development (R&D) of new antibiotics. Every pathogen on this list requires R&D activity, but some are more attractive for private sector investments, as evidenced by the current antibacterial pipeline. A “pipeline coordinator” is a governmental/non-profit organization that closely tracks the antibacterial pipeline and actively supports R&D across all priority pathogens employing new financing tools.

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Thinking Outside the Bug: Molecular Targets and Strategies to Overcome Antibiotic Resistance

International Journal of Molecular Sciences ◽

10.3390/ijms20061255 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1255 ◽

Cited By ~ 21

Author(s):

Ana Monserrat-Martinez ◽

Yann Gambin ◽

Emma Sierecki

Keyword(s):

Antibiotic Resistance ◽

Bacterial Infections ◽

Rational Design ◽

Disease Onset ◽

Resistant Bacteria ◽

Antibiotic Resistant ◽

New Antibiotics ◽

Resistant Strains ◽

Vancomycin Resistant ◽

Antibiotic Discovery

Since their discovery in the early 20th century, antibiotics have been used as the primary weapon against bacterial infections. Due to their prophylactic effect, they are also used as part of the cocktail of drugs given to treat complex diseases such as cancer or during surgery, in order to prevent infection. This has resulted in a decrease of mortality from infectious diseases and an increase in life expectancy in the last 100 years. However, as a consequence of administering antibiotics broadly to the population and sometimes misusing them, antibiotic-resistant bacteria have appeared. The emergence of resistant strains is a global health threat to humanity. Highly-resistant bacteria like Staphylococcus aureus (methicillin-resistant) or Enterococcus faecium (vancomycin-resistant) have led to complications in intensive care units, increasing medical costs and putting patient lives at risk. The appearance of these resistant strains together with the difficulty in finding new antimicrobials has alarmed the scientific community. Most of the strategies currently employed to develop new antibiotics point towards novel approaches for drug design based on prodrugs or rational design of new molecules. However, targeting crucial bacterial processes by these means will keep creating evolutionary pressure towards drug resistance. In this review, we discuss antibiotic resistance and new options for antibiotic discovery, focusing in particular on new alternatives aiming to disarm the bacteria or empower the host to avoid disease onset.

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Multidrug-Resistant Bacteria Isolated from Different Aquatic Environments in the North of Spain and South of France

Microorganisms ◽

10.3390/microorganisms8091425 ◽

2020 ◽

Vol 8 (9) ◽

pp. 1425

Author(s):

Lara Pérez-Etayo ◽

David González ◽

José Leiva ◽

Ana Isabel Vitas

Keyword(s):

Wastewater Treatment Plants ◽

Multidrug Resistant ◽

World Health ◽

Resistant Bacteria ◽

Aquatic Environments ◽

Multidrug Resistant Bacteria ◽

Antibiotic Resistant ◽

The North ◽

New Antibiotics ◽

Health Organization

Due to the global progress of antimicrobial resistance, the World Health Organization (WHO) published the list of the antibiotic-resistant “priority pathogens” in order to promote research and development of new antibiotics to the families of bacteria that cause severe and often deadly infections. In the framework of the One Health approach, the surveillance of these pathogens in different environments should be implemented in order to analyze their spread and the potential risk of transmission of antibiotic resistances by food and water. Therefore, the objective of this work was to determine the presence of high and critical priority pathogens included in the aforementioned list in different aquatic environments in the POCTEFA area (North Spain–South France). In addition to these pathogens, detection of colistin-resistant Enterobacteriaceae was included due its relevance as being the antibiotic of choice to treat infections caused by multidrug resistant bacteria (MDR). From the total of 80 analyzed samples, 100% of the wastewater treatment plants (WWTPs) and collectors (from hospitals and slaughterhouses) and 96.4% of the rivers, carried antibiotic resistant bacteria (ARB) against the tested antibiotics. Fifty-five (17.7%) of the isolates were identified as target microorganisms (high and critical priority pathogens of WHO list) and 58.2% (n = 32) of them came from WWTPs and collectors. Phenotypic and genotypic characterization showed that 96.4% were MDR and resistance to penicillins/cephalosporins was the most widespread. The presence of bla genes, KPC-type carbapenemases, mcr-1 and vanB genes has been confirmed. In summary, the presence of clinically relevant MDR bacteria in the studied aquatic environments demonstrates the need to improve surveillance and treatments of wastewaters from slaughterhouses, hospitals and WWTPs, in order to minimize the dispersion of resistance through the effluents of these areas.

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Synergy of action of antimicrobial peptides PG-1 and ChBac3.4 with antiseptics against antibiotic-resistant bacteria

Medical academic journal ◽

10.17816/maj18447-57 ◽

2018 ◽

Vol 18 (4) ◽

pp. 47-57

Author(s):

Maria Sergeyevna Zharkova ◽

Ekaterina S. Umnyakova ◽

Anna G. Afinogenova ◽

Gennady E. Afinogenov ◽

Aleksandr A. Kolobov ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Sodium Hypochlorite ◽

Hemolytic Activity ◽

Etidronic Acid ◽

Resistant Bacteria ◽

Bacterial Cells ◽

Antibiotic Resistant Bacteria ◽

Antibiotic Resistant ◽

Bacterial Membranes ◽

Combined Action

We investigated the combined effects of antimicrobial peptides PG-1 and ChBac3.4 with antiseptics (sodium hypochlorite, dioxidine, prontosan, poviargolum, and etidronic acid) to identify combinations that display synergistic antimicrobial activity against antibiotic-resistant bacteria. We used the checker-board titration method to calculate fractional inhibitory concentration indices, and based on the indices the type of combined action was determined. The combined effect on the metabolic activity of bacteria was evaluated using the fluorescent marker resazurin, and the effect on the permeability of bacterial membranes for chromogenic markers was studied spectrophotometrically. The combined hemolytic activity of the combinations was investigated. Sodium hypochlorite was shown to be antagonistic with both antimicrobial peptides. With other antiseptics, combined action was characterized by additivity or synergy. Synergy was most pronounced with the preparation of highly dispersed silver poviargolum. Antiseptics accelerate the development of the antimicrobial effect of antimicrobial peptides but do not significantly affect the dynamics of the membranolytic action of antimicrobial peptides on bacterial cells. Synergy of hemolytic activity is rare. Thus, the combined use of antimicrobial peptides and antiseptics is promising for combating antibiotic-resistant bacteria and can be used to reduce the toxic effects of these compounds.

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Isolation of a Mycobacteriophage against Mycobacterium smegmatis

European Journal of Biology and Biotechnology ◽

10.24018/ejbio.2021.2.1.147 ◽

2021 ◽

Vol 2 (1) ◽

pp. 34-37

Author(s):

Raquel M. M. Pereira ◽

Hugo V. C. Oliveira ◽

Suanni L. Andrade ◽

Elliot W. Kitajima ◽

Rudi E. L. Procopio

Keyword(s):

Mycobacterium Smegmatis ◽

Human Population ◽

Morphological Analysis ◽

Resistant Bacteria ◽

Bacterial Strains ◽

Antibiotic Resistant ◽

High Incidence ◽

New Antibiotics ◽

Contractile Tail ◽

Amazonas State

The Mycobacterium genus has important pathogenic species, such as M. leprae and M. tuberculosis, with high incidence in the human population. The number of bacterial strains resistant to antibiotics is steadily increasing, and in particular no new antibiotics have been developed for Mycobacterium. Mycobacteriophages have been shown to be viable alternatives, mainly to counteract antibiotic-resistant bacteria. A new mycobacteriophage (Myms-1) was isolated from sewage in Manaus, Amazonas state, Brazil, with lytic activity against M. smegmatis. Morphological analysis of the Mysm-1 phage shows that it probably belongs to the genus Fromanvirus (family Siphoviridae). It has an icosahedral head with approximate diameter of 50 nm and a long non-contractile tail with approximate length of 200 nm. M. smegmatis is a fast-growing mycobacterium found in the environment that is normally non-pathogenic, so it is a promising bacterium for initial tests of this genus.

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Discovering Novel Antimicrobial Peptides in Generative Adversarial Network

10.1101/2021.11.22.469634 ◽

2021 ◽

Author(s):

Tzu-Tang Lin ◽

Li-Yen Yang ◽

Ching-Tien Wang ◽

Ga-Wen Lai ◽

Chi-Fong Ko ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Antibacterial Activities ◽

Resistant Bacteria ◽

Antibacterial Effects ◽

Generative Adversarial Network ◽

Antibiotic Resistant ◽

Adversarial Network ◽

Carbapenem Resistant ◽

Disk Diffusion Testing

Due to the growing number of clinical antibiotic resistance cases in recent years, novel antimicrobial peptides (AMPs) can become ideal for next-generation antibiotics. This study trained a deep convolutional generative adversarial network (GAN) with known AMPs to generate novel AMP candidates. The quality of the GAN-designed peptides was evaluated in silico, and eight of them named GAN-pep 1~8 were chosen to be synthesized for further experiments. Disk diffusion testing and minimum inhibitory concentration (MIC) determination were used to determine the antibacterial effects of the synthesized GAN-designed peptides. Seven out of the eight synthesized GAN-designed peptides showed antibacterial activities. Additionally, GAN-pep 3 and GAN-pep 8 had a broad spectrum of antibacterial effects. Both of them were also effective against antibiotic-resistant bacteria strains such as methicillin-resistant Staphylococcus aureus (S. aureus) and carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa). GAN-pep 3, the most promising GAN-designed peptide candidate, had low MICs against all the tested bacteria.

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